ObjectiveTo analyze the epidemiological characteristics of 21 respiratory pathogens in influenza-like illness (ILI) cases in Jing’an District, Shanghai in 2024, and to provide a scientific basis for the prevention and control of respiratory infectious diseases. MethodsData of1 907 ILI cases at four sentinel hospitals in Jing’an District were collected from January to December 2024. Nasopharyngeal swab samples were collected and tested for 21 respiratory pathogens using polymerase chain reaction (PCR) methods. Chi-square test and Cochran-Armitage trend test were used for data analyses. ResultsAmong the 1 907 ILI cases, 1 340 were tested positive (70.27%), including 1 160 (60.83%) virus-positive cases, 424 (22.23%) bacteria-positive cases , and 86 (4.51%) positive cases of other pathogens (fungi, mycoplasma, and chlamydia). The top five viruses by detection rate were: influenza virus (14.84%), SARS-CoV-2 (14.47%), rhinovirus (12.69%), adenovirus (7.08%), and parainfluenza virus (6.71%). The top two bacteria by detection rate were Streptococcus pneumoniae (14.47%) and Haemophilus influenzae (10.33%). Among other pathogens (fungi, mycoplasma, and chlamydia), Mycoplasma pneumoniae showed the highest detection rate (4.30%). In terms of age distribution, statistically significant differences were observed in the detection rates of SARS-CoV-2, Legionella, and Klebsiella pneumoniae (P<0.05), with the highest rates found in individuals aged 65 years and above. Statistically significant differences were also found in the detection rates of rhinovirus, adenovirus, enterovirus, common coronavirus, respiratory syncytial virus, bocavirus, parainfluenza virus, human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae among different age groups (P<0.05), all showing the highest detection rates in the 0‒<15 years age group. In terms of seasonal distribution, SARS-CoV-2, adenovirus, parainfluenza virus, enterovirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae showed epidemic peaks in summer; rhinovirus, common coronavirus, bocavirus, and Klebsiella pneumoniae had higher detection rates in autumn. Influenza virus exhibited a peak incidence during winter, while human metapenu-movirus peaked in winter and spring. Significant differences in co-infection detection rates were observed among age groups, with the rate in children aged 0‒<15 years (34.81%) being the highest. The co-infection detection rate was higher in males than in females (P=0.019). Both the single-pathogen detection rate and the co-infection detection rate (P<0.001) varied significantly across seasons: the single-pathogen detection rate was highest in winter (62.06%), while the co-infection detection rate peaked in summer (31.20%) and was lowest in winter (14.52%). ConclusionBased on detection rates, the main pathogens in the ILI population of Jing’an District, Shanghai, 2024 were influenza virus, SARS-CoV-2, rhinovirus, adenovirus, parainfluenza virus, common coronavirus, enterovirus, Human metapenu-movirus, Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae. Pathogen detection rates varied by age and season. Coinfection rates were much higher in children than in adults, higher in males than in females, and peaked in summer while being lowest in winter.

Gestational trophoblastic neoplasia(GTN)patients can be classified into low-risk and high-risk patients based on the International Federation of Gynecology and Obstetrics(FIGO)staging and scoring system.High-risk patients have a higher risk of resistance to single-agent chemotherapy and require combination chemotherapy.Even worse,there are some high-risk patients who develop resistance to combination chemother-apy or experience recurrence after cure.These patients exhibit strong heterogeneity and pose significant challen-ges to subsequent treatment,thus attracting considerable attention in recent years.Therefore,this article aims to review the risk factors and treatment strategies for high-risk resistant and recurrent GTN patients,in order to provide a basis for early identification of high-risk patients and their precise treatment.

