The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal ...The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.展开更多
BACKGROUND The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis(HS)in children.We also hope to ...BACKGROUND The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis(HS)in children.We also hope to promote the application of gene detection technology in children with HS,with the goals of identifying more related gene mutations,supporting the acquisition of improved molecular genetic information to further reveal the pathogenesis of HS in children,and providing important guidance for the diagnosis,treatment,and prevention of HS in children.CASE SUMMARY A 1-year and 5-month-old patient presented jaundice during the neonatal period,mild anemia 8 months later,splenic enlargement at 1 year and 5 months,and brittle red blood cell permeability.Genetic testing was performed on the patient,their parents,and sister.Swiss Model software was used to predict the protein structure of complex heterozygous mutations in ANK1 and SPTA1.Genetic testing revealed that the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother.Combined with the clinical symptoms of the children,it is suggested that the newly discovered complex heterozygous mutations of ANK1 and SPTA1 may be the cause,providing important guidance for revealing the pathogenesis,diagnosis,treatment,and promotion of gene detection technology in children with HS.CONCLUSION This case involves an unreported complex heterozygous mutation of ANK1 and SPTA1,which provides a reference for exploring HS.展开更多
One of the open problems in the field of forward uncertainty quantification(UQ)is the ability to form accurate assessments of uncertainty having only incomplete information about the distribution of random inputs.Anot...One of the open problems in the field of forward uncertainty quantification(UQ)is the ability to form accurate assessments of uncertainty having only incomplete information about the distribution of random inputs.Another challenge is to efficiently make use of limited training data for UQ predictions of complex engineering problems,particularly with high dimensional random parameters.We address these challenges by combining data-driven polynomial chaos expansions with a recently developed preconditioned sparse approximation approach for UQ problems.The first task in this two-step process is to employ the procedure developed in[1]to construct an"arbitrary"polynomial chaos expansion basis using a finite number of statistical moments of the random inputs.The second step is a novel procedure to effect sparse approximation via l1 minimization in order to quantify the forward uncertainty.To enhance the performance of the preconditioned l1 minimization problem,we sample from the so-called induced distribution,instead of using Monte Carlo(MC)sampling from the original,unknown probability measure.We demonstrate on test problems that induced sampling is a competitive and often better choice compared with sampling from asymptotically optimal measures(such as the equilibrium measure)when we have incomplete information about the distribution.We demonstrate the capacity of the proposed induced sampling algorithm via sparse representation with limited data on test functions,and on a Kirchoff plating bending problem with random Young’s modulus.展开更多
Six outcrop sections in Fenghe River,Northwestern China,were sampled and analyzed.This study aims to determine provenance,tectonic setting,and source-area paleoweathering of the sediments of Fenghe River in combinatio...Six outcrop sections in Fenghe River,Northwestern China,were sampled and analyzed.This study aims to determine provenance,tectonic setting,and source-area paleoweathering of the sediments of Fenghe River in combination of lithofacies analysis and bulk-rock geochemical data.The lithofacies in the studied area were classified as gravel,sand,and fine-grained clastic lithofacies,reflecting generally channel fill deposits,channel bar deposits,and over-bank deposits,respectively.The Chemical Index of Alteration(CIA),Plagioclase Index of Alteration(PIA),and Chemical Index of Weathering(CIW)values ranged 50.10–62.29,50.13–66.35,56.52–71.12,respectively,together with element ratios such as Rb/Sr,K/Na,Rb/K,Th/K,Rb/Ti,and Cs/Ti indicate that the source area was under a low to moderate chemical weathering condition probably in cold and semi-arid climates.Moreover,plot of SiO_(2)vs.(Al_(2)O_(3)+K_(2)O+Na_(2)O)suggests that the sediments were deposited in a semi-arid climate.Plots of Cr/Th vs.Th/Sc,TiO_(2)vs.Zr,La/Yb vs.rare earth element(REE),and La-Th-Sc ternary diagrams,along with the lithology,indicate that the sediments in Fenghe River were mainly originated from felsic igneous rocks.Major elements-based discrimination diagrams and Th-Sc-Zr/10 and La-Th-Sc ternary diagram of the samples indicates that the source rocks of Fenghe River developed in a composite active continental margin and continental island arc field.展开更多
