BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to hum...BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.展开更多
Objective It is difficult to predict fulminant myocarditis at an early stage in the emergency department.The objective of this study was to construct and validate a simple prediction model for the early identification...Objective It is difficult to predict fulminant myocarditis at an early stage in the emergency department.The objective of this study was to construct and validate a simple prediction model for the early identification of fulminant myocarditis.Methods A total of 61 patients with fulminant myocarditis and 160 patients with acute myocarditis were enrolled in the training and internal validation cohorts.LASSO regression and multivariate logistic regression were selected to develop the prediction model.The selection of the model was based on overall performance and simplicity.A nomogram based on the optimal model was built,and its clinical usefulness was evaluated by decision curve analysis.The predictive model was further validated in an external validation group.Results The resulting prediction model was based on 4 factors:systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality.The Brier scores of the final model were 0.078 in the training data set and 0.061 in the internal testing data set,respectively.The C-indexes of the training data set and the testing data set were 0.952 and 0.968,respectively.Decision curve analysis showed that the nomogram model developed based on the 4 predictors above had a positive net benefit for predicting probability thresholds.In the external validation cohort,the model also showed good performance(Brier score=0.007,and C-index=0.989).Conclusion We developed and validated an early prediction model consisting of 4 clinical factors(systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality)to identify potential fulminant myocarditis patients in the emergency department.展开更多
BACKGROUND In the information age,the use of the internet and multimedia tools has large effects on the life of middle school students.Improper use of the internet may result in internet addiction(IA).Thus,actively ex...BACKGROUND In the information age,the use of the internet and multimedia tools has large effects on the life of middle school students.Improper use of the internet may result in internet addiction(IA).Thus,actively exploring the factors influencing adolescent and the mechanism of addiction as well as promoting adolescent physical and mental health and academic development are priorities that families,schools,and society urgently need to address.AIM To explore the effect of childhood trauma on adolescent IA and to consider the roles of loneliness and negative coping styles.METHODS A total of 11310 students from six junior high schools in Henan,China,completed the child trauma questionnaire,IA test,loneliness scale,and simple coping style questionnaire.In addition,data were collected from 1044 adolescents with child-hood trauma for analysis with IBM SPSS 26.0 and AMOS 28.0;we examined the relationships among childhood trauma,IA,loneliness,and negative coping styles.RESULTS We found that childhood trauma not only directly affected adolescents’IA but also affected IA through loneliness and negative coping styles.CONCLUSION Therefore,this study has theoretical implications regarding adolescent mental health and may inform interventions for IA.展开更多
AIM:To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies.METHODS:Human gastric cance...AIM:To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies.METHODS:Human gastric cancer SGC-7901 and BGC823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors,and tumor tissue pieces were then implanted under the serous coat of the stomach.An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods.RESULTS:Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs.The gastric cavity became smaller,along with stenosis of the cardia or pylorus.There were biological and statistical differences between the two models.The metastasis rate in involved organs (lymph nodes,kidney,spleen,testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01).The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d,P < 0.05).Histopathologically,the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm.Compared with the SGC-7901 model,BGC-823 appeared more poorly differentiated (absence of adenoid structure),had a smaller volume,and richer capillary structure.Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors,while negative in BGC-823 ones.CONCLUSION:Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery.The two models showed different tumor behavior and the latter was more malignant than the former.展开更多
AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma(HCC) in Chinese patients with primary biliary cirrhosis(PBC).METHODS: We reviewed the data of 52 PB Cassociated HCC pat...AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma(HCC) in Chinese patients with primary biliary cirrhosis(PBC).METHODS: We reviewed the data of 52 PB Cassociated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13%(52/1255) and was significantly higher in the males(9.52%) than in the females(3.31%). Among the 52 PBC patients with HCC, 55.76%(29/52) were diagnosed with HCC and PBC simultaneously, and 5.76%(3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCCwere more likely than the females to have undergone blood transfusion(18.75% vs 8.33%, P = 0.043), consumed alcohol(31.25% vs 8.33%, P = 0.010), smoked(31.25% vs 8.33%, P = 0.010), had a family history of malignancy(25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase(P < 0.05). Conditional logistic regression analysis revealed that body mass index(BMI) ≥ 25 [adjusted odds ratio(AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake(AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