OBJECTIVE To understand the healthcare-seeking behavior of patients with AIDS co-infected with tu-berculosis and analyze the factors influencing delayed consultation and diagnosis,and to provide a theoretical basis for the implementation of interventional tuberculosis control measures.METHODS Two hundred and two patients with AIDS complicated with tuberculosis who were first admitted to Yunnan Infectious Diseases Hospital from Jan.2020 to Dec.2023 were selected,and their clinical data were collected through the inpatient medical record system.Multivariate logistic regression model was used to analyze the factors influencing delayed consultation and diagnosis.RESULTS Time of admission,place of residence,presence of lung cavities,distribution of lung lesions,intermediate hospital visited,sputum culture results,etiological situation,CD4+/CD8+cell ratio,and CD8+cell counts were the factors influencing delayed consultation(P<0.05).The initial diagnosis and Gene-Xpert results were the factors influencing delayed diagnosis(P<0.05).Multivariate logistic regression analysis showed that ad-mission in 2021(OR=3.842,95%CI:1.651-8.966),and presence of lung cavity(OR=8.007,95%CI:1.381-6.436),single lung lesion accumulation(OR=0.637,95%CI:0.049-8.267)were risk factors for delayed consultation.A 10%reduction in body mass(OR=2.070,95%CI:1.056-4.059)and negative Gene-Xpert re-sults(OR=1.667,95%CI:0.688-4.038)were risk factors for delayed diagnosis.CONCLUSIONS The issues of delayed medical consultation and diagnosis in patients with AIDS complicated with tuberculosis remain severe,with different factors influencing the delay.Special attention should be paid to the screening for latent tuberculosis infection in people infected with HIV.When experiencing suspicious symptoms,patients should go be encouraged to take exams at designated tuberculosis hospitals,repeatedly collect sputum samples and monitor changes in body mass,all of which are positively significant in reducing delays.

ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis （NASH） at the single-cell level using single-cell RNA sequencing （scRNA-seq）， and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient （MCD） diet， with three mice in each group， and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets， and related analyses were performed， including dimension clustering， cell type annotation， t-distributed stochastic neighbor embedding （t-SNE）， violin plot， gene ontology （GO） functional enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice， and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2， Cd8b1， Cd8a， and Tcf7. Tcf7， a characteristic marker gene for cluster 6， was expressed in 65% of cells in cluster 6， and therefore， cluster 6 was defined as Tcf7⁺ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation， leukocyte adhesion， binding ubiquitin-like protein ligase， and the signaling pathways for Th17， Th1， and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg， Tcrg-C1， Il2rα， and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7， and therefore， cluster 7 was defined as Cxcr6⁺ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation， cytokine production， the T cell receptor signaling pathway， and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group， the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein （1.80%±0.67% vs 0.33%±0.13%， P<0.05） and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein （0.50%±0.09% vs 2.66%± 0.33%， P<0.001）. ConclusionThere is a reduction in the percentage of Tcf7⁺ T cells and an increase in the percentage of Cxcr6⁺ T cells in NASH mice， revealing the characteristics and differences of T cells in the liver of NASH mice.

OBJECTIVE To understand the healthcare-seeking behavior of patients with AIDS co-infected with tu-berculosis and analyze the factors influencing delayed consultation and diagnosis,and to provide a theoretical basis for the implementation of interventional tuberculosis control measures.METHODS Two hundred and two patients with AIDS complicated with tuberculosis who were first admitted to Yunnan Infectious Diseases Hospital from Jan.2020 to Dec.2023 were selected,and their clinical data were collected through the inpatient medical record system.Multivariate logistic regression model was used to analyze the factors influencing delayed consultation and diagnosis.RESULTS Time of admission,place of residence,presence of lung cavities,distribution of lung lesions,intermediate hospital visited,sputum culture results,etiological situation,CD4+/CD8+cell ratio,and CD8+cell counts were the factors influencing delayed consultation(P<0.05).The initial diagnosis and Gene-Xpert results were the factors influencing delayed diagnosis(P<0.05).Multivariate logistic regression analysis showed that ad-mission in 2021(OR=3.842,95%CI:1.651-8.966),and presence of lung cavity(OR=8.007,95%CI:1.381-6.436),single lung lesion accumulation(OR=0.637,95%CI:0.049-8.267)were risk factors for delayed consultation.A 10%reduction in body mass(OR=2.070,95%CI:1.056-4.059)and negative Gene-Xpert re-sults(OR=1.667,95%CI:0.688-4.038)were risk factors for delayed diagnosis.CONCLUSIONS The issues of delayed medical consultation and diagnosis in patients with AIDS complicated with tuberculosis remain severe,with different factors influencing the delay.Special attention should be paid to the screening for latent tuberculosis infection in people infected with HIV.When experiencing suspicious symptoms,patients should go be encouraged to take exams at designated tuberculosis hospitals,repeatedly collect sputum samples and monitor changes in body mass,all of which are positively significant in reducing delays.