Endochondral ossification requires proper control of chondrocyte proliferation,differentiation,survival,and organization.Here we show that knockout ofα-parvin,an integrin-associated focal adhesion protein,from murine...Endochondral ossification requires proper control of chondrocyte proliferation,differentiation,survival,and organization.Here we show that knockout ofα-parvin,an integrin-associated focal adhesion protein,from murine limbs causes defects in endochondral ossification and dwarfism.The mutant long bones were shorter but wider,and the growth plates became disorganized,especially in the proliferative zone.With two-photon time-lapse imaging of bone explant culture,we provide direct evidence showing thatα-parvin regulates chondrocyte rotation,a process essential for chondrocytes to form columnar structure.Furthermore,loss ofα-parvin increased binucleation,elevated cell death,and caused dilation of the resting zones of mature growth plates.Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones(i.e.,resting,proliferative,and hypertrophic zones)of the growth plates.Our results demonstrate a crucial role ofα-parvin in long bone development and shed light on the cellular mechanism through whichα-parvin regulates the longitudinal growth of long bones.展开更多
Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes aff...Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival(OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio(HR)=0.9, P=0.529]; this risk was 60% lower than that of the group undergoing supportive treatment(HR=0.4, P=0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy(HR=2.3, P<0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.展开更多
Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study...Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.展开更多
AIM To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism. METHODS Eca 109 cells derived from human ESCC and Het-1A cells derived from human normal...AIM To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism. METHODS Eca 109 cells derived from human ESCC and Het-1A cells derived from human normal esophageal epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109 cells. The effect of miR-382 on cell proliferation was evaluated by MTT and colony formation assay. For cell cycle analysis, cells were fixed and stained for 30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100 mg/mL RNase A, and analyzed by BD FACSCalibur (TM) flow cytometer. For cell apoptosis assay, cells were stained with an Annexin V-FITC/PI Apoptosis Detection Kit according to the manufacturer's instructions and analyzed by a dual-laser flow cytometer. Cell invasion and migration abilities were determined through use of transwell chambers, non-coated or pre-coated with matrigel. Levels of proteins related to cell growth and migration were examined by western blotting. RESULTS Endogenous miR-382 was down-regulated in Eca109 cells compared with Het-1A. Introduction of miR-382 not only significantly inhibited proliferation and colony formation, but also arrested cell cycle at the G2/M phase, as well as promoted apoptosis and autophagy in Eca109 cells. Migration, invasion and epithelial-mesenchymal transition of Eca109 cells were suppressed by overexpressing miR-382. Western blotting results showed that miR-382 inhibited the phosphorylation of mTOR and 4E-BP1. CONCLUSION miR-382 functions as a tumor suppressor against ESCC development and metastasis, and could be considered as a potential drug source for the treatment of ESCC patients.展开更多
AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis(WGCNA) is applied to investigate the gene expression lev...AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis(WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study.METHODS: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus(GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes.The function of the genes were annotated by gene ontology(GO).RESULTS: In this study, we identified four co-expression modules significantly correlated with clinictraits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location(sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter(LTD). Additionally, we identified the hug gene(top connectivity with other genes) in each module. The hub gene RPS15 A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma.CONCLUSION: From WGCNA analysis and hub gene calculation, we identified RPS15 A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.展开更多
AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our ...AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043]. CONCLUSION: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.展开更多
Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of chan...Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.展开更多
