BACKGROUND The treatment of late stages of Legg-Calvé-Perthes disease(LCPD)is controversial.Although the concept of femoral head containment is a well-established technique of treatment,its use remains debatable ...BACKGROUND The treatment of late stages of Legg-Calvé-Perthes disease(LCPD)is controversial.Although the concept of femoral head containment is a well-established technique of treatment,its use remains debatable in the late stages of the disease,as it does not improve symptoms in terms of limb length discrepancy and gait.AIM To assess the results of subtrochanteric valgus osteotomy in symptomatic patients with late-stage Perthes disease.METHODS From 2000 to 2007,36 symptomatic patients with late stage of Perthes disease were surgically treated with subtrochanteric valgus osteotomy and followed-up for 8 to 11 years using the IOWA score and range of motion(ROM)variables.The Mose classification was also assessed at the last follow-up to reflect possible remodeling.The patients were 8 years old or older at the time of surgery,in the post-fragmentation stage,and complaining of pain,limited ROM,Trendelenburg gait,and/or abductor weakness.RESULTS The preoperative IOWA score(average:53.3)markedly improved at the 1-year post follow-up period(average:85.41)and then slightly improved at the last follow-up(average:89.4)(P value<0.05).ROM improved,with internal rotation increased on average by 22°(from 10°preoperatively to 32°postoperatively)and abduction increased on average by 15.9°(from 25°preoperatively to 41°postoperatively).The mean Mose deviation of femoral heads was 4.1 mm at the end of the follow-up period.The tests used were the paired t-test and Pearson correlation test,where the level of significance was a P value less than 0.05.CONCLUSION Subtrochanteric valgus osteotomy can be a good option for symptomatic relief in patients with late-stage of LCPD.展开更多
China’s rural revitalization,which was initiated in the middle and late stages of modernization,features distinct characteristics of the times.It is necessary to approach rural revitalization in China from the aspect...China’s rural revitalization,which was initiated in the middle and late stages of modernization,features distinct characteristics of the times.It is necessary to approach rural revitalization in China from the aspects of industrial-agricultural coordination,urban-rural integration,and regional balance.Industrial-agricultural coordination concerns forging the“world’s factory”and,more importantly,developing into the“world’s farm”through rural revitalization.Urban-rural integration is not just about urban modernization,but also about rural modernization through rural revitalization.Regional balance requires the promotion of characteristic development in peripheral regions with targeted measures of rural revitalization,as well as the building of highly developed city clusters.展开更多
To screen new biological formulations, accurate and efficient application technology, field test was conducted with 72% Bacillus thuringiensis(Bt)·monosultap WP, 8% lambda-cyhalothrin·emamectin benzoate SA a...To screen new biological formulations, accurate and efficient application technology, field test was conducted with 72% Bacillus thuringiensis(Bt)·monosultap WP, 8% lambda-cyhalothrin·emamectin benzoate SA and 3.6% lambda-cyhalothrin·Bt SA through manual spraying and unmanned aerial vehicle spraying. Test results and comprehensive evaluation analysis demonstrated that 72% Bt·monosultap WP and 8%lambda-cyhalothrin·emamectin benzoate SA by manual spraying and unmanned aerial vehicle spraying had good prevention and control effect on strains and internodes damaged by Tryporyza intacta Snellen in middle and late stage, which were ideal new biological formulations with high effi-ciency and low risk for prevention and control of T. intacta in middle and late stage, and could be popularized in sugarcane area. 72% Bt·monosultap WP at the dose of 3 000 g/hectare and 8% lambda-cyhalothrin·emamectin benzoate SA at the dose of 750 mL/hectare could be sprayed in mid September at the peak occurrence period of the forth and fifth generations of T. intacta and Proceras venosatus. Agents were diluted with 900 kg water per hectare, and manually sprayed with electric knapsack sprayer; or agents were diluted with 15 kg of Haoyang aerial control special addi-tives and water per hectare, and sprayed with unmanned aerial vehicle. The control effect against borer-damaged strain rate was above 81.3% and that against borer-damaged internode rate was above 88.6%.展开更多
OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in at...OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side effects.METHODS A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side effect.Comparative oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer carcinogenesis.RESULTS Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week 3.Both D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound treatment.Notably,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma cells.CONCLUSION Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of oxylipins.This study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.展开更多
Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulati...Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.展开更多
BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identif...BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.展开更多
