Multimodal sentiment analysis utilizes multimodal data such as text,facial expressions and voice to detect people’s attitudes.With the advent of distributed data collection and annotation,we can easily obtain and sha...Multimodal sentiment analysis utilizes multimodal data such as text,facial expressions and voice to detect people’s attitudes.With the advent of distributed data collection and annotation,we can easily obtain and share such multimodal data.However,due to professional discrepancies among annotators and lax quality control,noisy labels might be introduced.Recent research suggests that deep neural networks(DNNs)will overfit noisy labels,leading to the poor performance of the DNNs.To address this challenging problem,we present a Multimodal Robust Meta Learning framework(MRML)for multimodal sentiment analysis to resist noisy labels and correlate distinct modalities simultaneously.Specifically,we propose a two-layer fusion net to deeply fuse different modalities and improve the quality of the multimodal data features for label correction and network training.Besides,a multiple meta-learner(label corrector)strategy is proposed to enhance the label correction approach and prevent models from overfitting to noisy labels.We conducted experiments on three popular multimodal datasets to verify the superiority of ourmethod by comparing it with four baselines.展开更多
Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited pa...Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.展开更多
BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD...BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.展开更多
AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that...AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells. METHODS: We used ? ow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97 and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium (MTT) assay and investigated the expression of p53, bcl-2 and bax genes during denutrition, by RT-PCR and immuno? uorescence staining. RESULTS: The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively. SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells. CONCLUSION: It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the f ield of anticancer therapy.展开更多
AIM:To gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic values to predict tumor metastasis.METHODS:Human gastric cancer SGC-7901 cells were implanted into 24 severe...AIM:To gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic values to predict tumor metastasis.METHODS:Human gastric cancer SGC-7901 cells were implanted into 24 severe combined immune deficiency (SCID) mice,which were randomly divided into metastasis group (n=8),non-metastasis group (n=8),and normal group (n=8).Urinary metabolomic information was obtained by gas chromatography/mass spectrometry (GC/MS).RESULTS:There were significant metabolic differences among the three groups (t test,P < 0.05).Ten selected metabolites were different between normal and cancer groups (non-metastasis and metastasis groups),and seven metabolites were also different between non-metastasis and metastasis groups.Two diagnostic models for gastric cancer and metastasis were constructed respectively by the principal component analysis (PCA).These PCA models were confirmed by corresponding receiver operating characteristic analysis (area under the curve=1.00).CONCLUSION:The urinary metabolomic profile is different,and the selected metabolites might be instructive to clinical diagnosis or screening metastasis for gastric cancer.展开更多
BACKGROUND Chronic liver injury(CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin(DHM) resists oxidation and protects the liver. We ...BACKGROUND Chronic liver injury(CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin(DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosisrelated molecules. Therefore, we studied the influence of DHM on CLI and pyroptosis.AIM To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of DHM.METHODS Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride(CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-β-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related molecules.RESULTS Serum total cholesterol, low density lipoprotein, aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR-and pyrin domain-containing 3(NLRP3) and gasdermin D(GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these proteins in the DHM group was lower than that in the vehicle group. Quantitative reverse transcription PCR results showed that the expression of the pyroptosis-related genes caspase-1, NLRP3, GSDMD and interleukin-1β(IL-1β) in the CCl4 group was higher than that in the control group, while there was no significant change in NLRP3 and caspase-1 expression in the DHM group compared with that in the vehicle group, and the expression of GSDMD and IL-1β was decreased.CONCLUSION DHM improves CCl4-induced CLI and regulates the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic agent for CLI.展开更多
Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs mo...Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.展开更多
Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods: Standard microelectrode cell...Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe^(2+)(100 μmol/L, 200 μmol/L) on the left ventricular outflow tract autorhythmic cells.Heart tissues were perfused with FeSO_4(200 μmol/L) combing with CaCl_2(4.2 mmol/L), Verapamil,(1 μmol/L), and nickel chloride(200μmol/L) respectively to observe the influences of these contents on electrophysiology of FeSO_4(200μmol/L) on the left ventricular outflow tract autorhythmic cells.Results: Fe^(2+)at both 100 μmol/L and 200 μmol/L could change the electrophysiological parameters of the slow response autorhythmic cells of the left ventricular outflow tract in a concentrationdependent manner resulting into decrease in Vmax, APA and MDP, slower RPF and VDD, and prolonged APD_(50) and APD_(90)(P all <0.05).Besides, perfusion of increased Ca^(2+) concentration could partially offset the electrophysiological effects of Fe^(2+)(200 μmol/L).The L-type calcium channel(LTCC) blocker Verapamil(1 μmol/L) could block the electrophysiological effects of Fe^(2+)(200 μmol/L).But the T-type calcium channel(TTCC) blocker nickel chloride(NiCl_2, 200 μmol/L) could not block the electrophysiological effects of Fe^(2+)(200 μmol/L).Conclusions: Fe^(2+) can directly change the electrophysiological characteristics of the slow response autorhythmic cells of the left ventricular outflow tract probably through the L-type calcium channel.展开更多
BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical phy...BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl_4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm/s per V/m)(0.55 ±0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter(mL/min per100 g)(94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope(μm/s)(325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02)revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller(μm)(10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79).CONCLUSION The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.展开更多
Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during em...Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development.However,the involvement of pineal gland in the light transduction process remains to be elucidated.In the present study,we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.Results:A total of 600 eggs of White Leghorn(Shaver strain)were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light(12L:12D group)or 24 h of darkness(0L:24D group)for 18 d.Compared to 0L:24D group,the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability.The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1(IGF-1);primary secretion of the liver.Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area,wall thickness and lumen area on d 10 and d 12 post incubation.Rhythmic function analysis demonstrated that three clock related genes(brain and muscle ARNT-like-1,BMAL1;circadian locomotor output cycles kaput,CLOCK;and cryptochrome-1,CRY1)and a melatonin rate-limiting enzyme related gene(arylalkylamine N-acetyltransferase,AANAT)were rhythmically expressed in the pineal gland of the 12L:12D group,but not in the 0L:24D group.Simultaneously,the light stimulation also increased the concentration of melatonin(MT),which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.Conclusions:The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance.Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation.It may be the key organ in the photo-endocrine axis that regulates embryo development,and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1.展开更多
Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomark...Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.展开更多
Stone cells have been described to substantially influence pear fruit quality,as lignin and cellulose are the main components of stone cells.However,there are limited studies on the relationship between the variation ...Stone cells have been described to substantially influence pear fruit quality,as lignin and cellulose are the main components of stone cells.However,there are limited studies on the relationship between the variation and molecular basis of stone cells,lignin and cellulose content among different pear varieties.Here,to reveal the variation of stone cell content within different cultivated species,we collected 236 germplasms of sand pear(Pyrus pyrifolia)at 50 days after flower blooming(DAFB),the key stage of stone cell formation.In our results,we measured the content of stone cells,lignin and cellulose and found that these contents ranged from2.82%to 29.00%,8.84%to 55.30%and 11.52%to 30.55%,respectively.Further analysis showed that the variation coefficient of stone cell,lignin and cellulose content was 39.10%,28.03%and 16.71%,respectively.Additionally,a significant correlation between stone cell,lignin and cellulose content were detected,and the correlation coefficient between the contents of stone cell and lignin(0.912)was higher than between the contents of stone cell and cellulose(0.796).Moreover,the average lignin content(29.73%)was higher than the average cellulose content(18.03%)in stone cells in pear fruits,indicating that lignin is the main component of stone cell in pears.Finally,on the basic of the transcriptome data,we identified 10 transcription factors belonging to bHLH,ERF,MYB,and NAC transcript families,which might be involved in lignin formation in stone cells.qRT-PCR experiments verified coincident trends between expression of candidate genes and stone cell content.This research laid foundation for future studies on genetic variation of stone cells in pear fruits and provided important gene resources for stone cell regulation.展开更多