BACKGROUND Gastric stromal tumor is a digestive tract mesenchymal tumor with malignant potential, and endoscopic techniques have been widely used in the treatment of gastric stromal tumors, but there is still controve...BACKGROUND Gastric stromal tumor is a digestive tract mesenchymal tumor with malignant potential, and endoscopic techniques have been widely used in the treatment of gastric stromal tumors, but there is still controversy over their use for large gastric stromal tumors(≥ 3 cm).AIM To evaluate the clinical long-term efficacy and safety of endoscopic resection for large(≥ 3 cm) gastric stromal tumors.METHODS All patients who underwent endoscopic resection or surgery at our hospital from 2012 to 2017 for pathologically confirmed gastric stromal tumor with a maximum diameter of ≥ 3 cm were collected. The clinical data, histopathologic characteristics of the tumors, and long-term outcomes were recorded.RESULTS A total of 261 patients were included, including 37 patients in the endoscopy group and 224 patients in the surgical group. In the endoscopy group, the maximum tumor diameter was 3-8 cm; the male: Female ratio was 21/16; 34 cases had low-risk tumors, 3 had intermediate-risk, and 0 had high-risk; the mean follow-up time was 30.29 ± 19.67 mo, no patient was lost to follow-up, and no patient received chemotherapy after operation; two patients with recurrence had low-risk stromal tumors, and neither had complete resection under endoscopy. In the surgical group, the maximum tumor diameter was 3-22 cm; the male: Female ratio was 121/103; 103 cases had low-risk tumors, 75 had intermediate-risk, and 46 had high-risk; the average follow-up time was 38.83 ± 21.50 mo, 53 patients were lost to follow-up, and 8 patients had recurrence after operation(6 cases had high-risk tumors, 1 had intermediate-risk, and 1 had low-risk). The average tumor volume of the endoscopy group was 26.67 ± 26.22 cm^3(3.75-120), all of which were less than 125 cm^3. The average volume of the surgical group was 273.03 ± 609.74 cm^3(7-4114). Among all patients with a tumor volume < 125 cm^3,7 with high-risk stromal tumors in the surgical group(37.625 cm^3 to 115.2 cm^3)accounted for 3.8%(7/183); of those with a tumor volume < 125 cm^3, high-risk patients accounted for 50%(39/78). We found that 57.1%(12/22) of patients with high-risk stromal tumors also had endoscopic surface ulcer bleeding and tumor liquefaction on ultrasound or abdominal computed tomography; the ratio of tumors positive for both in high-risk stromal tumors with a volume < 125 cm^3 was 60%(3/5).CONCLUSION Endoscopic treatment is safe for 95.5% of patients with gastric stromal tumors with a tumor diameter ≥ 3 cm and a volume of < 125 cm^3 without endoscopic surface ulcer bleeding or CT liquefaction.展开更多
Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth.Streptococcus mutans(S. mutans) utilizes sortase A(Srt A) to anchor surface proteins to the ...Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth.Streptococcus mutans(S. mutans) utilizes sortase A(Srt A) to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of Srt A. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans Srt A. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity(ADMET)properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic parameters, were potential inhibitors to impede the catalysis of Srt A.In addition, the carbonyl of these compounds can have a key role in the inhibition mechanism. These findings can provide a new strategy for microbial infection disease therapy.展开更多
Objective Gestational diabetes mellitus(GDM)and gestational weight gain(GWG)are important risk factors that are known to affect offspring growth,but these outcomes are inconsistent and it remains unknown if both risk ...Objective Gestational diabetes mellitus(GDM)and gestational weight gain(GWG)are important risk factors that are known to affect offspring growth,but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth.The present study aimed to conduct offspring body mass index-for-age Z-scores(BMIZ)trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age.Methods A total of 7949 mother-child pairs were enrolled in this study.The weight and length of children were measured at birth,6,12,and 24 months of age to calculate BMIZ.Results The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6,12,and 24 months of age.In contrast,excessive GWG was positively linked to offspring BMIZ,the stable high BMIZ trajectory pattern,and risks of overweight/obesity in the first 24 months of age.These two risk factors also had a significant synergistic effect on macrosomia at birth,but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses.Conclusion The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood.The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.展开更多