Objective: To study the safety and efficacy of concurrent bilateral total knee arthroplasty orstaged bilateral total knee replacement using meta-analysis. Methods: The databases of ChinaWanfang, CNKI, PubMed, Cochrane...Objective: To study the safety and efficacy of concurrent bilateral total knee arthroplasty orstaged bilateral total knee replacement using meta-analysis. Methods: The databases of ChinaWanfang, CNKI, PubMed, Cochrane Library, and Web of Science were searched conducted formeta-analysis of the extracted data using Review Manager 5.3 software. Results: ①A total of 18retrospective cohort studies were included, 72 831 patients in the same period group and 103595 patients in the staging group. ②The results of meta showed that in the staging group, theincidence of postoperative cardiac complications[OR= 1.21, 95%CI=(1.10~1.34), P<0.000 1] ,neurological complications[OR=1.67, 95%CI=(1.29~2.16), P<0.000 1], deep vein thrombosis[OR=1.38, 95%CI(1.27~1.50), P<0.000 01], mortality[OR=2.18, 95%CI=(1.67~2.84),P<0.000 01] and perioperative blood loss [OR=246.75, 95%CI=(233.30~260.20)] were lessthan those in the same period group (P<0.000 01);The postoperative deep infection rate in thesame period group [OR=0.61, 95%CI=(0.52~0.71), P<0.000 01] was lower than that in thestaging group;The postoperative superficial infection rate [OR=0.96, 95%CI=(0.66~1.40)],revision rate of joint replacement [OR= 1.04, 95%CI=( 0.96~1.12)], HSS score [OR=0.10,95%CI=(-0.61~0.80), P=0.79] and knee joint activity score [OR=-0.23, 95%CI=(-1.25~0.78)]were not statistically significant between the two groups(P>0.05).Conclusion: Stagingbilateral total knee replacement can more effectively reduce the incidence of perioperativecomplications and reduce the amount of blood transfusion, while concurrent bilateral total kneereplacement can reduce the rate of deep infection. To further compare the efficacy and safety ofconcurrent or staged bilateral total knee arthroplasty, further studies must be conducted in theform of a randomized clinical trial to evaluate the results mentioned in this meta-analysis.展开更多
The Early Paleozoic tectono-thermal event was a significant orogenic activity during the Phanerozoic era,which had a profound impact on the early crust of the South China Block(SCB) and established the foundation for ...The Early Paleozoic tectono-thermal event was a significant orogenic activity during the Phanerozoic era,which had a profound impact on the early crust of the South China Block(SCB) and established the foundation for later tectonic activity.The Wuyi-Yunkai orogenic belt in Southeastern China was extensively exposed to Early Paleozoic magmatism,the genetic mechanism of which remains controversial.To shed light on this issue,detailed petrological,geochemical,and zircon U-Pb-Hf isotopic studies were carried out on two granitoids,namely the Yuntongshan pluton and the Gaoqiao pluton,identified in the central Wuyishan.Zircon U-Pb chronology of the Yuntongshan and Gaoqiao bodies yielded ages of437±4 Ma(MSWD=2.2) and 404±2 Ma(MSWD=12),respectively,indicating that they were emplaced during the Early Silurian and Early Devonian periods.These granitoids are primarily composed of biotite-granite and biotite-monzonitic-granites,with high concentrations of S_(i)O_(2)(73.59-75.91 wt%),K_(2)O+Na_(2)O(8.31-8.73wt%),and low contents of MgO,CaO,Cr,Ni.They are classified as high-K calc-alkaline and weakly metaluminous-strongly peraluminous S-type granites.These granitoids are enriched in light rare earth elements(LREEs) and large ion lithophile elements(LILEs) and depleted in heavy rare earth elements(HREEs) and high field strength elements(HFSEs) with arc affinity.The εHf(t) values of-3.3 to-15.4 with two-stage Hf model ages ranging from 2829 to 1644 Ma,combined with the presence of Neoproterozoic inherited zircons,suggest that the primary magma of these granitoids was derived from the partial melting of Neoproterozoic crust with a Paleoproterozoic crustal model age.These findings,combined with the spatio-temporal distribution of regional magmatism,reveal that the late Early-Paleozoic granitoids formed in the intraplate orogenic background originating from the subduction of the proto-Tethys Ocean and proto-Pacific Ocean around the margin of the east Gondwana supercontinent.展开更多
Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16...Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.展开更多
The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding...The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.展开更多
Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: E...Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.展开更多
BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of...BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.展开更多
BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,som...BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.展开更多
BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emot...BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.展开更多
BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there ar...BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.展开更多