WS2 exhibits tremendous potentials for Na-ions storage owing to high capacity(433 mAh g^(-1)). Nevertheless, WS2 layered structure is often exfoliated with rapid capacity decay and sluggish reaction kinetics.In this w...WS2 exhibits tremendous potentials for Na-ions storage owing to high capacity(433 mAh g^(-1)). Nevertheless, WS2 layered structure is often exfoliated with rapid capacity decay and sluggish reaction kinetics.In this work, WS2 nanosheets with different crystallinities are controlled by different synthesis methods.The high crystallinity WS2 exhibits high degree of interlayer order and strong interlayer force. It exhibits superior electrochemical properties, at the current density of 200 mA g^(-1) after 300 cycles with reversible capacity of 471 mAh g^(-1). Even at 5.0 A g^(-1), the capacities can still arrive at 240 mAh g^(-1) after 250 cycles, exhibiting stable cycling performance. Further electrochemical research finds that the high degree of interlayer order of layered WS2 structure can perform highly conducive Na+insertion/extraction with greatly improved contribution of intercalation capacity. Moreover, the strong interlayer force can effectively restrain the exfoliating of the WS2 nanosheets, guaranteeing the stability of the structure. Combining the above result reveals that controlling the order and force of the interlayer is an effective way to enhance the electrochemical properties of WS2 as SIBs anode materials. This work can provide new insight for inhibiting the exfoliation of layered compounds to pursue excellent electrochemical performance in Na-ion storage systems.展开更多
Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a co...Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.展开更多
Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eig...Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.展开更多
文摘The ultrasound pressure-strain loop (PSL) technique is a non-invasive method of examining myocardial work, which takes into account the effect of cardiac afterload on deformation and combines the overall longitudinal strain force of the left ventricle with the changes in the left ventricular pressure, allowing earlier detection of possible subclinical cardiac damage in patients, and a more accurate and non-invasive assessment of the patient’s myocardial work performance. In this article, we will discuss the progress of PSL applications in cardiovascular diseases.
基金Supported by The Science and Technology Department of Sichuan Province,No.2021JDKP0015.
文摘BACKGROUND The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis(HS)in children.We also hope to promote the application of gene detection technology in children with HS,with the goals of identifying more related gene mutations,supporting the acquisition of improved molecular genetic information to further reveal the pathogenesis of HS in children,and providing important guidance for the diagnosis,treatment,and prevention of HS in children.CASE SUMMARY A 1-year and 5-month-old patient presented jaundice during the neonatal period,mild anemia 8 months later,splenic enlargement at 1 year and 5 months,and brittle red blood cell permeability.Genetic testing was performed on the patient,their parents,and sister.Swiss Model software was used to predict the protein structure of complex heterozygous mutations in ANK1 and SPTA1.Genetic testing revealed that the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother.Combined with the clinical symptoms of the children,it is suggested that the newly discovered complex heterozygous mutations of ANK1 and SPTA1 may be the cause,providing important guidance for revealing the pathogenesis,diagnosis,treatment,and promotion of gene detection technology in children with HS.CONCLUSION This case involves an unreported complex heterozygous mutation of ANK1 and SPTA1,which provides a reference for exploring HS.
基金supported by the NSF of China(No.11671265)partially supported by NSF DMS-1848508+4 种基金partially supported by the NSF of China(under grant numbers 11688101,11571351,and 11731006)science challenge project(No.TZ2018001)the youth innovation promotion association(CAS)supported by the National Science Foundation under Grant No.DMS-1439786the Simons Foundation Grant No.50736。
文摘One of the open problems in the field of forward uncertainty quantification(UQ)is the ability to form accurate assessments of uncertainty having only incomplete information about the distribution of random inputs.Another challenge is to efficiently make use of limited training data for UQ predictions of complex engineering problems,particularly with high dimensional random parameters.We address these challenges by combining data-driven polynomial chaos expansions with a recently developed preconditioned sparse approximation approach for UQ problems.The first task in this two-step process is to employ the procedure developed in[1]to construct an"arbitrary"polynomial chaos expansion basis using a finite number of statistical moments of the random inputs.The second step is a novel procedure to effect sparse approximation via l1 minimization in order to quantify the forward uncertainty.To enhance the performance of the preconditioned l1 minimization problem,we sample from the so-called induced distribution,instead of using Monte Carlo(MC)sampling from the original,unknown probability measure.We demonstrate on test problems that induced sampling is a competitive and often better choice compared with sampling from asymptotically optimal measures(such as the equilibrium measure)when we have incomplete information about the distribution.We demonstrate the capacity of the proposed induced sampling algorithm via sparse representation with limited data on test functions,and on a Kirchoff plating bending problem with random Young’s modulus.