AIM:To report the changes in detection rate and characteristics of retinopathy of prematurity(ROP)in infants,during a 12-year period in Northwest China.METHODS:The medical records of infants were retrospectively colle...AIM:To report the changes in detection rate and characteristics of retinopathy of prematurity(ROP)in infants,during a 12-year period in Northwest China.METHODS:The medical records of infants were retrospectively collected and reviewed using an established clinical database.The detection rate and severity of ROP were compared between two consecutive periods(P1:2008-2013,P2:2014-2019).Gender,gestational age(GA),birth weight(BW),multiple births,delivery pattern,and postmenstrual age of the first fundus screen were analyzed in all visiting infants.RESULTS:During the 12-year study period,7832 infants were initially included;among them,1266(16.16%)were diagnosed with ROP,441 of whom(5.63%)developed severe ROP.Throughout the study period,the total number of infants being screened showed a trend of slight fluctuation after a rapid increase;however,an annual increase was observed in the number of infants diagnosed with ROP and severe ROP.The proportion of each stage at the first screening of infants with ROP was stable.The detection rate of ROP increased from 2.33%in 2008 to 16.18%in 2010,decreased to 10.73%in 2014,and then increased to 27.47%in 2019.For severe ROP,the detection rate gradually increased from 0 in 2008 to 12.49%in 2019.Among the infants with ROP,96(7.58%)did not meet the screening criteria set by the Chinese Medical Association in 2014(GA<32wk,or BW<2000 g);among them,14(1.11%)needed treatment because of severe ROP.CONCLUSION:From 2008 to 2019,the detection rates of ROP and severe ROP in infants screened in Northwest China were 16.16%and 5.63%,respectively.The characteristics of the ROP infants were similar to those in other middle-income regions.The"tertiary prevention network of ROP"is a potentially effective screening approach.展开更多
Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully det...Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population.Methods:We performed the first population study investigating the germline mutation status in more than 1,000(n=1,923)Chinese patients with CRC and examined their relationship with the somatic mutational landscape.Germline alterations were examined with a 58-gene next-generation sequencing panel,and somatic alterations were examined with a 605-gene panel.Results:A total of 92 pathogenic(P)mutations were identified in 85 patients,and 81 likely pathogenic(LP)germline mutations were identified in 62 patients,accounting for 7.6%(147/1,923)of all patients.MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups,respectively.Patients with P/LP mutations had a significantly higher ratio of microsatellite instability,highly deficient mismatch repair,family history of CRC,and lower age.The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group.The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the nonLynch syndrome group.Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Population risk analysis indicated that the overall odds ratio was 11.13(95%CI:8.289–15.44)for the P group and 20.68(95%CI:12.89–33.18)for the LP group.Conclusions:Distinct features were revealed in Chinese patients with CRC with germline mutations.The Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Patients with P/LP germline mutations exhibited higher CRC risk.展开更多
基金supported by STI 2030-Major Projects 2021ZD0200400National Natural Science Foundation of China(62276233 and 62072405)Key Research Project of Zhejiang Province(2023C01048).
文摘Multimodal sentiment analysis utilizes multimodal data such as text,facial expressions and voice to detect people’s attitudes.With the advent of distributed data collection and annotation,we can easily obtain and share such multimodal data.However,due to professional discrepancies among annotators and lax quality control,noisy labels might be introduced.Recent research suggests that deep neural networks(DNNs)will overfit noisy labels,leading to the poor performance of the DNNs.To address this challenging problem,we present a Multimodal Robust Meta Learning framework(MRML)for multimodal sentiment analysis to resist noisy labels and correlate distinct modalities simultaneously.Specifically,we propose a two-layer fusion net to deeply fuse different modalities and improve the quality of the multimodal data features for label correction and network training.Besides,a multiple meta-learner(label corrector)strategy is proposed to enhance the label correction approach and prevent models from overfitting to noisy labels.We conducted experiments on three popular multimodal datasets to verify the superiority of ourmethod by comparing it with four baselines.
基金funded by the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-003)National High Level Hospital Clinical Research Funding(2022-PUMCH-B-017)The Strategic Priority Research Program(Pilot study)"Biological Basis of Aging and Therapeutic Strategies"of the Chinese Academy of Sciences(grant XDB39040000).