Objective:To analyze the different clinical features of patients with early-onset(EO-NMOSDs)and late-onset neuromyelitis optica spectrum diseases(LO-NMOSDs).Methods:A total of 51patients with neuromyelitis optica spec...Objective:To analyze the different clinical features of patients with early-onset(EO-NMOSDs)and late-onset neuromyelitis optica spectrum diseases(LO-NMOSDs).Methods:A total of 51patients with neuromyelitis optica spectrum disease who were diagnosed in our hospital for the first time from January 2015 to December 2022 were included in the First Affiliated Hospital of Hainan Medical College and divided into 22 cases in the EO-NMOSDs group and 29 cases in the LO-NMOSDs group according to whether the age of onset was 50 years old.The basic data,Extended Disability Status Scale(EDSS)score,blood and cerebrospinal fluid test indicators of the two groups were statistically analyzed.Results:There were no significant differences in demographic characteristics,clinical features and serum AQP-4 antibody positivity rate between the two groups(all P>0.05),and there were significant differences in triglycerides(TG),low-density lipoprotein(LDL),apolipoprotein A(APOA),apolipoprotein B(APOB)and lipoprotein a(P=0.010,P=0.048,P=0.014,P=0.061,P=0.001,respectively),and cerebrospinal fluid LDH,There were significant differences between microprotein quantification and EDSS score(P=0.018,P=0.034,P=0.025,respectively),and the level of microprotein quantification in cerebrospinal fluid of LO-NMOSDs had a certain correlation with the degree of disability(r=0.52,P<0.03).Conclusion:LO-NMOSDs and EO-NMOSDs group patients have similar demographic characteristics,serum AQP-4 antibody positive rate and clinical features,but compared with EO-NMOSDs,patients in LO-NMOSDs group are prone to abnormal lipid metabolism,higher trace proteins in cerebrospinal fluid and more likely to be disabled,and among LO-NMOSDs,the higher the trace protein in the cerebrospinal fluid,the more severe the disability status of patients.展开更多
BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource utilization.As degenerative conditions progress in multiple joints,many p...BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource utilization.As degenerative conditions progress in multiple joints,many patients undergo multiple proce-dures.AIM To determine if both physicians and patients learn from the patient’s initial arth-roplasty,resulting in improved outcomes following the second procedure.METHODS The institutional database was retrospectively queried for primary total hip arth-roplasty(THA)and total knee arthroplasty(TKA).Patients with only unilateral THA or TKA,and patients undergoing same-day bilateral TJA,were excluded.Patient demographics,comorbidities,and implant sizes were collected at the time of each procedure and patients were stratified by first vs second surgery.Outcome metrics evaluated included operative time,length of stay(LOS),disposition,90-d readmissions and emergency department(ED)visits.RESULTS A total of 642 patients,including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA,were analyzed.There was no significant difference in demographics or comorbidities between the first and second procedure,which were separated by a mean of 285 d.For THA and TKA,LOS was significantly less for the second surgery,with 66%of patients having a shorter hospitalization(P<0.001).THA patients had significantly decreased operative time only when the same sized implant was utilized(P=0.025).The vast majority(93.3%)of patients were discharged to the same type of location following their second surgery.However,when a change in disposition was present from the first surgery,patients were significantly more likely to be discharged to home after the second procedure(P=0.033).There was no difference between procedures for post-operative readmissions(P=0.438)or ED visits(P=0.915).CONCLUSION After gaining valuable experience recovering from the initial surgery,a patient’s perioperative outcomes are improved for their second TJA.This may be the result of increased confidence and decreased anxiety,and it supports the theory that enhanced patient education pre-operatively may improve outcomes.For the surgical team,the second procedure of a staged THA is more efficient,although this finding did not hold for TKA.展开更多
Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is ...Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.展开更多
American Hollywood animated films have conquered the world.In recent years,many successful works have appeared in domestic animated films,bringing new vitality to the Chinese animated film industry.Based on Lacan’s M...American Hollywood animated films have conquered the world.In recent years,many successful works have appeared in domestic animated films,bringing new vitality to the Chinese animated film industry.Based on Lacan’s Mirror Stage Theory,this study attempts to start from the bravery of Judy and Nezha,the protagonists of Zootopia(2016)and Nezha(2019).It analyzes and compares their embodiment,formation,influence and reflection with real society to solve the problems of the two brave characters’formation causes,characteristic differences and social influences,including racial discrimination,individualism in American society and family problems in Chinese society.This study sheds light on the transmission of intercultural values in animated films.展开更多
Objective:To evaluate the effect and efficiency of ear tip bloodletting combined with Xianfang Huoming Yin(XFH)in the treatment of early-stage wheals.Methods:70 patients with early-stage wheals admitted from September...Objective:To evaluate the effect and efficiency of ear tip bloodletting combined with Xianfang Huoming Yin(XFH)in the treatment of early-stage wheals.Methods:70 patients with early-stage wheals admitted from September 2020 to September 2022 were divided into two groups by randomized numerical table method,with 35 cases/group.Both groups received conventional treatment,the control group combined with XFH,and the observation group combined with ear tip bloodletting therapy and XFH.Conscious symptom scores,ocular indexes,therapeutic effects,and sleep quality between the two groups were compared.Results:After the treatment,the patients in the observation group had lower self-awareness symptom scores and sleep quality scores as compared to those in the control group;the diameter of the mass in the observation group was smaller than that of the control group after treatment;the average tear film rupture time and the time taken for the first non-contact tear film to rupture were longer in the observation group than those in the control group;the total effective rate of the treatment in the observation group was higher than that of the control group(P<0.05).Conclusion:Ear tip bloodletting combined with XFH was ideal for the treatment of early-stage wheals and has a high effective rate.展开更多
