ObjectiveTo analyze the epidemiological characteristics of foodborne disease outbreaks in Wuhan from 2006 to 2023, and to provide a scientific basis for the development of foodborne disease prevention and control measures. MethodsDescriptive statistical analyses were performed on foodborne disease outbreaks confirmed by the district and municipal center for disease control and prevention (CDC) in Wuhan from 2006 to 2023, and the attack rate and case fatality rate were calculated as well. ResultsA total of 182 foodborne disease outbreaks were reported in Wuhan from 2006 to 2023, with a cumulative of 2 820 cases. Among which, 3 cases were dead, with an annual average attack rate of 1.22% and a case fatality rate of 0.11%. The highest number of outbreaks occurred in collective canteens (43.96%, 80/182), the highest attack rate was observed in catering facilities (11.03%), and the highest case fatality rate was found in households (1.45%). Among the foodborne disease outbreaks with identified etiologies, microbial factors were the leading causes (36.26%, 66/182), with the main pathogens being norovirus, Bacillus cereus, and other unspecified bacteria. Fungal factors were mainly attributed to poisonous mushrooms, with a relatively high fatality rate of 2.22% (2/90). Outbreaks caused by bacterial factors were more common in the central urban area (30.28%, 33/109), while fungal-related outbreaks were more frequent in the outlying urban areas (24.66%, 18/73). ConclusionCollective canteens are the main venues for foodborne disease outbreaks in Wuhan. Microbial factors are the main pathogenic factors, and poisonous mushrooms are the leading causes to death. It is necessary to strengthen the supervision on collective canteens, carry out various forms of public awareness campaigns on poisonous mushroom poisoning, and, if required, cooperate with the gardening department to eradicate wild poisonous mushrooms in the green belts. A collaborative cooperation involving multiple departments is essential to reduce the occurrence of foodborne disease outbreaks.

Studies on specific transient receptor potential melastatin 2 (TRPM2) channel inhibitors can deepen our understanding of the pathological mechanism of related diseases, and allow discovery of novel, effective targets and drugs for therapy. The development of TRPM2 channel inhibitors can be broadly classified into four categories with distinct characteristics: reutilization and structural modification of homologous ion channel modulators to produce a diverse array of TRPM2 channel inhibitors with strong inhibitory effects; TRPM2 channel inhibitors based on channel gating mechanism with high specificity; inhibitors identified through high-throughput screening with novel chemical structures; inhibitors developed from natural antioxidants with higher safety. In recent years, the application of computer-aided drug design has significantly accelerated the development of TRPM2 channel inhibitors. Several promising compounds such as ZA18, A1 and D9 have been discovered, and it is expected that more potent and selective TRPM2 channel inhibitor scaffolds will be discovered in the future. This article reviews the advances on the studies of TRPM2 channel inhibitors, aiming to provide insights for further research and clinical application of TRPM2 channel inhibitors.
TRPM Cation Channels/antagonists & inhibitors* ; Humans ; Drug Design

Objective To investigate the expression level and diagnostic value of serum DNA polymerase α(DNA pol α)in Alzheimer's disease(AD),and analyze its diagnostic efficacy in AD.Methods A total of 100 patients of dementia of Alzheimer's type(DAT)and 43 patients of mild cognitive impairment(MCI)from Xuanwu Hospital Capital Medical University from March 2019 to April 2023 were included in this study,and 68 healthy individuals of the same age group were collected as the HC group.The expression level of DNA pol α was detected in each group,and the diagnostic value of DNA pol α in AD was analyzed by receiver oper-ating characteristic(ROC)curve.Results The expression level of DNA pol α in DAT group was higher than those in the MCI group(P＜0.05)and the HC group(P＜0.001).The expression level of DNA pol α showed an increasing trend as AD progressed.The expression level of DNA pol α was negatively correlated with Mini Intelligent Mental State Examination Scale(MMSE)score and Montreal Cognitive Assessment Scale(MoCA)score(r=-0.155 3,-0.203 7,P＜0.05).The area under the curve(AUC)of DNA pol α for diagnosing DAT was 0.682,and the sensitivity was 0.900.The AUC for diagnosing MCI was 0.546,and the sensitivity was 0.977.The AUC for differential diagnosis of MCI and DAT was 0.664,the sensitivity was 0.780,and the specificity was 0.535.Conclusion The expression level of DNA pol α is significantly increased in AD patients with DAT,and its expression level is related to the progression of AD,suggesting that DNA pol α has the pos-sibility to be a potential blood biomarker for the diagnosis of AD.