Background: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus(HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of ...Background: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus(HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China.Methods: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P<0.05 was considered statistically significant.Results: Of the respondents, 665(91.5%) were male and 62(8.5%) were female. The mean age was 18.9±1.7 years. A total of 608 respondents(83.6%) demonstrated poor knowledge and 119(16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age(OR=3.040, 95%CI 1.724–5.359, P<0.001) and gender(OR=1.791, 95%CI 1.325–2.421, P<0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV.Conclusion: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.展开更多
OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin ...OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin penetrability of a topically applied hypericin,expecting reducing the risk of prolonged skin photosensitivity,which often occurs after systemic administration.METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers.In vivo studies,fluorescence microscopy was performed to examine the distribution of hypericin in the skin,macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment.Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin.RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most.The results of in vivo assays revealed that hypericin penetrated nude mice skin,spread to the dermis,and resulted in obvious photosensitivity reaction on the dermal capillaries.Moreover,skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treatment.CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.展开更多
Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in...Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.展开更多
Older individuals with macular diseases,such as age-related macular degeneration,experience central vision loss(CVL)due to degeneration of their photoreceptors and retinal cells.Patients with CVL may experience variou...Older individuals with macular diseases,such as age-related macular degeneration,experience central vision loss(CVL)due to degeneration of their photoreceptors and retinal cells.Patients with CVL may experience various vision impairments,including of visual acuity,fixation stability,contrast sensitivity,and stereoacuity.After CVL,most patients develop a preferred retinal locus outside the affected macular region,which serves as a new visual reference.In this review,we provide an overview of the visual function and impairment in individuals with CVL.In addition,the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed.Accordingly,the location and development of the preferred retinal loci are discussed.Finally,this review discusses how to conduct biofeedback training to treat individuals with CVL.展开更多
AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions w...AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors,and the tumor tissue pieces were implanted under the serous coat.The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases.RESULTS:Within 2-4 wk,there were no obvious chang-es about the primary tumor in stomach.At the sixth week,the primary tumor began to grow fast,resulting in incrassation of the gastric wall and stenosis of the gastric cavity,and metastases into the liver and lymph nodes were detected.The tumor,which compressed the adjacent organs,gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk.There were massive metastases,and the rate of metastasis was 58%in lymph nodes,78%in liver,39%in kidney,and 81%in peritoneum or septum.CONCLUSION:A gastric cancer model is established,which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.展开更多
Background:Hemorrhage is one of the most serious complications of endoscopic sphincterotomy(EST).The risk factors for delayed hemorrhage are not clear.This study aimed to explore the risk factors for post-EST delayed ...Background:Hemorrhage is one of the most serious complications of endoscopic sphincterotomy(EST).The risk factors for delayed hemorrhage are not clear.This study aimed to explore the risk factors for post-EST delayed hemorrhage and suggest some precautionary measures.Methods:This study analyzed 8477 patients who successfully underwent endoscopic retrograde cholangiopancreatography(ERCP)and EST between January 2007 and June 2015 in the First Affiliated Hospital of Nanchang University.Univariate and multivariate analyses were performed to find the risk factors for delayed hemorrhage after EST.Results:Of the 8477 patients screened,137(1.62%)experienced delayed hemorrhage.Univariate analysis showed that male,the severity of jaundice,duodenal papillary adenoma and carcinoma,diabetes,intraoperative bleeding,moderate and large incisions,and directional deviation of incision were risk factors for post-EST delayed hemorrhage(P<0.05).Multivariate analysis showed that intraoperative bleeding[odds ratio(OR)=3.326;95%CI:1.785–6.196;P<0.001]and directional deviation of incision(OR=2.184;95%CI:1.266–3.767;P=0.005)were independent risk factors for post-EST delayed hemorrhage.Conclusions:Delayed hemorrhage is the most common and dangerous complication of EST.Intraoperative bleeding and directional deviation of incision are independent risk factors for post-EST delayed hemorrhage.展开更多
