ObjectiveA mouse model of vaccinia virus Tiantan strain (VTT)-induced encephalopathy was developed using AG6 mice. MethodsVTT was amplified by infecting Vero cells at a multiplicity of infection (MOI) of 0.01, followed by concentration and titration. After 72 h of incubation, virus-containing cells were collected and subjected to concentration. The concentrated viral suspension was serially diluted (10-fold dilutions) and added to 6-well plates containing confluent Vero cell monolayers for plaque assay. The number of plaques formed in each well was counted, and the virus titer was calculated based on the dilution factor. Fourteen 5-6-week-old AG6 mice (half male and half female, housed separately by sex) were randomly divided into a control group (n=3, PBS), a low-dose group (n=6, 1×10⁵ PFU), and a high-dose group (n=5, 5×10⁵ PFU). The mice were anesthetized by isoflurane inhalation and then infected via intranasal instillation. The mental state of the mice in each group was observed daily, and the body weight and mortality were recorded. On day 13 post-infection, 2% Evans Blue (4 mL/kg body weight) was administered via tail vein injection to assess blood-brain barrier (BBB) disruption. Subsequently, brain tissue samples were collected for immunofluorescence analysis to evaluate the activation of astrocytes and microglia. ResultsThe titer of purified VTT was 1×10⁷ PFU/mL. Compared with the control group, mice in the low-dose group showed no significant change in body weight, and no lethality was observed. In contrast, mice in the high-dose group exhibited significant weight loss starting on day 5 post-infection (P<0.05), accompanied by lethality. On day 13 post-infection, no Evans Blue extravasation was detected in the brain tissues of the low-dose group, while the olfactory bulb region of the high-dose group displayed distinct blue staining, indicating disruption of the BBB. Immunofluorescence analysis revealed no significant proliferation of astrocytes and microglia in the olfactory bulb region of the low-dose group on day 13 post-infection. In contrast, marked activation of glial cells was observable in the high-dose group. ConclusionAn animal model of VTT-induced encephalopathy in AG6 mice is successfully established, characterized by BBB disruption and reactive gliosis specifically localized to the olfactory bulb region, manifested as astrocytic and microglial proliferation.

Background Prehospital emergency medical personnel (PEMP) are exposed to long-term high-pressure work, which can exacerbate psychological distress and impair job satisfaction and sleep quality. However, in-depth research on the interactions among these factors is lacking. Objective To assess the status of psychological distress, job satisfaction, and sleep quality of PEMP in Guangzhou and to explore the mediating role of sleep quality in the relationship between psychological distress and job satisfaction. Methods From February to May 2025, 1085 PEMP from "120" emergency network hospitals in Guangzhou were selected using convenience sampling. Data were collected via the General Information Questionnaire, Kessler Psychological Distress Scale, Minnesota Satisfaction Questionnaire, and Pittsburgh Sleep Quality Index. Statistical analyses were performed using SPSS 25.0, and The mediation model of sleep quality in linking psychological distress and job satisfaction was constructed using AMOS 28.0. The bias-corrected Bootstrap method was employed to assessed the significance of the mediating effect. Results A total of 1063 valid responses were received (97.97% valid response rate). The mean scores were: psychological distress (27.99±10.75), job satisfaction (69.45±15.84), and sleep quality (9.82±4.47). Significant differences in the three scores were found across gender, age, monthly night shift frequency, and hospital grade (P<0.05). Higher job satisfaction was linked to lower psychological distress and better sleep quality and its dimensions, while psychological distress directly correlated with poorer sleep quality (P<0.01). Sleep quality partially mediated the relationship between psychological distress and job satisfaction, with a mediating effect of −0.195, accounting for 43.62% of the total effect. Conclusion The participants report moderate psychological distress, moderate-to-high job satisfaction, and poor sleep quality. Psychological distress directly affects job satisfaction and indirectly through its impact on sleep quality. Interventions aimed at improving sleep health and mental health are essential to improve personnel well-being and work efficiency.