文摘BACKGROUND The treatment of late stages of Legg-Calvé-Perthes disease(LCPD)is controversial.Although the concept of femoral head containment is a well-established technique of treatment,its use remains debatable in the late stages of the disease,as it does not improve symptoms in terms of limb length discrepancy and gait.AIM To assess the results of subtrochanteric valgus osteotomy in symptomatic patients with late-stage Perthes disease.METHODS From 2000 to 2007,36 symptomatic patients with late stage of Perthes disease were surgically treated with subtrochanteric valgus osteotomy and followed-up for 8 to 11 years using the IOWA score and range of motion(ROM)variables.The Mose classification was also assessed at the last follow-up to reflect possible remodeling.The patients were 8 years old or older at the time of surgery,in the post-fragmentation stage,and complaining of pain,limited ROM,Trendelenburg gait,and/or abductor weakness.RESULTS The preoperative IOWA score(average:53.3)markedly improved at the 1-year post follow-up period(average:85.41)and then slightly improved at the last follow-up(average:89.4)(P value<0.05).ROM improved,with internal rotation increased on average by 22°(from 10°preoperatively to 32°postoperatively)and abduction increased on average by 15.9°(from 25°preoperatively to 41°postoperatively).The mean Mose deviation of femoral heads was 4.1 mm at the end of the follow-up period.The tests used were the paired t-test and Pearson correlation test,where the level of significance was a P value less than 0.05.CONCLUSION Subtrochanteric valgus osteotomy can be a good option for symptomatic relief in patients with late-stage of LCPD.
基金This paper is a phased research result of“studies on the outstanding problems with rural development and corresponding countermeasures during the decisive stage in building a moderately prosperous society in all respects”(16JJD810003),a major project of the Key Research Base for Humanities and Social Sciences of the Ministry of Education of the People’s Republic of China.
文摘China’s rural revitalization,which was initiated in the middle and late stages of modernization,features distinct characteristics of the times.It is necessary to approach rural revitalization in China from the aspects of industrial-agricultural coordination,urban-rural integration,and regional balance.Industrial-agricultural coordination concerns forging the“world’s factory”and,more importantly,developing into the“world’s farm”through rural revitalization.Urban-rural integration is not just about urban modernization,but also about rural modernization through rural revitalization.Regional balance requires the promotion of characteristic development in peripheral regions with targeted measures of rural revitalization,as well as the building of highly developed city clusters.
基金Supported by Special Fund of China Agricultural (Sugar) Industry Research System(CARS-170303)Training Project of Yunling Industry and Technology Leading Talents "Control of Sugarcane Harm-ful Organisms"(2018LJRC56)Special Fund of Agricultural Industry Research System in Yunnan Province
文摘To screen new biological formulations, accurate and efficient application technology, field test was conducted with 72% Bacillus thuringiensis(Bt)·monosultap WP, 8% lambda-cyhalothrin·emamectin benzoate SA and 3.6% lambda-cyhalothrin·Bt SA through manual spraying and unmanned aerial vehicle spraying. Test results and comprehensive evaluation analysis demonstrated that 72% Bt·monosultap WP and 8%lambda-cyhalothrin·emamectin benzoate SA by manual spraying and unmanned aerial vehicle spraying had good prevention and control effect on strains and internodes damaged by Tryporyza intacta Snellen in middle and late stage, which were ideal new biological formulations with high effi-ciency and low risk for prevention and control of T. intacta in middle and late stage, and could be popularized in sugarcane area. 72% Bt·monosultap WP at the dose of 3 000 g/hectare and 8% lambda-cyhalothrin·emamectin benzoate SA at the dose of 750 mL/hectare could be sprayed in mid September at the peak occurrence period of the forth and fifth generations of T. intacta and Proceras venosatus. Agents were diluted with 900 kg water per hectare, and manually sprayed with electric knapsack sprayer; or agents were diluted with 15 kg of Haoyang aerial control special addi-tives and water per hectare, and sprayed with unmanned aerial vehicle. The control effect against borer-damaged strain rate was above 81.3% and that against borer-damaged internode rate was above 88.6%.
基金The project supported by a research grant from Ministry of Science and Technology(MOST 103-2320-B-001-008-MY3),Chinese Taipei
文摘OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side effects.METHODS A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side effect.Comparative oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer carcinogenesis.RESULTS Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week 3.Both D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound treatment.Notably,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma cells.CONCLUSION Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of oxylipins.This study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.