基金Supported by the National Natural Science Foundation of China (Nos.42130206,41302076)the MOST Special Fund awarded by the State Key Laboratory of Continental Dynamics,Northwest University (No.201210128)the Shandong Provincial Key Laboratory of Depositional Mineralization&Sedimentary Mineral,Shandong University of Science and Technology (No.DMSM2017033)。
文摘Six outcrop sections in Fenghe River,Northwestern China,were sampled and analyzed.This study aims to determine provenance,tectonic setting,and source-area paleoweathering of the sediments of Fenghe River in combination of lithofacies analysis and bulk-rock geochemical data.The lithofacies in the studied area were classified as gravel,sand,and fine-grained clastic lithofacies,reflecting generally channel fill deposits,channel bar deposits,and over-bank deposits,respectively.The Chemical Index of Alteration(CIA),Plagioclase Index of Alteration(PIA),and Chemical Index of Weathering(CIW)values ranged 50.10–62.29,50.13–66.35,56.52–71.12,respectively,together with element ratios such as Rb/Sr,K/Na,Rb/K,Th/K,Rb/Ti,and Cs/Ti indicate that the source area was under a low to moderate chemical weathering condition probably in cold and semi-arid climates.Moreover,plot of SiO_(2)vs.(Al_(2)O_(3)+K_(2)O+Na_(2)O)suggests that the sediments were deposited in a semi-arid climate.Plots of Cr/Th vs.Th/Sc,TiO_(2)vs.Zr,La/Yb vs.rare earth element(REE),and La-Th-Sc ternary diagrams,along with the lithology,indicate that the sediments in Fenghe River were mainly originated from felsic igneous rocks.Major elements-based discrimination diagrams and Th-Sc-Zr/10 and La-Th-Sc ternary diagram of the samples indicates that the source rocks of Fenghe River developed in a composite active continental margin and continental island arc field.
基金supported by the National Natural Science Foundation of China Grant 82273308,Inno HK@Health,Theme-based Research Scheme (Tl3-602/21-N)Guangdong-Dongguan Joint Research Scheme Guangdong-Hong Kong-Macao Program (2021B1515130004)+4 种基金the Natural Science Foundation of Guangdong Province Grant 2017B030301018the Special Support Program for Training High-Level Talents in Guangdong Grant 2019TQ05Y518the Shenzhen Innovation Committee of Science and Technology Grant JCYJ20220530112817040,ZDSYS20220606101604009the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen E010122002supported by the Lombardi and Shinozuka Experimental Pathology Research Endowment Fund,University of Pittsburgh。
文摘Endochondral ossification requires proper control of chondrocyte proliferation,differentiation,survival,and organization.Here we show that knockout ofα-parvin,an integrin-associated focal adhesion protein,from murine limbs causes defects in endochondral ossification and dwarfism.The mutant long bones were shorter but wider,and the growth plates became disorganized,especially in the proliferative zone.With two-photon time-lapse imaging of bone explant culture,we provide direct evidence showing thatα-parvin regulates chondrocyte rotation,a process essential for chondrocytes to form columnar structure.Furthermore,loss ofα-parvin increased binucleation,elevated cell death,and caused dilation of the resting zones of mature growth plates.Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones(i.e.,resting,proliferative,and hypertrophic zones)of the growth plates.Our results demonstrate a crucial role ofα-parvin in long bone development and shed light on the cellular mechanism through whichα-parvin regulates the longitudinal growth of long bones.