Background Prehospital emergency medical personnel (PEMP) are exposed to long-term high-pressure work, which can exacerbate psychological distress and impair job satisfaction and sleep quality. However, in-depth research on the interactions among these factors is lacking. Objective To assess the status of psychological distress, job satisfaction, and sleep quality of PEMP in Guangzhou and to explore the mediating role of sleep quality in the relationship between psychological distress and job satisfaction. Methods From February to May 2025, 1085 PEMP from "120" emergency network hospitals in Guangzhou were selected using convenience sampling. Data were collected via the General Information Questionnaire, Kessler Psychological Distress Scale, Minnesota Satisfaction Questionnaire, and Pittsburgh Sleep Quality Index. Statistical analyses were performed using SPSS 25.0, and The mediation model of sleep quality in linking psychological distress and job satisfaction was constructed using AMOS 28.0. The bias-corrected Bootstrap method was employed to assessed the significance of the mediating effect. Results A total of 1063 valid responses were received (97.97% valid response rate). The mean scores were: psychological distress (27.99±10.75), job satisfaction (69.45±15.84), and sleep quality (9.82±4.47). Significant differences in the three scores were found across gender, age, monthly night shift frequency, and hospital grade (P<0.05). Higher job satisfaction was linked to lower psychological distress and better sleep quality and its dimensions, while psychological distress directly correlated with poorer sleep quality (P<0.01). Sleep quality partially mediated the relationship between psychological distress and job satisfaction, with a mediating effect of −0.195, accounting for 43.62% of the total effect. Conclusion The participants report moderate psychological distress, moderate-to-high job satisfaction, and poor sleep quality. Psychological distress directly affects job satisfaction and indirectly through its impact on sleep quality. Interventions aimed at improving sleep health and mental health are essential to improve personnel well-being and work efficiency.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

BACKGROUND: Pancreatic cancer is a lethal malignancy prone to gemcitabine resistance. The single-strand selective monofunctional uracil DNA glycosylase (SMUG1), which is responsible for initiating base excision repair, has been reported to predict the outcomes of different cancer types. However, the function of SMUG1 in pancreatic cancer is still unclear. METHODS: Gene and protein expression of SMUG1 as well as survival outcomes were assessed by bioinformatic analysis and verified in a cohort from Fudan University Shanghai Cancer Center. Subsequently, the effect of SMUG1 on proliferation, cell cycle, and migration abilities of SMUG1 cells were detected in vitro . DNA damage repair, apoptosis, and gemcitabine resistance were also tested. RNA sequencing was performed to determine the differentially expressed genes and signaling pathways, followed by quantitative real-time polymerase chain reaction and Western blotting verification. The cancer-promoting effect of forkhead box Q1 (FOXQ1) and SMUG1 on the ubiquitylation of myelocytomatosis oncogene (c-Myc) was also evaluated. Finally, a xenograft model was established to verify the results. RESULTS: SMUG1 was highly expressed in pancreatic tumor tissues and cells, which also predicted a poor prognosis. Downregulation of SMUG1 inhibited the proliferation, G1 to S transition, migration, and DNA damage repair ability against gemcitabine in pancreatic cancer cells. SMUG1 exerted its function by binding with FOXQ1 to activate the Protein Kinase B (AKT)/p21 and p27 pathway. Moreover, SMUG1 also stabilized the c-Myc protein via AKT signaling in pancreatic cancer cells. CONCLUSIONS SMUG1 promotes proliferation, migration, gemcitabine resistance, and c-Myc protein stability in pancreatic cancer via protein kinase B signaling through binding with FOXQ1. Furthermore, SMUG1 may be a new potential prognostic and gemcitabine resistance predictor in pancreatic ductal adenocarcinoma.
Humans ; Pancreatic Neoplasms/pathology* ; Forkhead Transcription Factors/genetics* ; Signal Transduction/genetics* ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation/physiology* ; Mice ; Uracil-DNA Glycosidase/genetics* ; Female ; Male ; Gemcitabine ; Mice, Nude ; Apoptosis/physiology* ; Deoxycytidine/analogs & derivatives* ; Cell Movement/genetics*