文摘Objective To determine the diagnostic accuracy of the intensity of fasciculation evaluated by muscle ultrasound in the differential diagnosis of amyotrophic lateral sclerosis(ALS).Methods We prospectively recruited patients who had ALS and neuropathy-radiculopathy attending Peking Union Medical College Hospital from 2017 to 2020.Healthy adults from a community were recruited as healthy controls.Muscle strength was assessed using the Medical Research Council(MRC)scale.At the first visit to the hospital,patients were assessed for maximal grade of fasciculations,total fasciculation score,and fasciculation grade in 16 muscle groups of bilateral upper and lower limbs using ultrasonography.The sensitivity and specificity of maximal grade of fasciculations,total fasciculation score,and fasciculation grade for the diagnosis of ALS were assessed by receiver operating characteristic analyses.Results The percentage of limb muscles with a maximal fasciculation grade higher than grade 2 in ALS patients and neuropathy-radiculopathy patients was 84.9%and 9.8%,respectively(χ^(2)=172.436,P<0.01).Of the 16 limb muscles detected,the total fasciculation score[median(interquartile range)]was 29(15,41)in ALS patients and 3(0,8)in neuropathy-radiculopathy patients(Z=9.642,P<0.001).Remarkable fasciculations were seen in ALS patients whose muscles with a MRC score ranging from 2 to 4,followed by patients with MRC score 5,and then in those with MRC score 0 and 1.The sensitivity and specificity of total fasciculation score for diagnosis of ALS were 80.6%and 93.4%,respectively(cut-off value 14).In patients with ALS,for muscles with MRC score 4 and 5,the percentage of muscles with fasciculation grades≥3 was 42.3%and 24.1%respectively,while in neuropathy-radiculopathy patients,the percentage for muscles with MRC score 4 and 5 was only 1.7%and 0,respectively.Conclusion A combined analysis of fasciculation intensity and MRC score of the limb muscles may be helpful for differential diagnosis of ALS.
基金The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board(Approval No.2019082).
文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.
文摘AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells. METHODS: We used ? ow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97 and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium (MTT) assay and investigated the expression of p53, bcl-2 and bax genes during denutrition, by RT-PCR and immuno? uorescence staining. RESULTS: The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively. SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells. CONCLUSION: It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the f ield of anticancer therapy.
基金Supported by The Key Program of Science and Technology Commission of Shanghai Municipality,Project No.09JC1411600Natural Science Foundation of Shanghai,No.08ZR1411300
文摘AIM:To gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic values to predict tumor metastasis.METHODS:Human gastric cancer SGC-7901 cells were implanted into 24 severe combined immune deficiency (SCID) mice,which were randomly divided into metastasis group (n=8),non-metastasis group (n=8),and normal group (n=8).Urinary metabolomic information was obtained by gas chromatography/mass spectrometry (GC/MS).RESULTS:There were significant metabolic differences among the three groups (t test,P < 0.05).Ten selected metabolites were different between normal and cancer groups (non-metastasis and metastasis groups),and seven metabolites were also different between non-metastasis and metastasis groups.Two diagnostic models for gastric cancer and metastasis were constructed respectively by the principal component analysis (PCA).These PCA models were confirmed by corresponding receiver operating characteristic analysis (area under the curve=1.00).CONCLUSION:The urinary metabolomic profile is different,and the selected metabolites might be instructive to clinical diagnosis or screening metastasis for gastric cancer.
基金Supported by National Natural Science Foundation of China,No. 81873769Beijing Municipal Natural Science Foundation,No. 7162098。
文摘BACKGROUND Chronic liver injury(CLI) is now a worldwide disease. However, there is no effective treatment. Pyroptosis plays an essential role in CLI. Dihydromyricetin(DHM) resists oxidation and protects the liver. We hypothesize that the beneficial effect of DHM on CLI is related to its effect on the expression of pyroptosisrelated molecules. Therefore, we studied the influence of DHM on CLI and pyroptosis.AIM To study the role of pyroptosis in the pathogenesis of CLI and the therapeutic mechanism of DHM.METHODS Thirty-two mice were randomly divided into four groups: The control group was injected with olive oil, the carbon tetrachloride(CCl4) group was injected with CCl4, the vehicle group was injected with hydroxypropyl-β-cyclodextrin while injecting CCl4 and the DHM group was injected with DHM while injecting CCl4. After four weeks of treatment, liver tissues from the mice were stained with hematoxylin and eosin, and oil red O. Blood was collected from the angular vein for serological analysis. The severity of CLI was estimated. Some liver tissue was sampled for immunohistochemistry, Western blotting and quantitative reverse transcription PCR to observe the changes in pyroptosis-related molecules.RESULTS Serum total cholesterol, low density lipoprotein, aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the CCl4 group were higher than those in the control group, and serum total cholesterol, low density lipoprotein, AST and ALT in the DHM group were lower than those in the vehicle group. Hematoxylin and eosin and oil red O staining showed that there were more lipid droplets in the CCl4 group than in the control group, and there were fewer lipid droplets in the DHM group than in the vehicle group. Western blotting showed that the expression of the pyroptosis-related molecules caspase-1, NOD-, LRR-and pyrin domain-containing 3(NLRP3) and gasdermin D(GSDMD)-N in the CCl4 group was higher than that in the control group, while expression of these proteins in the DHM group was lower than that in the vehicle group. Quantitative reverse transcription PCR results showed that the expression of the pyroptosis-related genes caspase-1, NLRP3, GSDMD and interleukin-1β(IL-1β) in the CCl4 group was higher than that in the control group, while there was no significant change in NLRP3 and caspase-1 expression in the DHM group compared with that in the vehicle group, and the expression of GSDMD and IL-1β was decreased.CONCLUSION DHM improves CCl4-induced CLI and regulates the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic agent for CLI.
