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.

Objective To observe the clinical effects of the stereotaxic oblique-pulling manipulation under different mechanical parameters in the treatment of patients with lumbar disc herniation,and to explore the muscle-relaxing effects of the stereotaxic oblique-pulling manipulation and the traditional lumbar oblique-pulling manipula-tion in the treatment of lumbar disc herniation under the optimal mechanical parameters.Methods Using a three-factor,three-level orthogonal test method,27 LDH patients included in this study were randomly divided into 9 parameter groups,with 3 patients in each group,and were treated with different parameters of the stereotactic angled wrench method.3 factors were set up for the pressing force,the number of times,and the treatment interval,and each factor consisted of 3 levels,i.e.,pressing force:300～400 N,400～500 N,and 500～600 N;the number of times pressed 3 levels were set up:6 times,9 times,12 times;3 levels of treatment interval:1 day interval,2 days interval,3 days interval.After screening the optimal mechanical parameters through VAS,ODI and FDD evaluation indexes,94 patients were included and randomly divided into two groups;the treatment group was stereotaxic oblique-pulling manipulation under the configuration of optimal mechanical parameters,and the control group was the traditional lumbar oblique-pulling manipulation,and the changes of patients'VAS and ODI scores as well as the thickness of multifidus muscle and cross-sectional area before and after treatment were observed in the treatment of the two groups of patients.Through the comparison of lumbar multifidus muscle between healthy volunteers and patients with lumbar keyboard herniation,the characteristics of lumbar disc herniation multifidus muscle were clarified.The correlation between each observation index and parameter was analyzed by the statistical analysis software SPSS 26.0 to derive the optimal parameters for manipulative treatment.Results Orthogonal test analysis yielded that the order of influence on the efficacy was pressing force>treatment interval>pressing times,and the pressure interval with the best efficacy was:500～600 N,the number of times was 12 times,and the Treatment internal of 2 days.The degree of degeneration of lumbar multifidus muscle in patients with lumbar disc herniation was more obvious compared with that of healthy volunteers,and the difference was stati stically signifi-cant(P<0.05).Observed in both groups of patients with lumbar disc herniation after 6 weeks of treatment time,the VAS and ODI scores of both groups decreased significantly after treatment compared with those before treatment(P<0.05),with greater improvement in the treatment group.The results of the multifidus muscle showed that after treatment,the treatment group could significantly increase the resting thickness,contraction thickness,contraction rate and cross-sectional area of the multifidus muscle had significant changes(P<0.05),in which the contraction thickness,contraction rate before and after the treatment changes were more significant than the control group.Conclusions The stereotaxic oblique-pulling manipulation is effective in the treatment of lumbar disc herniation,in which the manipulation parameter pressure of 500～600 N,the number of presses 12 times,and the treatment interval of 2 days once for the treatment of lumbar disc herniation has better analgesia and improves the dysfunction effect.Compared with the traditional lumbar oblique-pulling manipulation,the stereotaxic oblique-pulling manipulation is better in improving the pain symptoms and dysfunction of patients with lumbar disc hernia-tion,as well as the resting thickness of the multifidus muscle,the contraction thickness,the contraction rate of change,and the cross-sectional area.

BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To explore the value of CT-based radiomics and machine learning in predicting the severity of community acquired pneumonia(CAP)in children.Methods The clinical and imaging data of 158 patients diagnosed with CAP in children were analyzed retrospectively.All patients were randomly divided into training set(n=110)and validation set(n=48)in a ratio of 7︰3.Radiomics features were outlined and extracted using 3D Slicer software,and feature selection was achieved using maximum relevance and minimum redundancy(MRMR)and least absolute shrinkage and selection operator(LASSO)algorithms.The construction of the nomogram model and the machine learning combined model was performed by combining clinical features and Radiomics score(Radscore),and its performance was evaluated and validated.Results The area under the curve(AUC)of the clinical model,the radiomics model and the nomogram model in the validation set were classified as 0.82,0.86 and 0.91,respectively.The AUC of the combined multi-layer perceptron(MLP),random forest(RF),and adaptive boosting(ADB)models were 0.926,0.934 and 0.917,respectively in the validation set.Conclusion Radiomics combined with clinical data is expected to be a novel predictor of the severity of CAP in children.MLP,RF and ABD machine learning algorithms can further enable model performance.

Objective To construct mouse models of vaccinia virus infection using C57BL/6N and BALB/C mice infected with vaccinia virus VR-1354(WR(NIH TC-adapted)),and to compare the differences between the models in the two mouse strains.Methods Vaccinia virus VR-1354 was amplified,concentrated,and titrated,according to conventional method.The median lethal doses(LD50)of vaccinia virus V R-1354 for C57BL/6N and BALB/C mice were determined,respectively,and mice from the two strains were infected with the respective LD50.Lung tissues from control and experimental mice were removed for hematoxylin and eosin staining on days 3,7,and 14,and changes in the virus load in the lung tissues were measured at the same times.Results The titer of the amplified vaccinia virus VR-1354 was 3×108 plaque forming units(PFU)/mL.The LD50 values in C57BL/6N and BALB/C mice were 2.5×103and BALB/C 2.8×103PFU,respectively.After infecting mice from both strains with 2.5× 103 PFU of vaccinia virus VR 1354,lung tissue lesions worsened with increasing infection time,but the symptoms of the mice tended to recover after day 7.The virus loads in lung tissues began to increase on day 3 in both strains,peaked on day 7,and then gradually decreased.Conclusions C57BL/6N and BALB/C mouse models infected with vaccinia virus VR-1354 were established successfully.The virus can cause obvious lesions in mouse lung tissues,including inflammatory cell infiltration and alveolar cavity fluid exudation.The degree of disease onset and susceptibility differed between the two mouse strains,with C57BL/6N mice showing higher susceptibility to this virus than BALB/C mice.

Pancreaticoduodenectomy (PD) is a primary surgical approach for treating mali-gnant tumors of the pancreatic head and the periampullary region. With the advance in medical technology in recent years, the long-term survival rate of patients undergoing PD has significantly improved, and the incidence of early perioperative complications has markedly decreased. However, current researches predominantly focuse on early postoperative complications, while, limited studies addressing long-term complications. Long-term complications after PD have a significant impact on patients′ quality of life and long-term survival. This authors systematically summarize the common long-term complications following PD, and explore their mechanisms, clinical manifestations, dia-gnostic methods, and treatment strategies, aiming to provide a reference for clinical practice.