基金financially supported grants from National Natural Science Foundation of China(Grant Nos.31902053,31870279,31730081)China Postdoctoral Science Foundation(Grant No.2018M642273)+3 种基金Jiangsu Planned Projects or Postdoctoral Reaearch Funds(Grant No.2019K169)the Fundamental Research Funds for the Central Uniersities(Grant No.KYQN202031)the National Key Research and Development Program of China(Grant Nos.2019YFD1001500,2020YFD1000400)the earmarked fund for Jiangsu Agricultural Industry Technology System,and a project funded by the Priority academic Program Development of Jiangsu Higher Education Institutions。
文摘Color fading caused by a decrease in anthocyanin accumulation during the post-flowering stage significantly affects postharvest quality of chrysanthemum.However,the underlying mechanism by which anthocyanin accumulation decreases during the post-flowering stage still unclear,which greatly restricts design of molecular breeding in chrysanthemum.Here,a chrysanthemum SG7 R2R3 MYB transcription factor(TF),CmMYB3-like,was identified to have a function in regulating anthocyanin biosynthesis during the post-flowering stage.Quantitative real time PCR(qRT-PCR)assays showed that the expression of CmMYB3-like was gradually downregulated when anthocyanin content increased during the flowering stage and was significantly upregulated during the post-flowering stage.Genetic transformation of chrysanthemum and dual-luciferase assays in N.benthamiana leaves showed that CmMYB3-like suppressed anthocyanin accumulation by inhibiting the transcription of CmCHS and CmANS directly and that of CmF3H indirectly.However,overexpression or suppression of CmMYB3-like did not affect the biosynthesis of flavones or flavonols.Genetic transformation of chrysanthemum revealed that the overexpression of CmMYB3-like inhibited anthocyanin accumulation,but its suppression prevented the decrease in anthocyanin accumulation during the post-flowering stage.Our results revealed a crucial role of CmMYB3-like in regulating the color of petals during the post-flowering stage and provided a target gene for molecular design breeding to improve the postharvest quality of chrysanthemum.
基金Supported by the National Natural Science foundation of China,No.82202135,82371919,82372017,and 82171925China Postdoctoral Science Foundation,No.2023M741808+3 种基金Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology,No.JSTJ-2023-WJ027Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine,No.2023QB0112Nanjing Postdoctoral Science Foundation,Natural Science Foundation of Nanjing University of Chinese Medicine,No.XZR2023036 and XZR2021050Medical Imaging Artificial Intelligence Special Research Fund Project,Nanjing Medical Association Radiology Branch,Project of National Clinical Research Base of Traditional Chinese Medicine in Jiangsu Province,China,No.JD2023SZ16.
文摘BACKGROUND One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma(PDAC)is that most patients are usually diagnosed at late stages.There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages.METHODS A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography(CT)within 30 d prior to surgery were included in the study.Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system.Radiomics features were extracted from the region of interest(ROI)for each patient using Analysis Kit software.The most important and predictive radiomics features were selected using Mann-Whitney U test,univar-iate logistic regression analysis,and minimum redundancy maximum relevance(MRMR)method.Random forest(RF)method was used to construct the radiomics model,and 10-times leave group out cross-validation(LGOCV)method was used to validate the robustness and reproducibility of the model.RESULTS A total of 792 radiomics features(396 from late arterial phase and 396 from portal venous phase)were extracted from the ROI for each patient using Analysis Kit software.Nine most important and predictive features were selected using Mann-Whitney U test,univariate logistic regression analysis,and MRMR method.RF method was used to construct the radiomics model with the nine most predictive radiomics features,which showed a high discriminative ability with 97.7%accuracy,97.6%sensitivity,97.8%specificity,98.4%positive predictive value,and 96.8%negative predictive value.The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models.CONCLUSION The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2019D01C244)。
文摘Objective: To study the safety and efficacy of concurrent bilateral total knee arthroplasty orstaged bilateral total knee replacement using meta-analysis. Methods: The databases of ChinaWanfang, CNKI, PubMed, Cochrane Library, and Web of Science were searched conducted formeta-analysis of the extracted data using Review Manager 5.3 software. Results: ①A total of 18retrospective cohort studies were included, 72 831 patients in the same period group and 103595 patients in the staging group. ②The results of meta showed that in the staging group, theincidence of postoperative cardiac complications[OR= 1.21, 95%CI=(1.10~1.34), P<0.000 1] ,neurological complications[OR=1.67, 95%CI=(1.29~2.16), P<0.000 1], deep vein thrombosis[OR=1.38, 95%CI(1.27~1.50), P<0.000 01], mortality[OR=2.18, 95%CI=(1.67~2.84),P<0.000 01] and perioperative blood loss [OR=246.75, 95%CI=(233.30~260.20)] were lessthan those in the same period group (P<0.000 01);The postoperative deep infection rate in thesame period group [OR=0.61, 95%CI=(0.52~0.71), P<0.000 01] was lower than that in thestaging group;The postoperative superficial infection rate [OR=0.96, 95%CI=(0.66~1.40)],revision rate of joint replacement [OR= 1.04, 95%CI=( 0.96~1.12)], HSS score [OR=0.10,95%CI=(-0.61~0.80), P=0.79] and knee joint activity score [OR=-0.23, 95%CI=(-1.25~0.78)]were not statistically significant between the two groups(P>0.05).Conclusion: Stagingbilateral total knee replacement can more effectively reduce the incidence of perioperativecomplications and reduce the amount of blood transfusion, while concurrent bilateral total kneereplacement can reduce the rate of deep infection. To further compare the efficacy and safety ofconcurrent or staged bilateral total knee arthroplasty, further studies must be conducted in theform of a randomized clinical trial to evaluate the results mentioned in this meta-analysis.