基金supported by grants from the National Natural Science Foundation of China (No. 81071890 and No. 81030043)Training Programme Foundation for the Talents by Sun Yat-sen University Cancer Center+3 种基金Program for New Century Excellent Talents in University in ChinaProgram for New Century Excellent Talents in University (NCET-12-0562)Sun Yat-sen University Clinical Research 5010 Program (201310)Guangdong Provincial Natural Science Foundation of China (S2013020012726)
文摘Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma(NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival(OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio(HR)=0.9, P=0.529]; this risk was 60% lower than that of the group undergoing supportive treatment(HR=0.4, P=0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy(HR=2.3, P<0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.
基金supported by a grant from the Principal Research Program of Clinical Disciplines of State Health Ministry(No.321)
文摘Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
基金Supported by Key Technologies R&D Program of Science and Technology Commission of Henan Province,No.152102310110 to Zhao BSKey Science and Technique Fund of Xinxiang,No.ZG15018 to Zhao BS
文摘AIM To explore the effect of miR-382 on esophageal squamous cell carcinoma (ESCC) in vitro and its possible molecular mechanism. METHODS Eca 109 cells derived from human ESCC and Het-1A cells derived from human normal esophageal epithelium were used. Lentivirus-mediated miR-382 was overexpressed in Eca109 cells. The effect of miR-382 on cell proliferation was evaluated by MTT and colony formation assay. For cell cycle analysis, cells were fixed and stained for 30 min with propidium iodide (PI) staining buffer containing 10 mg/mL PI and 100 mg/mL RNase A, and analyzed by BD FACSCalibur (TM) flow cytometer. For cell apoptosis assay, cells were stained with an Annexin V-FITC/PI Apoptosis Detection Kit according to the manufacturer's instructions and analyzed by a dual-laser flow cytometer. Cell invasion and migration abilities were determined through use of transwell chambers, non-coated or pre-coated with matrigel. Levels of proteins related to cell growth and migration were examined by western blotting. RESULTS Endogenous miR-382 was down-regulated in Eca109 cells compared with Het-1A. Introduction of miR-382 not only significantly inhibited proliferation and colony formation, but also arrested cell cycle at the G2/M phase, as well as promoted apoptosis and autophagy in Eca109 cells. Migration, invasion and epithelial-mesenchymal transition of Eca109 cells were suppressed by overexpressing miR-382. Western blotting results showed that miR-382 inhibited the phosphorylation of mTOR and 4E-BP1. CONCLUSION miR-382 functions as a tumor suppressor against ESCC development and metastasis, and could be considered as a potential drug source for the treatment of ESCC patients.
基金Supported by the National Natural Science Foundation of China(No.81271019No.61463046)Gansu Province Science Foundation for Youths(No.145RJYA282)
文摘AIM: To identify and understand the relationship between co-expression pattern and clinic traits in uveal melanoma, weighted gene co-expression network analysis(WGCNA) is applied to investigate the gene expression levels and patient clinic features. Uveal melanoma is the most common primary eye tumor in adults. Although many studies have identified some important genes and pathways that were relevant to progress of uveal melanoma, the relationship between co-expression and clinic traits in systems level of uveal melanoma is unclear yet. We employ WGCNA to investigate the relationship underlying molecular and phenotype in this study.METHODS: Gene expression profile of uveal melanoma and patient clinic traits were collected from the Gene Expression Omnibus(GEO) database. The gene co-expression is calculated by WGCNA that is the R package software. The package is used to analyze the correlation between pairs of expression levels of genes.The function of the genes were annotated by gene ontology(GO).RESULTS: In this study, we identified four co-expression modules significantly correlated with clinictraits. Module blue positively correlated with radiotherapy treatment. Module purple positively correlates with tumor location(sclera) and negatively correlates with patient age. Module red positively correlates with sclera and negatively correlates with thickness of tumor. Module black positively correlates with the largest tumor diameter(LTD). Additionally, we identified the hug gene(top connectivity with other genes) in each module. The hub gene RPS15 A, PTGDS, CD53 and MSI2 might play a vital role in progress of uveal melanoma.CONCLUSION: From WGCNA analysis and hub gene calculation, we identified RPS15 A, PTGDS, CD53 and MSI2 might be target or diagnosis for uveal melanoma.