文摘BACKGROUND The endoplasmic reticulum(ER)is closely related to a wide range of cellular functions and is a key component to maintain and restore metabolic health.Type 2 diabetes mellitus(T2DM)is a serious threat to human health,but the ER stress(ERS)-related mechanisms in T2DM have not been fully elucidated.AIM To identify potential ERS-related mechanisms and crucial biomarkers in T2DM.METHODS We conducted gene set enrichment analysis(GSEA)and gene set variation analysis(GSVA)in myoblast and myotube form GSE166502,and obtained the differentially expressed genes(DEGs).After intersecting with ERS-related genes,we obtained ERS-related DEGs.Finally,functional analyses,immune infiltration,and several networks were established.RESULTS Through GSEA and GSVA,we identified several metabolic and immune-related pathways.We obtained 227 ERS-related DEGs and constructed several important networks that help to understand the mechanisms and treatment of T2DM.Finally,memory CD4^(+)T cells accounted for the largest proportion of immune cells.CONCLUSION This study revealed ERS-related mechanisms in T2DM,which might contribute to new ideas and insights into the mechanisms and treatment of T2DM.
文摘Objective It is difficult to predict fulminant myocarditis at an early stage in the emergency department.The objective of this study was to construct and validate a simple prediction model for the early identification of fulminant myocarditis.Methods A total of 61 patients with fulminant myocarditis and 160 patients with acute myocarditis were enrolled in the training and internal validation cohorts.LASSO regression and multivariate logistic regression were selected to develop the prediction model.The selection of the model was based on overall performance and simplicity.A nomogram based on the optimal model was built,and its clinical usefulness was evaluated by decision curve analysis.The predictive model was further validated in an external validation group.Results The resulting prediction model was based on 4 factors:systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality.The Brier scores of the final model were 0.078 in the training data set and 0.061 in the internal testing data set,respectively.The C-indexes of the training data set and the testing data set were 0.952 and 0.968,respectively.Decision curve analysis showed that the nomogram model developed based on the 4 predictors above had a positive net benefit for predicting probability thresholds.In the external validation cohort,the model also showed good performance(Brier score=0.007,and C-index=0.989).Conclusion We developed and validated an early prediction model consisting of 4 clinical factors(systolic blood pressure,troponin I,left ventricular ejection fraction,and ventricular wall motion abnormality)to identify potential fulminant myocarditis patients in the emergency department.
基金This study was approved by the Institutional Review Committee of Henan Provincial Key Laboratory of Psychology and Behavior(20230516001).
文摘BACKGROUND In the information age,the use of the internet and multimedia tools has large effects on the life of middle school students.Improper use of the internet may result in internet addiction(IA).Thus,actively exploring the factors influencing adolescent and the mechanism of addiction as well as promoting adolescent physical and mental health and academic development are priorities that families,schools,and society urgently need to address.AIM To explore the effect of childhood trauma on adolescent IA and to consider the roles of loneliness and negative coping styles.METHODS A total of 11310 students from six junior high schools in Henan,China,completed the child trauma questionnaire,IA test,loneliness scale,and simple coping style questionnaire.In addition,data were collected from 1044 adolescents with child-hood trauma for analysis with IBM SPSS 26.0 and AMOS 28.0;we examined the relationships among childhood trauma,IA,loneliness,and negative coping styles.RESULTS We found that childhood trauma not only directly affected adolescents’IA but also affected IA through loneliness and negative coping styles.CONCLUSION Therefore,this study has theoretical implications regarding adolescent mental health and may inform interventions for IA.
基金Supported by A grant from the Natural Science Foundation of China,No.30830040
文摘AIM:To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies.METHODS:Human gastric cancer SGC-7901 and BGC823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors,and tumor tissue pieces were then implanted under the serous coat of the stomach.An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods.RESULTS:Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs.The gastric cavity became smaller,along with stenosis of the cardia or pylorus.There were biological and statistical differences between the two models.The metastasis rate in involved organs (lymph nodes,kidney,spleen,testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01).The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d,P < 0.05).Histopathologically,the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm.Compared with the SGC-7901 model,BGC-823 appeared more poorly differentiated (absence of adenoid structure),had a smaller volume,and richer capillary structure.Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors,while negative in BGC-823 ones.CONCLUSION:Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery.The two models showed different tumor behavior and the latter was more malignant than the former.