基金supported by Zhangjiakou Project of Science and Technology Studies and Development Planning(Grand No.1321078D)
文摘Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.Methods: Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet,pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency.Results: Compared with the control group, 4 phase automatic depolarization velocity,spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly(P < 0.01) and action potential amplitude reduced(P < 0.01) in model group. Moreover, repolarization 50% and 90% increased(P < 0.01).Conclusions: There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure.
基金supported by Zhangjiakou Project of Science and Technology Studies and Development Planning(Grand No.1321078D)
文摘Objective: To investigate the electrophysiology effects and mechanism of iron overload on the slow response autorhythmic cells in the left ventricular outflow tract of guinea pigs.Methods: Standard microelectrode cell recording techniques were adopted to observe the electrophysiological effects of different concentrations of Fe^(2+)(100 μmol/L, 200 μmol/L) on the left ventricular outflow tract autorhythmic cells.Heart tissues were perfused with FeSO_4(200 μmol/L) combing with CaCl_2(4.2 mmol/L), Verapamil,(1 μmol/L), and nickel chloride(200μmol/L) respectively to observe the influences of these contents on electrophysiology of FeSO_4(200μmol/L) on the left ventricular outflow tract autorhythmic cells.Results: Fe^(2+)at both 100 μmol/L and 200 μmol/L could change the electrophysiological parameters of the slow response autorhythmic cells of the left ventricular outflow tract in a concentrationdependent manner resulting into decrease in Vmax, APA and MDP, slower RPF and VDD, and prolonged APD_(50) and APD_(90)(P all <0.05).Besides, perfusion of increased Ca^(2+) concentration could partially offset the electrophysiological effects of Fe^(2+)(200 μmol/L).The L-type calcium channel(LTCC) blocker Verapamil(1 μmol/L) could block the electrophysiological effects of Fe^(2+)(200 μmol/L).But the T-type calcium channel(TTCC) blocker nickel chloride(NiCl_2, 200 μmol/L) could not block the electrophysiological effects of Fe^(2+)(200 μmol/L).Conclusions: Fe^(2+) can directly change the electrophysiological characteristics of the slow response autorhythmic cells of the left ventricular outflow tract probably through the L-type calcium channel.