基金Supported by The National 863 Program, Nos. SQ2009AA02-XK1482570 and 2006AA02A402Beijing Municipal Committee of Science and Technology, No. D0905001040631Beijing Capital Development Foundation of Health Bureau, No.2007-2051
文摘AIM: To investigate the expression of myofibrillogenesis regulator-1 (MR-1) in relation to clinicopathological parameters and postoperative survival in a group of Chinese patients with gastric cancer. METHODS: In our previous study of human wholegenome gene expression profiling, the differentially expressed genes were detected in the gastric cancer and its adjacent noncancerous mucosa. We found that MR-1 was associated with the location and differentiation of tumors. In this study, MR-1 protein expression was determined by immunohistochemistry in specimens of primary cancer and the adjacent noncancerous tissues from gastric cancer patients. A set of real-time quantitative polymerase chain reaction assays based on the Universal ProbeLibrary-a collection of 165 presynthesized, fluorescence-labeled locked nucleic acid hydrolysis probes-was designed specifically to detect the expression of MR-1 mRNA. The correlation was analyzed between the expression of MR-1 and other tumor characteristics which may influence the prognosis of gastric cancer patients. A retrospective cohort study on the prognosis was carried out and clinical data were collected from medical records. RESULTS: MR-1 mRNA and protein could be detected in gastric cancer tissues as well as in matched noncancerous tissues. MR-1 was up-regulated at both mRNA (5.459 ± 0.639 vs 1.233 ± 0.238, P < 0.001) and protein levels (34.2% vs 13.2%, P = 0.003) in gastric cancer tissues. Correlation analysis demonstrated that high expression of MR-1 in gastric cancer was significantly correlated with clinical stage (P = 0.034). Kaplan-Meier analysis showed that the postoperative survival of the MR-1 positive group tended to be poorer than that of the MR-1 negative group, and the difference was statistically significant (P = 0.002). Among all the patients with stageⅠ-Ⅳ carcinoma, the 5-year survival rates of MR-1 positive and negative groups were 50.40% and 12.70%, respectively, with respective median survival times of 64.27 mo (95%CI: 13.41-115.13) and 16.77 mo (95%CI: 8.80-24.74). Univariate and multivariate analyses were performed to compare the impact of MR-1 expression and other clinicopathological parameters on prognosis. In a univariate analysis on all 70 specimens, 6 factors were found to be significantly associated with the overall survival statistically: including MR-1 expression, depth of invasion, distant metastasis, lymph node metastasis, vascular invasion and the tumor node metastasis (TNM) stage based on the 7th edition of the International Union against Cancer TNM classification. To avoid the influence caused by univariate analysis, the expressions of MR-1 as well as other parameters were examined in multivariate Cox analysis. Clinicopathological variables that might affect the prognosis of gastric cancer patients were analyzed by Cox regression analysis, which showed that MR-1 expression and TNM stage were independent predictors of postoperative survival. The best mathematical multivariate Cox regression model consisted of two factors: MR-1 expression and TNM stage. Our results indicated that MR-1 protein could act as an independent marker for patient overall survival [Hazard ratio (HR): 2.215, P = 0.043]. CONCLUSION: MR-1 is an important variable that can be used to evaluate the outcome, prognosis and targeted therapy of gastric cancer patients.