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

BACKGROUND: Lung cancer has the highest mortality rate among all malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancers. Lobectomy and lymph node dissection are one of the most important treatment methods, and lymph node dissection, as an important part, has attracted much attention. And its mode and scope of dissection may affect postoperative complications, particularly the occurrence of chronic cough. The aim of this study is to investigate the effect of lymph node dissection on postoperative chronic cough in patients with NSCLC undergoing lobectomy, and to provide clinical evidence for optimizing surgical strategy and reducing postoperative chronic cough. METHODS: A retrospective analysis was conducted on the clinical data of 365 NSCLC patients who underwent lobectomy at the First Affiliated Hospital of University of Science and Technology of China from December 2020 to December 2023. The relationship between clinical characteristics and postoperative chronic cough was analyzed. The Chinese version of the Leicester Cough Questionnaire (LCQ-MC) scores were collected from the patients at 2 time points: 1 day before surgery and 8 weeks after surgery. Patients were divided according to lymph node dissection methods, to explore the relationship between lymph node dissection and chronic cough after lobectomy. Additionally, patients were divided into chronic cough and non-chronic cough groups based on the presence of postoperative chronic cough, to investigate whether perioperative data, lymph node dissection methods, and lymph node dissection regions were influencing factors. RESULTS: Patients undergoing lobectomy were more likely to have chronic cough after surgery in the systematic lymph node dissection group than in the lymph node sampling group (P<0.05). LCQ-MC scale evaluation showed that the psychological, physiological, social and total score of the patients in systematic lymph node dissection group were significantly lower than those in lymph node sampling group (P<0.05). Multivariate analysis showed that anesthesia time, operation site, lymph node dissection method, whether to perform upper mediastinal lymph node dissection, number of upper mediastinal lymph node dissection, whether to perform lower mediastinal lymph node dissection and total number of lymph node dissection were independent risk factors for postoperative chronic cough in NSCLC patients (P<0.05). CONCLUSIONS When NSCLC patients underwent lobectomy, lymph node sampling was associated with a significantly lower risk of chronic cough than systematic lymph node dissection. Dissecting lymph nodes in the upper and lower mediastinal regions and the number of lymph nodes dissected may increase the risk of postoperative cough and reduce the quality of life of patients after surgery.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Female ; Lung Neoplasms/surgery* ; Middle Aged ; Cough/etiology* ; Retrospective Studies ; Lymph Node Excision/methods* ; Aged ; Chronic Disease ; Postoperative Complications/etiology* ; Adult ; Lymph Nodes/surgery* ; Pneumonectomy/adverse effects* ; Chronic Cough

Objective:To discuss the clinical efficacy of low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess for the treatment of congenital pyriform sinus fistula （CPSF） in the acute inflammatory period of children. Methods:Clinical data of 30 patients with CPSF in the acute inflammatory period who received low-temperature radiofrequency ablation assisted by endoscopy under laryngoscope, combined with resection and drainage of cervical abscess, from January 2018 to December 2023 were reviewed. After the operation, patients were followed up closely at different stages. All patients underwent color Doppler ultrasound and electronic laryngoscopy, and the results were analyzed. Results:All 30 children successfully completed the surgery without pharyngeal fistula, dysphagia, perifistula, or distal fistula infection, and the incision in the neck healed well. The follow-up survey ranged from 6 months to 2 years, and no recurrences were observed. Conclusion:Low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess is a promising method for treating CPSF in the acute inflammatory period. It is less traumatic, simple, safe, has a significant curative effect, and a low recurrence rate. This approach can be used as a supplementary operation for CPSF in children and provides a new way for clinical treatment.
Humans ; Pyriform Sinus/abnormalities* ; Abscess/surgery* ; Drainage ; Fistula/congenital* ; Female ; Male ; Child ; Radiofrequency Ablation ; Treatment Outcome ; Postoperative Period ; Endoscopy ; Laryngoscopy ; Inflammation ; Child, Preschool