基金supported by the National Natural Science Foundation of China (No.41702204)the Central Fundamental Research (grant number DZLXJK201504)the Major State Research Development Program of China (grant number 2016YFC0600202)。
文摘The Early Paleozoic tectono-thermal event was a significant orogenic activity during the Phanerozoic era,which had a profound impact on the early crust of the South China Block(SCB) and established the foundation for later tectonic activity.The Wuyi-Yunkai orogenic belt in Southeastern China was extensively exposed to Early Paleozoic magmatism,the genetic mechanism of which remains controversial.To shed light on this issue,detailed petrological,geochemical,and zircon U-Pb-Hf isotopic studies were carried out on two granitoids,namely the Yuntongshan pluton and the Gaoqiao pluton,identified in the central Wuyishan.Zircon U-Pb chronology of the Yuntongshan and Gaoqiao bodies yielded ages of437±4 Ma(MSWD=2.2) and 404±2 Ma(MSWD=12),respectively,indicating that they were emplaced during the Early Silurian and Early Devonian periods.These granitoids are primarily composed of biotite-granite and biotite-monzonitic-granites,with high concentrations of S_(i)O_(2)(73.59-75.91 wt%),K_(2)O+Na_(2)O(8.31-8.73wt%),and low contents of MgO,CaO,Cr,Ni.They are classified as high-K calc-alkaline and weakly metaluminous-strongly peraluminous S-type granites.These granitoids are enriched in light rare earth elements(LREEs) and large ion lithophile elements(LILEs) and depleted in heavy rare earth elements(HREEs) and high field strength elements(HFSEs) with arc affinity.The εHf(t) values of-3.3 to-15.4 with two-stage Hf model ages ranging from 2829 to 1644 Ma,combined with the presence of Neoproterozoic inherited zircons,suggest that the primary magma of these granitoids was derived from the partial melting of Neoproterozoic crust with a Paleoproterozoic crustal model age.These findings,combined with the spatio-temporal distribution of regional magmatism,reveal that the late Early-Paleozoic granitoids formed in the intraplate orogenic background originating from the subduction of the proto-Tethys Ocean and proto-Pacific Ocean around the margin of the east Gondwana supercontinent.
基金This study was supported by the National Water Pollution Control and Treatment Science and Technology Major Project(2017ZX07101-002).
文摘Tree interactions are essential for the structure,dynamics,and function of forest ecosystems,but variations in the architecture of life-stage interaction networks(LSINs)across forests is unclear.Here,we constructed 16 LSINs in the mountainous forests of northwest Hebei,China based on crown overlap from four mixed forests with two dominant tree species.Our results show that LSINs decrease the complexity of stand densities and basal areas due to the interaction cluster differentiation.In addition,we found that mature trees and saplings play different roles,the first acting as“hub”life stages with high connectivity and the second,as“bridges”controlling information flow with high centrality.Across the forests,life stages with higher importance showed better parameter stability within LSINs.These results reveal that the structure of tree interactions among life stages is highly related to stand variables.Our efforts contribute to the understanding of LSIN complexity and provide a basis for further research on tree interactions in complex forest communities.
