ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

BackgroundAnxiety exhibits a rising prevalence among college students. Investigating the mechanisms through which family function relates to anxiety and examining the moderating role of emotion regulation strategies within this context hold substantial implications for promoting mental health among college students. However， existing research has not sufficiently elucidated the complex interplay among family function， emotion regulation， and anxiety among college students. Further research is warranted to clarify the underlying mechanisms linking family function to anxiety outcomes and to examine the potential moderating role of emotion regulation strategies in this causal pathway. ObjectiveTo explore the relationship between family function and anxiety among lower-grade college students， and to validate the moderating role of emotion regulation strategies in this relationship， thereby offering evidence-based insights for anxiety reduction interventions in this population. MethodsIn March 2023， a total of 1 980 first- and second-year students from a comprehensive university in Shanghai were selected using the cluster sampling method. A self-designed demographic questionnaire， the Emotion Regulation Questionnaire （ERQ）， the Family Adaptability and Cohesion Evaluation Scale Ⅱ-Chinese Version （FACES Ⅱ-CV）， and the Symptom Checklist-90 （SCL-90） were utilized for assessment. Pearson correlation analysis and Spearman correlation analysis were employed to test the correlations of each variable. Hierarchical linear regression analysis was conducted to certify the moderating role of emotion regulation strategies in the relationship between family function and anxiety. ResultsCompared with female students， male students scored significantly lower on ERQ cognitive reappraisal （t=-5.793， P<0.01） but significantly higher on ERQ expressive suppression （t=8.359， P<0.01）. For lower-grade college students， scores on adaptability and cohesion subscales of FACES Ⅱ-CV showed a positive association with cognitive reappraisal in ERQ （r=0.251， 0.302， P<0.01）， while simultaneously displaying negative correlations with both expressive suppression in ERQ （r=-0.113， -0.154， P<0.01） and anxiety in SCL-90 （r=-0.243， -0.202， P<0.01）. Notably， anxiety scores in SCL-90 were inversely related to cognitive reappraisal scores in ERQ （r=-0.159， P<0.01） but directly associated with expressive suppression scores in ERQ （r=0.171， P<0.01）. Hierarchical regression analysis indicated that cognitive reappraisal significantly moderated the relationship between family cohesion and anxiety （β=-0.421， P<0.01）. ConclusionThe cognitive reappraisal strategy serves as a moderator in the relationship between family cohesion and anxiety， potentially mitigating the escalation of anxiety levels associated with family dysfunction. ［Funded by Science and Technology Development Fund of Shanghai Pudong New Area （number， PKJ2023-Y21）］

ObjectiveTo explore the potential mechanism of Xiaoqinglongtang（XQL） in the prevention and treatment of high altitude pulmonary edema（HAPE） by network pharmacology， molecular docking， and molecular dynamics simulation， and to verify it by in vivo animal model. MethodsIn this study， the active ingredients， drug targets， and HAPE-related targets of XQL were collected from BATMAN-TCM， GeneCards， and Online Mendelian Inheritance in Man（OMIM） databases. The protein-protein interaction（PPI） network was constructed by using intersection targets， and the core targets were screened and visualized by Cytoscape software. Functional annotation and pathway analysis of the intersection targets were performed by gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） functional enrichment. AutoDock and GROMACS were used to evaluate the binding ability of active ingredients to key targets. In the experimental verification part， a mouse model of HAPE induced by hypobaric hypoxia（simulated 6 000 m altitude for 48 h） was established. The control effect was evaluated by hematoxylin-eosin（HE） staining， lung tissue water content， lung tissue wet/dry weight ratio， real-time quantitative polymerase chain reaction（Real-time PCR） detection of gene expression levels， and immunohistochemistry and Western blot detection of key protein expression. ResultsA total of 355 active ingredients of XQL， 2 142 targets， 716 HAPE-related targets， and 236 intersection targets were obtained by network pharmacology analysis. Key core targets such as interleukin （IL）-6， tumor necrosis factor （TNF）， protein kinase B1 （Akt1）， and hypoxia-inducible factor-1α （HIF-1α） were screened. The results of GO analysis of common targets involved 738 biological processes（BP）， 72 cellular components（CC）， and 135 molecular functions（MF）. KEGG analysis effectively enriched two important signaling pathways： Phosphoinositol 3-kinase （PI3K）/Akt and HIF-1α. The results of molecular docking and molecular dynamics simulation showed that the screened active ingredients had good binding ability with key targets. In the HAPE model induced by hypobaric hypoxia（6 000 m， 48 h）， the lung tissue water content， lung tissue wet/dry weight ratio， and pathological injury score of the model group were significantly increased（P<0.01）， accompanied by exudation of a large number of red blood cells in the alveoli and alveolar interstitium， a significant increase in inflammatory cells， a significant widening of the alveolar septum， and mutual fusion between the alveoli. The XQL administration group significantly improved the above pathological changes（P<0.01）. The results of inflammatory factor expression showed that compared with the control group， the model group showed significantly up-regulated expression of TNF-α， IL-6， and IL-1β in the lung tissue（P<0.01）. Compared with the model group， the XQL administration group had significantly decreased expression of inflammatory factors（P<0.05， P<0.01）. The mRNA expression of key pathway related genes PI3K， Akt1， mammalian target of rapamycin（mTOR）， and HIF-1α was significantly increased in the model group（P<0.01）， and decreased in a concentration-dependent manner after XQL administration（P<0.05， P<0.01）. The expression levels of key proteins PI3K， phosphorylation（p）-PI3K， Akt1， p-Akt1， mTOR， p-mTOR， and HIF-1α in lung tissue were analyzed by immunohistochemistry and Western blot. Compared with the blank group， the model group showed increased expression of key proteins（P<0.05， P<0.01）. Compared with the model group， the XQL administration group exhibited decreased expression of key proteins（P<0.05， P<0.01）. ConclusionXQL can reduce lung inflammation and improve HAPE. The mechanism may be related to the regulation of PI3K/Akt/mTOR and HIF-1α pathways. This study provides a new idea and a theoretical basis for the treatment of HAPE with XQL.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