Gestational trophoblastic neoplasia (GTN) patients can be classified into low-risk and high-risk patients based on the International Federation of Gynecology and Obstetrics(FIGO) staging and scoring system. High-risk patients have a higher risk of resistance to single-agent chemotherapy and require combination chemotherapy. Even worse, there are some high-risk patients who develop resistance to combination chemotherapy or experience recurrence after cure. These patients exhibit strong heterogeneity and pose significant challenges to subsequent treatment, thus attracting considerable attention in recent years. Therefore, this article aims to review the risk factors and treatment strategies for high-risk resistant and recurrent GTN patients, in order to provide a basis for early identification of high-risk patients and their precise treatment.

Objective: The TCGA molecular subtype of endometrial cancer (EC) is widely applied, among which the copy-number high (CNH) subtype has the poorest prognosis. However, the heterogeneity of this subtype remains elusive. In this study, we aimed to identify heterogeneous immune subtypes in CNH EC and explore their prognostic significance. Methods: We collected 60 CNH EC cases in the TCGA database and performed unsupervised cluster analysis based on the enrichment scores of immune-related gene signatures to identify immune subtypes. We described their immune characteristics and prognoses and conducted differential gene analysis and lasso regression to identify a prognostic biomarker, GZMM. For experimental validation, we performed immunohistochemical staining of GZMM in 39 p53-positive EC surgical samples. Results: We defined two immune subtypes, immune-hot (IH) and immune-cold (IC), which differed in immune cell infiltration, cytokine and chemokine expression and prognosis. The IH subtype has significantly stronger immune activation than the IC subtype, showing a significant infiltration of immune effector cells and high expression of relevant chemokines, with better prognosis. Moreover, the immunohistochemical staining of GZMM in a cohort of 39 p53-positive EC surgical samples confirmed GZMM as a unique prognostic biomarker, with high expression in both tumor cells and lymphocytes predicting a better prognosis. Conclusion Our study revealed heterogeneous immune subtypes in CNH EC and identified GZMM as a prognostic biomarker. The stratified classification strategy combining molecular and immune subtypes provides valuable insights for future clinical practice.

Objective: The TCGA molecular subtype of endometrial cancer (EC) is widely applied, among which the copy-number high (CNH) subtype has the poorest prognosis. However, the heterogeneity of this subtype remains elusive. In this study, we aimed to identify heterogeneous immune subtypes in CNH EC and explore their prognostic significance. Methods: We collected 60 CNH EC cases in the TCGA database and performed unsupervised cluster analysis based on the enrichment scores of immune-related gene signatures to identify immune subtypes. We described their immune characteristics and prognoses and conducted differential gene analysis and lasso regression to identify a prognostic biomarker, GZMM. For experimental validation, we performed immunohistochemical staining of GZMM in 39 p53-positive EC surgical samples. Results: We defined two immune subtypes, immune-hot (IH) and immune-cold (IC), which differed in immune cell infiltration, cytokine and chemokine expression and prognosis. The IH subtype has significantly stronger immune activation than the IC subtype, showing a significant infiltration of immune effector cells and high expression of relevant chemokines, with better prognosis. Moreover, the immunohistochemical staining of GZMM in a cohort of 39 p53-positive EC surgical samples confirmed GZMM as a unique prognostic biomarker, with high expression in both tumor cells and lymphocytes predicting a better prognosis. Conclusion Our study revealed heterogeneous immune subtypes in CNH EC and identified GZMM as a prognostic biomarker. The stratified classification strategy combining molecular and immune subtypes provides valuable insights for future clinical practice.