基金Supported by National Natural Science Foundation of China,No.81470837,No.81101589 and No.81302593
文摘AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma(HCC) in Chinese patients with primary biliary cirrhosis(PBC).METHODS: We reviewed the data of 52 PB Cassociated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant. RESULTS: The incidence of HCC in Chinese PBC patients was 4.13%(52/1255) and was significantly higher in the males(9.52%) than in the females(3.31%). Among the 52 PBC patients with HCC, 55.76%(29/52) were diagnosed with HCC and PBC simultaneously, and 5.76%(3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCCwere more likely than the females to have undergone blood transfusion(18.75% vs 8.33%, P = 0.043), consumed alcohol(31.25% vs 8.33%, P = 0.010), smoked(31.25% vs 8.33%, P = 0.010), had a family history of malignancy(25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase(P < 0.05). Conditional logistic regression analysis revealed that body mass index(BMI) ≥ 25 [adjusted odds ratio(AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake(AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients. CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
文摘BACKGROUND Gastric stromal tumor is a digestive tract mesenchymal tumor with malignant potential, and endoscopic techniques have been widely used in the treatment of gastric stromal tumors, but there is still controversy over their use for large gastric stromal tumors(≥ 3 cm).AIM To evaluate the clinical long-term efficacy and safety of endoscopic resection for large(≥ 3 cm) gastric stromal tumors.METHODS All patients who underwent endoscopic resection or surgery at our hospital from 2012 to 2017 for pathologically confirmed gastric stromal tumor with a maximum diameter of ≥ 3 cm were collected. The clinical data, histopathologic characteristics of the tumors, and long-term outcomes were recorded.RESULTS A total of 261 patients were included, including 37 patients in the endoscopy group and 224 patients in the surgical group. In the endoscopy group, the maximum tumor diameter was 3-8 cm; the male: Female ratio was 21/16; 34 cases had low-risk tumors, 3 had intermediate-risk, and 0 had high-risk; the mean follow-up time was 30.29 ± 19.67 mo, no patient was lost to follow-up, and no patient received chemotherapy after operation; two patients with recurrence had low-risk stromal tumors, and neither had complete resection under endoscopy. In the surgical group, the maximum tumor diameter was 3-22 cm; the male: Female ratio was 121/103; 103 cases had low-risk tumors, 75 had intermediate-risk, and 46 had high-risk; the average follow-up time was 38.83 ± 21.50 mo, 53 patients were lost to follow-up, and 8 patients had recurrence after operation(6 cases had high-risk tumors, 1 had intermediate-risk, and 1 had low-risk). The average tumor volume of the endoscopy group was 26.67 ± 26.22 cm^3(3.75-120), all of which were less than 125 cm^3. The average volume of the surgical group was 273.03 ± 609.74 cm^3(7-4114). Among all patients with a tumor volume < 125 cm^3,7 with high-risk stromal tumors in the surgical group(37.625 cm^3 to 115.2 cm^3)accounted for 3.8%(7/183); of those with a tumor volume < 125 cm^3, high-risk patients accounted for 50%(39/78). We found that 57.1%(12/22) of patients with high-risk stromal tumors also had endoscopic surface ulcer bleeding and tumor liquefaction on ultrasound or abdominal computed tomography; the ratio of tumors positive for both in high-risk stromal tumors with a volume < 125 cm^3 was 60%(3/5).CONCLUSION Endoscopic treatment is safe for 95.5% of patients with gastric stromal tumors with a tumor diameter ≥ 3 cm and a volume of < 125 cm^3 without endoscopic surface ulcer bleeding or CT liquefaction.
