Objective: To discuss the epidemiological characteristics of hand foot mouth disease (HFMD) among children in Jiujiang City, and its correlation with meteorological factors, so as to provide scientific evidence for developing targeted HFMD prevention and control measures. Methods: HFMD incidence data among children and meteorological factor records from Jiujiang City during 2019-2023 were collected. Pearson correlation analysis and Quasi-Poisson regression analysis of generalized additive model were used to analyze the relationship between the number of cases and meteorological factors, calculating correlation coefficients (r) and excess risk (ER). Results: The annual reported children HFMD cases in Jiujiang City during 2019-2023 were 4 299, 4 671, 2 560, 3 230, and 3 584, respectively. Except for a peak in autumn-winter in 2020, outbreaks occurred mainly in spring and summer in other years. The majority of cases involved scattered children (71.11%) and children in daycare centers (26.64%). Pearson correlation analysis showed that total case counts, cases among scattered children, and cases among children in daycare centers were positively correlated with average temperature ( r =0.36, 0.39, 0.23), maximum temperature ( r =0.32, 0.36, 0.20), minimum temperature ( r =0.37, 0.41, 0.24), and average relative humidity ( r =0.19, 0.20, 0.15) (all P <0.05). Quasi-Poisson regression analysis of generalized additive model revealed that total cases, cases among scattered children, and cases among daycare children were positively associated with average temperature ( r =0.05, 0.06, 0.03) and average relative humidity ( r =0.03, 0.02, 0.02) (all P <0.01). Excess incidence risk analysis indicated that for every 10 ℃ increase in average temperature, the ER (95% CI ) values were 72.16 (45.91-103.14), 79.76 (52.99- 111.23 ) and 39.30 (14.45-69.54) among total children, scattered children and daycare children, respectively; for every 10% increase in average relative humidity, the ER (95% CI ) values were 28.69 (12.22-47.56), 27.81 (12.01-45.84) and 24.42 (5.56-46.65), respectively. Conclusions The incidence level of HFMD among children in Jiujiang City is positively correlated with the average temperature and average relative humidity. Higher temperature and humidity are associated with an increased risk of excess HFMD incidence in scattered children compared to children in daycare centers.

Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Objective To explore factors associated with early postoperative hormonal remission in patients with prolactinoma and to develop prediction models based on clinical and radiological features. Methods Data from 107 patients with prolactinoma who underwent transsphenoidal surgery at The First People’s Hospital of Huai’an, Nanjing Medical University between January 2020 and December 2024 was collected, included general clinical characteristics, preoperative laboratory indicators, and imaging features. Based on whether early postoperative prolactin (PRL) levels normalized, patients were divided into a remission group (n=76) and a non-remission group (n=31). Univariate logistic regression was used for preliminary evaluation of candidate variables, followed by LASSO regression for feature selection. Multiple machine learning models were constructed, including logistic regression, random forest, support vector machine, K-nearest neighbors, naive Bayes, decision tree, neural network, and gradient boosting decision tree (GBDT). All models were trained and evaluated using ten-fold cross-validation, with comprehensive assessment of model performance based on the area under the ROC curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score. Results The maximum diameter of tumors in the non remission group was larger than that in the remission group (P=0.019), and the incidence of tumor stroke and preoperative PRL levels were significantly higher than those in the remission group (P＜0.001). Univariate analysis showed that sex, maximum tumor diameter, tumor stroke, and preoperative PRL levels were influencing factors for early postoperative hormone response in patients with prolactinoma (P＜0.05). The comparison results of machine learning models show that the neural network model performs the best (AUC=0.921) and has good clinical application value, followed by the GBDT model (AUC=0.893) and the support vector machine model (AUC=0.884). Other models also show certain predictive ability. Conclusions Sex, preoperative PRL levels, maximum tumor diameter, Hounsfield unit value, and tumor stroke are important factors affecting early hormone response after prolactinoma surgery. The machine learning model constructed based on the above variables has good predictive performance, and performs the best and has good clinical application value.