基金Beijing Municipal Natural Science Foundation,No.7162098
文摘BACKGROUND Fatty liver(FL) is now a worldwide disease. For decades, researchers have been kept trying to elucidate the mechanism of FL at the molecular level, but rarely involve the study of morphology and medical physics. Traditionally, it was believed that hemodynamic changes occur only when fibrosis occurs, but it has been proved that these changes already show in steatosis stage, which may help to reveal the pathogenesis and its progress. Because the pseudolobules are not formed during the steatosis stage, this phenomenon may be caused by the compression of the liver microcirculation and changes in the hemodynamics.AIM To understand the pathogenesis of hepatic steatosis and to study the hemodynamic changes associated with hepatic steatosis.METHODS Eight-week-old male C57 BL/6 mice were divided into three groups randomly(control group, 2-wk group, and 4-wk group), with 16 mice per group. A hepatic steatosis model was established by subcutaneous injection of carbon tetrachloride in mice. After establishing the model, liver tissue from mice was stained with hematoxylin and eosin(HE), and oil red O stains. Blood was collected from the angular vein, and hemorheological parameters were estimated. A two-photon fluorescence microscope was used to examine the flow properties of red blood cells in the hepatic sinusoids.RESULTS Oil red O staining indicated lipid accumulation in the liver after CCl_4 treatment.HE staining indicated narrowing of the hepatic sinusoidal vessels. No significant difference was observed between the 2-wk and 4-wk groups of mice onmorphological examination. Hemorheological tests included whole blood viscosity(mPas, γ = 10 s-1/γ = 100 s-1)(8.83 ± 2.22/4.69 ± 1.16, 7.73 ± 2.46/4.22 ±1.32, and 8.06 ± 2.88/4.22 ± 1.50), red blood cell volume(%)(51.00 ± 4.00, 42.00 ±5.00, and 40.00 ± 3.00), the content of plasma fibrinase(g/L)(3.80 ± 0.50, 2.90 ±0.80, and 2.30 ± 0.70), erythrocyte deformation index(%)(44.49 ± 5.81, 48.00 ±15.29, and 44.36 ± 15.01), erythrocyte electrophoresis rate(mm/s per V/m)(0.55 ±0.11, 0.50 ± 0.11, and 0.60 ± 0.20), revealing pathological changes in plasma components and red blood cells of hepatic steatosis. Assessment of blood flow velocity in the hepatic sinusoids with a laser Doppler flowmeter(mL/min per100 g)(94.43 ± 14.64, 80.00 ± 12.12, and 67.26 ± 5.92) and two-photon laser scanning microscope(μm/s)(325.68 ± 112.66, 213.53 ± 65.33, and 173.26 ± 44.02)revealed that as the modeling time increased, the blood flow velocity in the hepatic sinusoids decreased gradually, and the diameter of the hepatic sinusoids became smaller(μm)(10.28 ± 1.40, 6.84 ± 0.93, and 5.82 ± 0.79).CONCLUSION The inner diameter of the hepatic sinusoids decreases along with the decrease in the blood flow velocity within the sinusoids and the changes in the systemic hemorheology.
基金Financial support of this study was provided by The National Key Research and Development Program of China(grant number 2016YFD0500502)China Agriculture Research Systems(grant number CARS-40)+1 种基金Fundamental Research Funds for Central Non-profit Scientific Institution(grant number 2018-YWF-YB-20)Agricultural Science and Technology Innovation Program(grant number ASTIP-IAS04).
文摘Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development.However,the involvement of pineal gland in the light transduction process remains to be elucidated.In the present study,we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.Results:A total of 600 eggs of White Leghorn(Shaver strain)were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light(12L:12D group)or 24 h of darkness(0L:24D group)for 18 d.Compared to 0L:24D group,the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability.The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1(IGF-1);primary secretion of the liver.Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area,wall thickness and lumen area on d 10 and d 12 post incubation.Rhythmic function analysis demonstrated that three clock related genes(brain and muscle ARNT-like-1,BMAL1;circadian locomotor output cycles kaput,CLOCK;and cryptochrome-1,CRY1)and a melatonin rate-limiting enzyme related gene(arylalkylamine N-acetyltransferase,AANAT)were rhythmically expressed in the pineal gland of the 12L:12D group,but not in the 0L:24D group.Simultaneously,the light stimulation also increased the concentration of melatonin(MT),which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.Conclusions:The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance.Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation.It may be the key organ in the photo-endocrine axis that regulates embryo development,and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1.
基金supported by grants from NIH(No.1R01LM010185,1U01CA166886,and 1U01HL111560)
文摘Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies-single nucleotide polymorphism (SNP) array and gene expression array-with gene motifs considered transcription factor -binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on coregulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
基金the National Key Research and Development Program(Grant No.2018YFD1000200)the Earmarked Fund for Jiangsu Agricultural Industry Technology System(Grant No.JATS[2019]420)the Earmarked Fund for China Agriculture Research System(Grant No.CARS-28).