基金supported in part by the National Natural Science Foundation of China (Nos 31300674,81173093,30970643,81373311 and J1103518)the Special Programme for Youth Science and the Technology Innovative Research Group of Sichuan Province,China (No 2011JTD0026)
文摘Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth.Streptococcus mutans(S. mutans) utilizes sortase A(Srt A) to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of Srt A. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans Srt A. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity(ADMET)properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic parameters, were potential inhibitors to impede the catalysis of Srt A.In addition, the carbonyl of these compounds can have a key role in the inhibition mechanism. These findings can provide a new strategy for microbial infection disease therapy.
基金Fundamental Research Funds for the Central Universities(No.2015ZDTD047,No.2016YXZD043 and No.2018KFYXMPT00)Program for HUST Academic Frontier Youth Team(No.2018QYTD12)Grants from the National Key Research and Development Plan(No.2016YFC0206203).
文摘Objective Gestational diabetes mellitus(GDM)and gestational weight gain(GWG)are important risk factors that are known to affect offspring growth,but these outcomes are inconsistent and it remains unknown if both risk factors have a synergetic effect on early childhood growth.The present study aimed to conduct offspring body mass index-for-age Z-scores(BMIZ)trajectories and to evaluate the independent and interactive effect of the status of GDM and excessive GWG on the risks of overweight/obesity from birth to 24 months of age.Methods A total of 7949 mother-child pairs were enrolled in this study.The weight and length of children were measured at birth,6,12,and 24 months of age to calculate BMIZ.Results The status of GDM was positively associated with offspring BMIZ and risk of macrosomia at birth but was not associated with offspring BMIZ or the risks of overweight/obesity at 6,12,and 24 months of age.In contrast,excessive GWG was positively linked to offspring BMIZ,the stable high BMIZ trajectory pattern,and risks of overweight/obesity in the first 24 months of age.These two risk factors also had a significant synergistic effect on macrosomia at birth,but the interactive effect was only significant in boys during the follow-up years in the sex-stratified analyses.Conclusion The maternal GWG was a more pronounced predictor than GDM with relation to BMIZ and risk of overweight/obesity in early childhood.The interactive effect between these risk factors on offspring overweight/obesity may vary by sex.
基金funded by the Key Technology Research of Prevention and Controlling Infectious Diseases Fund(BWS11J048)the National Military Construction Project
文摘Background: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus(HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China.Methods: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P<0.05 was considered statistically significant.Results: Of the respondents, 665(91.5%) were male and 62(8.5%) were female. The mean age was 18.9±1.7 years. A total of 608 respondents(83.6%) demonstrated poor knowledge and 119(16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age(OR=3.040, 95%CI 1.724–5.359, P<0.001) and gender(OR=1.791, 95%CI 1.325–2.421, P<0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV.Conclusion: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.
文摘OBJECTIVE Hypericin,a powerful naturally photosensitizer in photodynamic therapy(PDT),is suitable for treating skin diseases involving excess capillary proliferation.In the present study,we aimed to evaluate the skin penetrability of a topically applied hypericin,expecting reducing the risk of prolonged skin photosensitivity,which often occurs after systemic administration.METHODS The Franz diffusion cell assay was performed to evaluate different penetration enhancers.In vivo studies,fluorescence microscopy was performed to examine the distribution of hypericin in the skin,macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment.Immunohistochemistry was used to determine the expression of PECAM-1 in the treated skin.RESULTS 5% menthol facilitated hypericin penetrate the skin of nude mice most.The results of in vivo assays revealed that hypericin penetrated nude mice skin,spread to the dermis,and resulted in obvious photosensitivity reaction on the dermal capillaries.Moreover,skin injured by the photosensitive reaction induced by hypericin was replaced by normal skin 7 d after hypericin-PDT treatment.CONCLUSION Topical hypericin could penetrate nude mouse skin well and be great potential in PDT treatment of skin diseases.
基金This work was supported by the National Key Research&Development Program of China(No.2021YFC2701402).