基金This work was supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)the National Natural Science Foundation of China(Grant Nos.81425018,81672868,and 81802775)+10 种基金the Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)the Sun Yat-sen University Clinical Research 5010 Program,the Special Support Plan of Guangdong Province(Grant No.2014TX01R145)the Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)the Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)the Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)the Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)the Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)the Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)the National Science&Technology Pillar Program during the Twelfth Five-year Plan Period(Grant No.2014BAI09B10)the Natural Science Foundation of Guangdong Province(Grant No.2017A030312003Fundamental Research Funds for the Central Universities。
文摘Objective:Several studies have reported that the controlling nutritional status(CONUT)score is a prognostic predictor for survival among patients with different types of cancer.We assessed the prognostic value of changes in the CONUT score during treatment and theΔCONUT-EBV DNA score in patients with advanced nasopharyngeal carcinoma(NPC).Methods:We retrospectively analyzed 433 patients with advanced NPC having no evidence of metastasis from January 2007 to June 2011;the patients underwent radical concurrent chemoradiotherapy(CCRT)at Sun Yat-sen University Cancer Center and were grouped based on theirΔCONUT andΔCONUT-EBV DNA scores.Kaplan-Meier curves were used to compare the patient outcomes according to the cut-offΔCONUT score and theΔCONUT-EBV DNA scoring system.Results:Among all patients,overall survival(OS)was independently predicted by a highΔCONUT score(P=0.031)and high EBV DNA(P<0.001).TheΔCONUT-EBV DNA score[OS area under the curve(AUC)=0.621;progression free survival(PFS)-AUC=0.612;distant metastasis-free survival(DMFS)-AUC=0.622]was more predictive of OS,PFS,and DMFS in patients with advanced NPC than theΔCONUT score(OS-AUC=0.547;PFS-AUC=0.533;DMFS-AUC=0.522)and pretreatment plasma EBV DNA levels alone(OS-AUC=0.600;PFS-AUC=0.591,DMFS-AUC=0.610).TheΔCONUT-EBV DNA score was significantly correlated with OS,PFS,and DMFS in patients with advanced NPC treated with CCRT.Conclusions:TheΔCONUT-EBV DNA score may be useful in clinical practice as a convenient biomarker for predicting the outcomes in patients with advanced NPC treated with CCRT.
基金supported by the National Natural Science Foundation of China (Nos. 21701107, 51672165, and 51472152)the China Postdoctoral Science Foundation (No. 2016M592897XB)+3 种基金Technology and Natural Science Foundation of Shaanxi (No. 2018JQ5107)Key Program for International S&T Cooperation Projects of Shaanxi ProvinceXi’an Key Laboratory of green manufacture of ceramic materials Foundation No. 2019220214SYS017CG039China Graduate Innovation Fund of Shaanxi University of Science and Technology。
文摘WS2 exhibits tremendous potentials for Na-ions storage owing to high capacity(433 mAh g^(-1)). Nevertheless, WS2 layered structure is often exfoliated with rapid capacity decay and sluggish reaction kinetics.In this work, WS2 nanosheets with different crystallinities are controlled by different synthesis methods.The high crystallinity WS2 exhibits high degree of interlayer order and strong interlayer force. It exhibits superior electrochemical properties, at the current density of 200 mA g^(-1) after 300 cycles with reversible capacity of 471 mAh g^(-1). Even at 5.0 A g^(-1), the capacities can still arrive at 240 mAh g^(-1) after 250 cycles, exhibiting stable cycling performance. Further electrochemical research finds that the high degree of interlayer order of layered WS2 structure can perform highly conducive Na+insertion/extraction with greatly improved contribution of intercalation capacity. Moreover, the strong interlayer force can effectively restrain the exfoliating of the WS2 nanosheets, guaranteeing the stability of the structure. Combining the above result reveals that controlling the order and force of the interlayer is an effective way to enhance the electrochemical properties of WS2 as SIBs anode materials. This work can provide new insight for inhibiting the exfoliation of layered compounds to pursue excellent electrochemical performance in Na-ion storage systems.