基金supported by the National Natural Science Foundation of China(31790410,32160781)。
文摘The gastrointestinal tract is essential for food digestion,nutrient absorption,waste elimination,and microbial defense.Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity,functional heterogeneity,and their importance in intestinal tract development and disease.Although such profiling has been extensively conducted in humans and mice,the single-cell gene expression landscape of the pig cecum remains unexplored.Here,single-cell RNA sequencing was performed on 45572 cells obtained from seven cecal samples in pigs at four different developmental stages(days(D)30,42,150,and 730).Analysis revealed 12 major cell types and 38 subtypes,as well as their distinctive genes,transcription factors,and regulons,many of which were conserved in humans.An increase in the relative proportions of CD8^(+)T and Granzyme A(low expression)natural killer T cells(GZMA^(low)NKT)cells and a decrease in the relative proportions of epithelial stem cells,Tregs,RHEX^(+)T cells,and plasmacytoid dendritic cells(pDCs)were noted across the developmental stages.Moreover,the post-weaning period exhibited an up-regulation in mitochondrial genes,COX2 and ND2,as well as genes involved in immune activation in multiple cell types.Cell-cell crosstalk analysis indicated that IBP6^(+)fibroblasts were the main signal senders at D30,whereas IBP6^(−)fibroblasts assumed this role at the other stages.NKT cells established interactions with epithelial cells and IBP6^(+)fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs.This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.
文摘Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.
基金the Foundation for Cancer Research supported by Kyoto Preventive Medical Center and the Japan Society for the Promotion of Science(JSPS)Grants-in-Aid KAKENHI,No.JP 22K21080.
文摘BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor prognoses.The efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside screening.Although identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less appreciated.In the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related symptoms.AIM To clarify the stage at CRC diagnosis based on diagnostic routes.METHODS We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two hospitals.The diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and symptomatic.The early-stage was defined as Stages 0 or I.Multivariate and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up group.The adjusted covariates were age,sex,and tumor location.RESULTS Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,respectively.Among the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,respectively.The symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening groups(P=0.493,aOR for early-stage diagnosis in the cancer screening group vs follow-up group=1.11;95%CI=0.82-1.49).CONCLUSION CRCs detected during hospital visits for comorbidities were diagnosed earlier,similar to cancer screening.CRC screening should be recommended,particularly for patients without periodical hospital visits for comorbidities.
基金Supported by the Science and Technology Planning Project of Guangdong Province,China,No.2019B0202280015010 Project of Sun Yatsen University,No.2018024Science and Technology Program of Guangzhou,China,No.202103000060.
文摘BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.
基金Supported by The National Natural Science Foundation of China,No.81871080the Key R&D Program of Jining(Major Program),No.2023YXNS004+2 种基金the National Natural Science Foundation of China,No.81401486the Natural Science Foundation of Liaoning Province of China,No.20170540276the Medicine and Health Science Technology Development Program of Shandong Province,No.202003070713.
文摘BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.
基金Supported by the National Natural Science Foundation of China,No.82020108031,No.81973398,and No.82104290Guangdong Provincial Key Laboratory of Construction Foundation,No.2020B1212060034Guangdong Basic and Applied Basic Research Foundation,No.2022A1515012549 and No.2023A1515012667.
文摘BACKGROUND Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines.Dose optimization guided by nudix hydrolase 15(NUDT15)has significantly reduced the early leucopenia rate,but there are no definitive biomarkers for late risk leucopenia prediction.AIM To determine the predictive value of early monitoring of DNA-thioguanine(DNATG)or 6-thioguanine nucleotides(6TGN)for late leucopenia under a NUDT15-guided thiopurine dosing strategy in patients with Crohn’s disease(CD).METHODS Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations.Late leucopenia was defined as a leukocyte count<3.5×10^(9)/L over two months.RESULTS Of 148 patients studied,late leucopenia was observed in 15.6%(17/109)of NUDT15/thiopurine methyltransferase(TPMT)normal and 64.1%(25/39)of intermediate metabolizers.In patients suffering late leucopenia,early DNATG levels were significantly higher than in those who did not develop late leucopenia(P=4.9×10^(-13)).The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve(AUC)of 0.855(sensitivity 83%,specificity 81%),and in NUDT15/TPMT normal metabolizers,the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902(sensitivity 88%,specificity 85%).6TGN had a relatively poor correlation with late leucopenia whether in the entire sample(P=0.021)or NUDT15/TPMT normal or intermediate metabolizers(P=0.018,P=0.55,respectively).CONCLUSION Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both NUDT15/TPMT normal and intermediate metabolizers with CD,especially the former.