Objective To investigate the effects of zalcitabine(ddC),a mitochondrial DNA polymerase γ(POLG)inhibitor,on the migration,invasion,and to preliminarily explore mitochondrial biogenesis of human tri-ple-negative breast cancer MDA-MB-231 cells.Methods The effect of ddC on cell viability was detected using the MTT assay.The migration and invasion abilities of the cells were evaluated using the cell scratch and Transwell in-vasion assays.Cell apoptosis was determined using flow cytometry and a V-FITC/PI cell apoptosis detection kit.The protein expression of POLG,NADH dehydrogenase subunit Ⅰ(NADH1),NADH dehydrogenase subunit Ⅱ(NADH2),ATP synthase subunit 6(ATPase6),cytochrome c oxidase subunit Ⅰ(COX-1)and cytochrome c ox-idase subunit Ⅲ(COX-3)were determined using Western blot.The POLG mRNA level and mtDNA copy number were determined using qPCR.The mitochondrial content and ATP levels were determined using MitoTracker Green fluorescent probe staining and an ATP determination kit.MDA-MB-231 cells were transfected with pcDNA3.1-EG-FP-POLG plasmids to overexpress POLG.The inhibitory effects of ddC on cell migration and invasion were detected in POLG-overexpressed MDA-MB-231 cells.Results POLG expression was higher in MDA-MB-231 cells than in normal mammary epithelial cells(MCF-10A)(P＜0.01).ddC inhibited cell viability in a dose-dependent man-ner.ddC inhibited the migration(P＜0.01)and invasion(P＜0.01)of MDA-MB-231 cells;however,it dis-played no significant inhibitory effects on cell viability in normal mammary epithelial cells(MCF-10A)at the same concentration.ddC downregulated the protein(P＜0.01)and mRNA(P＜0.01)levels of POLG,reduced mtD-NA copy number(P＜0.01)and downregulated mtDNA-coded NADH1,NADH2,ATPase6,COX-1 and COX-3 protein expression(P＜0.01)in MDA-MB-231 cells.Furthermore ddC inhibited mitochondrial content(P＜0.01)and ATP(P＜0.01)levels in MDA-MB-231 cells.POLG overexpression increased the migration(P＜0.05)and invasion(P＜0.05)abilities of MDA-MB-231 cells,while ddC did not significantly inhibit the migra-tion and invasion abilities of MDA-MB-231 cells overexpressing POLG.Conclusion ddC downregulates POLG ex-pression in MDA-MB-231 cells and inhibits mitochondrial biogenesis and ATP levels,thereby inhibiting the migra-tion and invasion of MDA-MB-231 cells.

Objective To investigate the risk factors of stroke in nine hospitals of six cities of Shandong,and compare the differenc-es between residents of peninsula and inland areas. Methods Stroke patients in nine hospitals belonging to the Rehabilitation Medicine Alliance of Qilu Hospital of Shan-dong Universityfrom December,2022 to October,2023 were selected as the case group.The control group con-sisted of individuals undergoing health check-ups at the same hospitals during the same period.The sample size of both groups was equal,matched by age and gender,and demographic information and medical history were collected,and the risk factors of stroke were analyzed. Results A total of 438 cases were included.Residence in the inland(OR=2.07,95%CI 1.26 to 3.40,P=0.04),smoking(P=0.007),alcohol consumption(OR=6.67,95%CI 1.16 to 38.37,P=0.019),depression(OR=2.16,95%CI 1.03 to 4.53,P=0.042)and hypertension(OR=4.15,95%CI 2.34 to 7.39,P<0.001)were possible risk factors of stroke.However,smoking(OR=3.35,95%CI 1.11 to 10.10,P=0.013)and hypertension(OR=2.79,95%CI 1.12 to 6.95,P=0.004)were possible risk factors for the prevalence of stroke among residents in peninsula ar-eas,and obesity(excess waist circumference)(OR=1.08,95%CI 1.03 to 1.13,P=0.001),depression(OR=4.27,95%CI 1.38 to 13.23,P=0.013)and hypertension(OR=4.8,95%CI 2.21 to 10.43;P<0.001)were possi-ble risk factors for the prevalence of stroke among residents in the inland areas. Conclusion Hypertension is the most likely risk factor for stroke in nine hospitals of six cities of Shandong Province.Additionally,living inland,smoking and alcohol consumption may also increase the risk of stroke.There are dif-ferences in possible risk factors for stroke between peninsula and inland residents,and targeted stroke prevention and control measures should be implemented for different regions.