基金supported by National Natural Science Foundation of China(Project No.81872805,82073771,82104085)Guangdong Basic and Applied Basic Research Foundation(Project No.2020A1515110147,2021A1515011418,2021A1515012025)。
文摘Acute liver failure(ALF)is a mortal and critical hepatic disease,in which oxidative stress,inflammation storm and hepatocyte death are crucial in the pathogenesis.Hence,in contrast to the control of a single link,a combination therapy targeting multiple pathogenic links of the disease will be a favorable means to control the progression of the disease.In this study,we constructed dimethyl itaconate-loaded liposomes modified with dodecyl gallate as a cocktail activator to investigate its functional role in acetaminophen(APAP)-induced ALF.Our results demonstrated that the cocktail activator acted on hepatocytes and triggered cocktail efficacy,thereby simultaneously attenuating APAP-induced hepatocyte damage and remodeling the damage microenvironment.The cocktail activator could effectively scavenge reactive oxygen species,inhibit excessive inflammatory responses and reduce cell death in impaired hepatocytes for detoxification.More importantly,the cocktail activator could remodel the damage microenvironment,thus further promoting hepatocyte expansion and specifically switching macrophages from the M1 to M2 phenotype for a favorable liver regeneration of ALF.Furthermore,in APAP-induced ALF mouse model,the cocktail activator improved liver function,alleviated histopathological damage and increased survival rate.In summary,these findings indicate that the cocktail activator may provide a promising therapeutic approach for ALF treatment as a nanomedicine.
基金supported by grants from the National Key R&D Program of China(Grant Nos.2017YFC1309003 and 2017YFC0908500)National Natural Science Foundation of China(Grant Nos.81425018,81672868,81802775,and 81602371)+10 种基金Sci-Tech Project Foundation of Guangzhou City(Grant No.201707020039)Sun Yat-sen University Clinical Research 5010 ProgramSpecial Support Plan of Guangdong Province(Grant No.2014TX01R145)Natural Science Foundation of Guangdong Province(Grant Nos.2017A030312003 and 2018A0303131004)Sci-Tech Project Foundation of Guangdong Province(Grant No.2014A020212103)Health&Medical Collaborative Innovation Project of Guangzhou City(Grant Nos.201400000001 and 201803040003)Planned Science and Technology Project of Guangdong Province(Grant No.2019B020230002)National Science&Technology Pillar Program during the Twelfth FiveYear Plan Period(Grant No.2014BAI09B10)Natural Science Foundation of Guangdong Province for Distinguished Young Scholar(Grant No.2018B030306001)Pearl River S&T Nova Program of Guangzhou(Grant No.201806010135)PhD Start-up Fund of Natural Science Foundation of Guangdong Province(Grant No.2016A030310221)。
文摘Objective:The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma(NPC).Methods:Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study.Clinicopathologic information for each patient was analyzed.Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model.Concordance index(C-index)and calibration curves were used to verify discrimination and calibration,respectively and the results validated using bootstrap resampling.Results:Microscopic positive lymph node>2[hazard ratio(HR),2.19;95%confidence interval(CI),1.30–3.68;P=0.003],extranodal extension(HR,2.75;95%CI,1.69–4.47;P<0.001),and lower neck involvement(HR,1.78;95%CI,1.04–3.04;P=0.034)were identified from multivariate analysis as independent factors for overall survival(OS).A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival(PFS).The novel scoring model demonstrated enhanced discrimination(C-index=0.69;95%CI,0.62–0.76)relative to the original recurrent tumor-node-metastasis(rTNM)staging system(C-index=0.56;95%CI,0.50–0.62),and was internally validated with a bootstrap-adjusted C-index of 0.70.The calibration curve showed good agreement between predicted probabilities and actual observations.Conclusions:The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.