基金Hainan Clinical Medicine Center Construction Project(2021)Hainan Provincial Excellent Talent Team(QRCBT202121)Key R&D Plan of Hainan Province(ZDYF2022SHFZ109)。
文摘Objective:To analyze the different clinical features of patients with early-onset(EO-NMOSDs)and late-onset neuromyelitis optica spectrum diseases(LO-NMOSDs).Methods:A total of 51patients with neuromyelitis optica spectrum disease who were diagnosed in our hospital for the first time from January 2015 to December 2022 were included in the First Affiliated Hospital of Hainan Medical College and divided into 22 cases in the EO-NMOSDs group and 29 cases in the LO-NMOSDs group according to whether the age of onset was 50 years old.The basic data,Extended Disability Status Scale(EDSS)score,blood and cerebrospinal fluid test indicators of the two groups were statistically analyzed.Results:There were no significant differences in demographic characteristics,clinical features and serum AQP-4 antibody positivity rate between the two groups(all P>0.05),and there were significant differences in triglycerides(TG),low-density lipoprotein(LDL),apolipoprotein A(APOA),apolipoprotein B(APOB)and lipoprotein a(P=0.010,P=0.048,P=0.014,P=0.061,P=0.001,respectively),and cerebrospinal fluid LDH,There were significant differences between microprotein quantification and EDSS score(P=0.018,P=0.034,P=0.025,respectively),and the level of microprotein quantification in cerebrospinal fluid of LO-NMOSDs had a certain correlation with the degree of disability(r=0.52,P<0.03).Conclusion:LO-NMOSDs and EO-NMOSDs group patients have similar demographic characteristics,serum AQP-4 antibody positive rate and clinical features,but compared with EO-NMOSDs,patients in LO-NMOSDs group are prone to abnormal lipid metabolism,higher trace proteins in cerebrospinal fluid and more likely to be disabled,and among LO-NMOSDs,the higher the trace protein in the cerebrospinal fluid,the more severe the disability status of patients.
文摘BACKGROUND With the increasing incidence of total joint arthroplasty(TJA),there is a desire to reduce peri-operative complications and resource utilization.As degenerative conditions progress in multiple joints,many patients undergo multiple proce-dures.AIM To determine if both physicians and patients learn from the patient’s initial arth-roplasty,resulting in improved outcomes following the second procedure.METHODS The institutional database was retrospectively queried for primary total hip arth-roplasty(THA)and total knee arthroplasty(TKA).Patients with only unilateral THA or TKA,and patients undergoing same-day bilateral TJA,were excluded.Patient demographics,comorbidities,and implant sizes were collected at the time of each procedure and patients were stratified by first vs second surgery.Outcome metrics evaluated included operative time,length of stay(LOS),disposition,90-d readmissions and emergency department(ED)visits.RESULTS A total of 642 patients,including 364 undergoing staged bilateral TKA and 278 undergoing bilateral THA,were analyzed.There was no significant difference in demographics or comorbidities between the first and second procedure,which were separated by a mean of 285 d.For THA and TKA,LOS was significantly less for the second surgery,with 66%of patients having a shorter hospitalization(P<0.001).THA patients had significantly decreased operative time only when the same sized implant was utilized(P=0.025).The vast majority(93.3%)of patients were discharged to the same type of location following their second surgery.However,when a change in disposition was present from the first surgery,patients were significantly more likely to be discharged to home after the second procedure(P=0.033).There was no difference between procedures for post-operative readmissions(P=0.438)or ED visits(P=0.915).CONCLUSION After gaining valuable experience recovering from the initial surgery,a patient’s perioperative outcomes are improved for their second TJA.This may be the result of increased confidence and decreased anxiety,and it supports the theory that enhanced patient education pre-operatively may improve outcomes.For the surgical team,the second procedure of a staged THA is more efficient,although this finding did not hold for TKA.
基金supported by NIH Grants R01NS092651 and R21NS111275-01the Department of Veterans Affairs,BX001148 and BX005899(to PHK)。
文摘Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.
文摘American Hollywood animated films have conquered the world.In recent years,many successful works have appeared in domestic animated films,bringing new vitality to the Chinese animated film industry.Based on Lacan’s Mirror Stage Theory,this study attempts to start from the bravery of Judy and Nezha,the protagonists of Zootopia(2016)and Nezha(2019).It analyzes and compares their embodiment,formation,influence and reflection with real society to solve the problems of the two brave characters’formation causes,characteristic differences and social influences,including racial discrimination,individualism in American society and family problems in Chinese society.This study sheds light on the transmission of intercultural values in animated films.
文摘Objective:To evaluate the effect and efficiency of ear tip bloodletting combined with Xianfang Huoming Yin(XFH)in the treatment of early-stage wheals.Methods:70 patients with early-stage wheals admitted from September 2020 to September 2022 were divided into two groups by randomized numerical table method,with 35 cases/group.Both groups received conventional treatment,the control group combined with XFH,and the observation group combined with ear tip bloodletting therapy and XFH.Conscious symptom scores,ocular indexes,therapeutic effects,and sleep quality between the two groups were compared.Results:After the treatment,the patients in the observation group had lower self-awareness symptom scores and sleep quality scores as compared to those in the control group;the diameter of the mass in the observation group was smaller than that of the control group after treatment;the average tear film rupture time and the time taken for the first non-contact tear film to rupture were longer in the observation group than those in the control group;the total effective rate of the treatment in the observation group was higher than that of the control group(P<0.05).Conclusion:Ear tip bloodletting combined with XFH was ideal for the treatment of early-stage wheals and has a high effective rate.