The occurrence of malignant tumors is closely related to the ministerial fire. The variant ministerial fire is the fundamental factor of the formation of cancer toxin， and ministerial fire dislocation and hyperactivity are the basis for the generation of variant ministerial fire. When the ministerial fire cannot keep its position or moves without restraint， burning and exuberant， the variant ministerial fire comes out. Under the guidance of the theory of ministerial fire， the basic treatment methods to differentiate and treat malignant tumors are the direct repulsion of variant ministerial fire， and the regulation of dislocated and hyperactive ministerial fire. The method of clearing heat and resolving toxins is often used， taking a large amounts of bitter and cold herbs to reduce variant ministerial fire. For ministerial fire dislocation， ministerial fire depletion， true yang insufficiency， and the ministerial fire failing to rely on， it is common to have symptoms of upper heat and lower cold， for which the treatment method is to benefit the source of the fire， and Modified Yinhuo Decoction （引火汤加减） is commonly used. For insufficient true yin and lack of support for ministerial fire， it is suggested to nourish kidney essence， and the medicinals of enriching yin and boosting kidney are commonly used. In terms of ministerial fire hyperactivity， the treatment method should be nourishing the heart and calming the mind， and Jiaotai Pills （交泰丸） is often used to clear heart and clam the mind， and return fire to its origin. At the same time， methods such as regulating qi， resolving phlegm， clearing fire， and dispelling stasis are used to clear away tangible pathogens， so that the ministerial fire acts in a controlled manner and keeps its position and destiny.

The incidence of lower extremity varicose veins is higher in the disease of venous system,and surgical treatment is the main treatment method of lower extremity varicose veins.With the advancement of technique and the development of minimally invasive concept,endovenous thermal ablation(EVTA)has become the first choice in the guidance of the treatment of lower extremity varicose veins depended on its series of advantages include small trauma,rapid recovery after surgery,low incidence of complication and high closure rate.At present,EVTA mainly includes intracavitary radiofrequency ablation(RFA),endovenous laser ablation(EVLA)and endovenous microwave ablation(EMA),which takes heat on target vessel through different thermal ablation equipment,and uses thermal energy to destruct the endothelial cells of blood vessel and collagen fibers in the vascular wall.Then,the contracted lumen forms the fibrous strands,thus reaches the aim that closes target vessel.Different EVTA surgical mode has different mechanism of action,therapeutic effect and incidence of complication,as well as the application range.This paper summarized the routinely surgical mode of EVTA and the clinical application of that in the past 5 years,which can provide references for reasonable choosing the mode of thermal ablation and the equipment,and can provide helps for preventing the complication of thermal injury.

Objective The aim of this study was to explore the correlation between the methylation status of microRNA let-7a-3 in esophageal squamous cell carcinoma(ESCC)and the expression of insulin-like growth factor 2(IGF-Ⅱ).Methods The methylation specific PCR(qMSP)was used to detect the methylation status of let-7a-3 in 83 cases of esophageal cancer and corre-sponding adjacent normal tissues.The enzyme linked immunosorbent assay(ELISA)was used to detect the expression of IGF-Ⅱ in plasma.Results The degree of let-7a-3 methylation in cancer tissues of 83 patients with ESCC was significantly higher than that in normal tissues adjacent to cancer(P<0.001).The expression of IGF-Ⅱ in the plasma of 83 patients with ESCC was positively corre-lated with the methylation degree of let-7a-3,which was statistically significant(r=0.600,P<0.001).Conclusion microRNAlet-7a-3 may participate in the occurrence and progression of ESCC by regulating the methylation of downstream molecules,which is of great significance for understanding the mechanisms of ESCC development and providing a basis for the diagnosis and prognosis of ESCC.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.