文摘Objective This study aimed to explore the value of M701,targeting epithelial cell adhesion molecule(EpCAM)and CD3,in the immunotherapy of ovarian cancer ascites by the in vitro assay.Methods The expression of EpCAM in ovarian cancer tissues was analyzed by databases.The EpCAM expression and immune cell infiltration in different foci of ovarian cancer were detected by 8-channel flow cytometry.The toxic effect of M701 on OVCAR3 was tested using the in vitro cytotoxicity assay.The 3D cell culture and drug intervention experiments were performed to evaluate the therapeutic effect of M701 in ovarian cancer specimens.Flow cytometry was used to examine the effect of M701 on the binding of immune cells to tumor cells and the activation capacity of T cells.Results The results of the bioinformatic analysis showed that the expression of EpCAM in ovarian cancer tissue was significantly higher than that in normal ovarian tissue.The 8-channel flow cytometry of clinical samples showed that the EpCAM expression and lymphocyte infiltration were significantly heterogeneous among ovarian cancer patients and lesions at different sites.The in vitro experiment results showed that M701 had a significant killing effect on OVCAR3 cells.M701 also obviously killed primary tumor cells derived from some patients with ovarian cancer ascites.M701 could mediate the binding of CD3^(+)T cells to EpCAM^(+)tumor cells and induce T cell activation in a dose-dependent manner.Conclusion M701 showed significant inhibitory activity on tumor cells derived from ovarian cancer ascites,which had a promising application in immunotherapy for patients with ovarian cancer ascites.
基金Supported by the National Natural Science Foundation of China(No.81874494)Natural Science Foundation of Beijing Municipality(No.7182187)+1 种基金Capital Foundation of Medical Development(No.2020-2-4182No.2020-3-4184)。
文摘Older individuals with macular diseases,such as age-related macular degeneration,experience central vision loss(CVL)due to degeneration of their photoreceptors and retinal cells.Patients with CVL may experience various vision impairments,including of visual acuity,fixation stability,contrast sensitivity,and stereoacuity.After CVL,most patients develop a preferred retinal locus outside the affected macular region,which serves as a new visual reference.In this review,we provide an overview of the visual function and impairment in individuals with CVL.In addition,the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed.Accordingly,the location and development of the preferred retinal loci are discussed.Finally,this review discusses how to conduct biofeedback training to treat individuals with CVL.
基金Supported by the Natural Science Foundation of China,No. 30830040
文摘AIM:To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points.METHODS:Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors,and the tumor tissue pieces were implanted under the serous coat.The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases.RESULTS:Within 2-4 wk,there were no obvious chang-es about the primary tumor in stomach.At the sixth week,the primary tumor began to grow fast,resulting in incrassation of the gastric wall and stenosis of the gastric cavity,and metastases into the liver and lymph nodes were detected.The tumor,which compressed the adjacent organs,gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk.There were massive metastases,and the rate of metastasis was 58%in lymph nodes,78%in liver,39%in kidney,and 81%in peritoneum or septum.CONCLUSION:A gastric cancer model is established,which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.
文摘Background:Hemorrhage is one of the most serious complications of endoscopic sphincterotomy(EST).The risk factors for delayed hemorrhage are not clear.This study aimed to explore the risk factors for post-EST delayed hemorrhage and suggest some precautionary measures.Methods:This study analyzed 8477 patients who successfully underwent endoscopic retrograde cholangiopancreatography(ERCP)and EST between January 2007 and June 2015 in the First Affiliated Hospital of Nanchang University.Univariate and multivariate analyses were performed to find the risk factors for delayed hemorrhage after EST.Results:Of the 8477 patients screened,137(1.62%)experienced delayed hemorrhage.Univariate analysis showed that male,the severity of jaundice,duodenal papillary adenoma and carcinoma,diabetes,intraoperative bleeding,moderate and large incisions,and directional deviation of incision were risk factors for post-EST delayed hemorrhage(P<0.05).Multivariate analysis showed that intraoperative bleeding[odds ratio(OR)=3.326;95%CI:1.785–6.196;P<0.001]and directional deviation of incision(OR=2.184;95%CI:1.266–3.767;P=0.005)were independent risk factors for post-EST delayed hemorrhage.Conclusions:Delayed hemorrhage is the most common and dangerous complication of EST.Intraoperative bleeding and directional deviation of incision are independent risk factors for post-EST delayed hemorrhage.