Objective: The TCGA molecular subtype of endometrial cancer (EC) is widely applied, among which the copy-number high (CNH) subtype has the poorest prognosis. However, the heterogeneity of this subtype remains elusive. In this study, we aimed to identify heterogeneous immune subtypes in CNH EC and explore their prognostic significance. Methods: We collected 60 CNH EC cases in the TCGA database and performed unsupervised cluster analysis based on the enrichment scores of immune-related gene signatures to identify immune subtypes. We described their immune characteristics and prognoses and conducted differential gene analysis and lasso regression to identify a prognostic biomarker, GZMM. For experimental validation, we performed immunohistochemical staining of GZMM in 39 p53-positive EC surgical samples. Results: We defined two immune subtypes, immune-hot (IH) and immune-cold (IC), which differed in immune cell infiltration, cytokine and chemokine expression and prognosis. The IH subtype has significantly stronger immune activation than the IC subtype, showing a significant infiltration of immune effector cells and high expression of relevant chemokines, with better prognosis. Moreover, the immunohistochemical staining of GZMM in a cohort of 39 p53-positive EC surgical samples confirmed GZMM as a unique prognostic biomarker, with high expression in both tumor cells and lymphocytes predicting a better prognosis. Conclusion Our study revealed heterogeneous immune subtypes in CNH EC and identified GZMM as a prognostic biomarker. The stratified classification strategy combining molecular and immune subtypes provides valuable insights for future clinical practice.

BACKGROUND: Naloxone has a significant arousal effect on many types of comas. It is usually believed that this is because its inhibition on endogenous opioid peptides. But depth of coma is not necessarily positively correlated to endorphin (EP).OBJECTIVE: Based on existing findings on direct stimulating effect of naloxone on cerebral cortex, further studies need to be done to explore whether it is dose-dependent or not.DESIGN: Single-factor design based on cells.SETTING: Neurology department in a university hospital and the neurology department in a hospital of a military medical university of Chinese PLA.MATERIALS: This study was completed in the Laboratory Center of Tongji Medical College, Huazhong University of Science and Technology. Thirty healthy new born Wistar rats, regardless of their gender, aging 8 - 12 days and weighing 150 -250 g, were selected.METHODS: The experiment was performed at room temperature. The perfusion slot were placed on the microscope stage, and cells with smooth surfaces, triangle or pyramidal shapes, strong refraction and more than one neurites were selected for patch clamp experiment. Patch clamp whole-cell recording technique was used to measure the pyramidal cells of the frontal lobe immediately after separated from the Wistar rats, and to investigate the fluctuations of their membrane potential of cerebral cortex neurons and the frequencies of their spontaneous electric activities after administration of naloxone at different doses.MAIN OUTCOME MEASURES: The neural excitatory reaction rate, depolarization amplitude and increasing rate of spontaneous electric activities after administration of different doses of naloxone were selected as main outcome measurements.RESULTS: The excitatory reaction rates of cerebral cortex neurons immediately after separation to doses of naloxone(100, 50, 10, 1, 0. 1 μmol/L)were 83%, 67%, 86%, 71% and 33%; while the depolarization amplitude of them were 9. 8, 9.6, 8.4, 5.2 and 1. 3 mV respectively; and the corresponding spontaneous electric activity were increased by 587% , 375% ,291%, 125% and 69%.CONCLUSION: Naloxone can induce excitatory reactions in cerebral cortex neurons directly, and the reactions have proved to be dose-dependent.