Objective:To evaluate the clinical features and risk factors of anastomotic leakage (AL) in patients with locally advanced rectal cancer (LARC) receiving neoadjuvant chemoradiotherapy (nCRT) followed by laparoscopic radical resection and proctocol ostomy.Method:Clinicla data of LARC patients receiving neoadjuvant chemoradiotherapy followed by laparoscopic radical resection and proctocol ostomy admitted to Peking Union Medical College Hospital between Jan 2019 and Oct 2023 was enrolled. According to the occurrence of AL, patients were divided into AL group and non-AL group.Results:After propersity matching score(PSM), there were 40 patients (33.4%) and 80 patients (66.6%) in the AL and non-AL group, respectively. The first-onset symptoms of AL were abnormal character and color of the drainage (23 cases, 57.5%) and fever (14 cases, 35.0%). About 82.5% of the AL were graded as B,and all 36 patients (90.0%) were managed consveratively by fully drainage anti-infection therapy. Logistic regression analysis indicated that tumor circumferential range more than 1/2 cycle ( OR=5.95, 95% CI:2.12-1.67, P=0.004), male ( OR=4.28, 95% CI:1.22-15.00, P=0.023) and high-ligation of Inferior mesenteric artery ( OR=8.08, 95% CI:1.86-37.78, P=0.006) were independent risk factors of AL. Conclusions:In this series, grade-B AL ranks the top of the incidence, and all were cured by conservative therapy. Special attention should be paid to those patients with the characteristics of male, tumor circumferential range more than 1/2 cycle, and high-ligation of inferior mesenteric artery.

OBJECTIVE To explore the potential mechanisms and bioactive compounds of licorice against COVID-19 based on a multidimensional interaction of"component-disease-symptom-target".METHODS Firstly,candidate target sets for licorice compo-nents were obtained from the ETCM2.0 database based on the Encyclopedia of Traditional Chinese Medicine,and the disease symp-toms and associated target sets for COVID-19 were derived from the GeneCards and HPO databases.And then a protein interaction network was constructed using the String database(version 12.0).By calculating topological eigenvalues and functional enrichment analysis,the potential mechanisms of action were explored.Combined with Schr?dinger molecular docking virtual screening,candidate pharmacodynamic substances were identified.Fluorescence resonance energy transfer was used for experimental verification.RESULTS Licorice might improve symptoms of COVID-19(fever,chest pain and so on)by regulating the imbalance of"immune-inflammation"network and signal transduction abnormalities during the development and progress of COVID-19,such as coronavirus disease-COVID-19,Toll-like receptor signaling pathway and NOD-like receptor signaling pathway.The components,such as Isos-chaftoside and Hesperidin,were identified to possess high binding affinity with the critical enzymes for viral replication.Isoschaftoside,Hesperidin,Isoliquiritin apioside and Vicenin-2 exhibited varying degrees of inhibition on the enzyme of 3CLpro at different concentra-tions while excluding the interference of the compounds' fluorescence.CONCLUSION Through experimental verification using a multidimensional interaction network of"component-disease-symptom-target",the key pharmacologically active substances of licorice in the fight against COVID-19 are preliminarily identified,and their mechanism of action through overall regulation is elucidated.

Objective: To analyze the status and trends of the disease burden of periodontal disease among women of reproductive age (15-49 years) in China from 1990 to 2021, and to provide a reference for the development of periodontal disease prevention and control strategies for women of reproductive age. Methods: Using the global burden of disease (GBD) data from 1990 to 2021, this study investigated the periodontal disease burden among women of reproductive age, including prevalence, incidence, disability-adjusted life years (DALYs), DALY rates, and their corresponding standardized indicators. Joinpoint 5.2.0.0 software was used for time trend analysis of DALYs, age-specific DALY rates, and annual average percentage change (AAPC) values. A log-linear regression model was used to test trends for DALYs and DALY rates. Results: Compared with 1990, the prevalence and incidence of periodontal disease among Chinese women in 2021 increased by 45.67% (per 100,000 people) and 29.29% (per 100,000 people), respectively. The distribution of periodontal disease among women (15-49 years) showed a continuous and rapid upward trend, with the growth rate increasing rapidly with age. The number of cases increased the fastest in the 45-49 age group, and the prevalence increased the fastest in the 35-44 age group. The incidence of periodontal disease continued to rise with age, with the fastest increase in the 35-44 age group among women of reproductive age. The Joinpoint regression model results showed that periodontal disease led to an expanding trend in the disease burden among women of reproductive age in China, with an AAPC of DALYs = 1.20% and an AAPC of DALY rate = 1.25% (P<0.001). Conclusion The periodontal disease burden among Chinese women aged 15-49 years showed a gradually increasing trend from 1990 to 2021.

Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective:To evaluate the clinical efficacy and impact on quality of life of the biofeedback (BF) therapy combined with the Wenyang Yiqi Prescription and self-efficacy interventions in patients with functional defecation disorders (FDD).Methods:A prospective, randomized controlled trial design was employed. A total of 128 FDD patients were selected from the Pelvic Floor Center of the Department of Proctology, Suzhou Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, between January 2021 and April 2023. These patients were randomly divided into two groups, with 64 cases in each group. Additionally, 41 historical control patients, who had received conventional BF training between June 2015 and January 2018 at the same center, were included for comparison. The historical control group received conventional BF therapy, the intervention group 1 combined BF therapy with self-efficacy interventions, and the intervention group 2 added the Wenyang Yiqi Prescription based on intervention group 1's treatment. All three groups underwent two treatment courses. Constipation symptom scores before and after treatment were performed; self-efficacy was assessed via the Self-Rated Abilities for Health Practices scale (SRAHP); health behaviors were evaluated using the Health-Promoting Lifestyle Profile (HPLP); anxiety and depression were evaluated through Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS); quality of life was measured through SF-36. Clinical efficacy was evaluated based on constipation symptom scores.Results:During the treatment period, seven patients dropped out due to personal reasons, leaving 61 patients in intervention group 1 and 60 patients in intervention group 2 for efficacy analysis.　The total effective rates were 80.32% (49/61) in intervention group 1, 83.33% (50/60) in intervention group 2, and 56.10% (23/41) in the historical control group. The total effective rates of both intervention groups were significantly higher than those in the historical control group ( χ2=7.06, 9.15; P=0.029, 0.010, respectively). After treatment, intervention group 2 showed significantly lower constipation-related straining scores [1 (1, 2) vs. 2 (1, 2), Z=-4.51] compared to intervention group 1 ( P<0.05). Additionally, intervention group 2 had lower scores for straining [1 (1, 2) vs. 2 (1, 2), Z=-3.15] and defecation time [1 (0, 1) vs. 1 (1, 2), Z=-3.13] compared to the historical control group ( P<0.05). Psychological comfort efficacy (19.13 ± 2.51 vs. 16.98 ± 1.86, t=5.36), health responsibility efficacy (23.63 ± 4.69 vs. 22.59 ± 3.05, t=2.06), and overall SRAHP scores (75.98 ± 4.44 vs. 72.33 ± 5.16, t=4.17) were higher in intervention group 2 compared to intervention group 1 ( P<0.05). The HPLP scores (79.33 ± 11.13 vs. 72.80 ± 9.20, t=3.10) of intervention group 2 were higher than those of the historical control group ( P<0.05). Emotional functioning scores (75.98 ± 18.45 vs. 68.92 ± 20.58 and 68.55 ± 18.21, F=20.91) in intervention group 2 were higher than in both intervention group 1 and the historical control group ( P<0.05). Conclusion:The combination of the Wenyang Yiqi Prescription with BF therapy and self-efficacy interventions effectively improves the clinical symptoms and quality of life in FDD patients.

Objective:To systematically review the current registered clinical study schemes in China regarding the combination of TCM and targeted drug therapy for lung cancer; To analyze their strengths and weaknesses; To provide reference for future study.Methods:Chinese Clinical Trial Registry for clinical study schemes combining TCM with targeted drug therapy for lung cancer treatment was retrieved from the inception to July 10, 2024. The general characteristics, study types, intervention measures, and outcome indicators of existing schemes were systematically summarized and analyzed.Results:A total of 15 studies were included, with the earliest study registered in 2013. Registration locations were concentrated in Shanghai, Guangdong, Tianjin, and Zhejiang. Among them, 9 studies received funding from local, national finance, or hospitals; 13 studies passed ethical review, and 12 included informed consent. The design schemes included 10 randomized controlled studies, 1 cohort study, 1 interventional single-arm study, and 3 observational studies. 6 studies had a sample size smaller than 100 cases, and most were single-center trials. Intervention measures primarily involved the combination of Chinese patent medicine or TCM with targeted drugs, with evaluation indicators mainly focusing on clinical symptoms and laboratory indicators. The setting of outcome indicators lacked a unified standard.Conclusions:Since 2013, clinical studies combining TCM with targeted drug therapy for lung cancer have been relatively methodologically sound but face challenges such as small sample sizes and a certain degree of regional concentration, leading to relatively insufficient representativeness. The future direction for improvement lies in multi-center, large-sample, and well-designed clinical trials. It is also necessary to establish a standardized and normalized system for evaluating outcomes. Integrating basic research to clarify the mechanisms of TCM can provide a theoretical basis for the combination of TCM and targeted drugs, which is conducive to enhancing the rigor and scientific nature of clinical trial design and promoting the formation of high-level evidence-based medicine.