文摘Stone cells have been described to substantially influence pear fruit quality,as lignin and cellulose are the main components of stone cells.However,there are limited studies on the relationship between the variation and molecular basis of stone cells,lignin and cellulose content among different pear varieties.Here,to reveal the variation of stone cell content within different cultivated species,we collected 236 germplasms of sand pear(Pyrus pyrifolia)at 50 days after flower blooming(DAFB),the key stage of stone cell formation.In our results,we measured the content of stone cells,lignin and cellulose and found that these contents ranged from2.82%to 29.00%,8.84%to 55.30%and 11.52%to 30.55%,respectively.Further analysis showed that the variation coefficient of stone cell,lignin and cellulose content was 39.10%,28.03%and 16.71%,respectively.Additionally,a significant correlation between stone cell,lignin and cellulose content were detected,and the correlation coefficient between the contents of stone cell and lignin(0.912)was higher than between the contents of stone cell and cellulose(0.796).Moreover,the average lignin content(29.73%)was higher than the average cellulose content(18.03%)in stone cells in pear fruits,indicating that lignin is the main component of stone cell in pears.Finally,on the basic of the transcriptome data,we identified 10 transcription factors belonging to bHLH,ERF,MYB,and NAC transcript families,which might be involved in lignin formation in stone cells.qRT-PCR experiments verified coincident trends between expression of candidate genes and stone cell content.This research laid foundation for future studies on genetic variation of stone cells in pear fruits and provided important gene resources for stone cell regulation.
基金Supported by the National Natural Science Foundation of China(No.81770936)Key Research and Development Program of Shaanxi Province(No.2021SF-159,No.2017SF-222,No.2015SF-217)。
文摘AIM:To report the changes in detection rate and characteristics of retinopathy of prematurity(ROP)in infants,during a 12-year period in Northwest China.METHODS:The medical records of infants were retrospectively collected and reviewed using an established clinical database.The detection rate and severity of ROP were compared between two consecutive periods(P1:2008-2013,P2:2014-2019).Gender,gestational age(GA),birth weight(BW),multiple births,delivery pattern,and postmenstrual age of the first fundus screen were analyzed in all visiting infants.RESULTS:During the 12-year study period,7832 infants were initially included;among them,1266(16.16%)were diagnosed with ROP,441 of whom(5.63%)developed severe ROP.Throughout the study period,the total number of infants being screened showed a trend of slight fluctuation after a rapid increase;however,an annual increase was observed in the number of infants diagnosed with ROP and severe ROP.The proportion of each stage at the first screening of infants with ROP was stable.The detection rate of ROP increased from 2.33%in 2008 to 16.18%in 2010,decreased to 10.73%in 2014,and then increased to 27.47%in 2019.For severe ROP,the detection rate gradually increased from 0 in 2008 to 12.49%in 2019.Among the infants with ROP,96(7.58%)did not meet the screening criteria set by the Chinese Medical Association in 2014(GA<32wk,or BW<2000 g);among them,14(1.11%)needed treatment because of severe ROP.CONCLUSION:From 2008 to 2019,the detection rates of ROP and severe ROP in infants screened in Northwest China were 16.16%and 5.63%,respectively.The characteristics of the ROP infants were similar to those in other middle-income regions.The"tertiary prevention network of ROP"is a potentially effective screening approach.
基金This study was supported by the Special Funds for Strategic Emerging Industry Development of Shenzhen(Grant No.20170922151538732)the Science and Technology Project of Shenzhen(Grant No.JSGG20180703164202084)+2 种基金the Natural Science Foundation Project of China(Grant No.71573022)the National Natural Science Foundation Regional Projects(Grant No.82060440)the special health research projects of 2019 funded by the Chinese PLA General Hospital(Grant No.NLBJ-2019003).
文摘Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population.Methods:We performed the first population study investigating the germline mutation status in more than 1,000(n=1,923)Chinese patients with CRC and examined their relationship with the somatic mutational landscape.Germline alterations were examined with a 58-gene next-generation sequencing panel,and somatic alterations were examined with a 605-gene panel.Results:A total of 92 pathogenic(P)mutations were identified in 85 patients,and 81 likely pathogenic(LP)germline mutations were identified in 62 patients,accounting for 7.6%(147/1,923)of all patients.MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups,respectively.Patients with P/LP mutations had a significantly higher ratio of microsatellite instability,highly deficient mismatch repair,family history of CRC,and lower age.The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group.The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the nonLynch syndrome group.Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Population risk analysis indicated that the overall odds ratio was 11.13(95%CI:8.289–15.44)for the P group and 20.68(95%CI:12.89–33.18)for the LP group.Conclusions:Distinct features were revealed in Chinese patients with CRC with germline mutations.The Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Patients with P/LP germline mutations exhibited higher CRC risk.