OBJECTIVE To investigate the mechanism of Qushi huoxue decoction in improving metabolic-associated fatty liver disease （MAFLD） based on the AMP-activated protein kinase/mammalian target of rapamycin/UNC-51-like kinase 1 （AMPK/mTOR/ULK1） autophagy signaling pathway.METHODS Male C57BL/6J mice were randomly divided into normal group， model group， and low-， medium-， and high-dose Qushi huoxue decoction groups [4.10， 8.20， 16.40 mg/（g·d）]， with 10 mice in each group. Except for the normal group， mice in the other groups were fed a high-fat diet for 12 weeks to establish the MAFLD model. Starting 24 hours after modeling， mice in each group were administered the drug solution or normal saline once daily for 6 consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， alanine transaminase （ALT）， aspartate transferase （AST）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected according to the kit instructions. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe pathological changes in mouse liver tissue. Western blot and immunofluorescence staining were used to detect the expression and positive protein expression related to the AMPK/mTOR/ULK1 autophagy signaling pathway.RESULTS Compared with the normal group， the serum levels of TC， TG， ALT， AST， and LDL-C in the model group were significantly increased， while the HDL-C level was significantly decreased （ P ＜0.01）. HE staining showed obvious steatosis in hepatocytes of the model group， and oil red O staining showed a large amount of lipid droplet accumulation in liver tissue. Western blot and immunofluorescence staining results showed that the expression levels of p-mTOR/mTOR and p62 proteins， as well as the relative fluorescence intensities of p-mTOR and p62 proteins in liver tissue of the model group， were significantly increased/enhanced （ P ＜0.01）， while the expression levels of p-AMPK/AMPK， ULK1， and microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ） proteins， as well as the relative fluorescence intensities of p-AMPK and LC3 proteins， were significantly decreased/weakened （ P ＜0.01）. After intervention with Qushi huoxue decoction， the above pathological changes and abnormal indicators in liver tissue of mice in the low-， medium-， and high-dose groups were significantly reversed， with most indicators showing statistically significant differences （ P ＜0.05 or P ＜0.01）.CONCLUSIONS Qushi huoxue decoction can significantly improve liver pathology， blood lipid levels， and liver function in MAFLD model mice； this improvement may be achieved through the activation of the AMPK/mTOR/ULK1 autophagy signaling pathway.

OBJECTIVE To provide guidance for pharmaceutical care in patients with severe Cryptococcus gattii infections.METHODS Clinical pharmacists participated in the diagnosis and treatment of a male patient with disseminated Cryptococcus gattii infection （involving the lungs and central nervous system）. Given the patient’s poor response to initial therapy， the clinical pharmacists， based on antimicrobial susceptibility test results， recommended voriconazole as an alternative azole. In response to refractory hypokalemia caused by liposomal amphotericin B， the clinical pharmacists assisted the physician in developing an intensive potassium replacement regimen. Regarding the interaction between voriconazole and nifedipine， the clinical pharmacists proactively identified the risk and intensified monitoring of the patient’s blood pressure. In response to the onset of hepatitis C during treatment， the clinical pharmacists thoroughly weighed the priority of infection treatment and recommended temporarily postponing antiviral therapy for hepatitis C. For the individualized use of voriconazole， the clinical pharmacists repeatedly performed therapeutic drug monitoring （TDM）. Regarding the patient’s poor lesion resolution， the clinical pharmacists participated in multidisciplinary team discussions to clarify the indications for surgery.RESULTS The physician adopted the clinical pharmacists’ recommendations. Following pharmacological treatment and surgical intervention， the patient’s condition stabilized， and he was discharged while still on medication.CONCLUSIONS For severe Cryptococcus gattii infections， clinical pharmacists should focus on pathogen characteristics， strengthen adverse reaction management， pay close attention to drug interactions， conduct TDM， and actively participate in multidisciplinary team collaboration to ensure the safety and efficacy of patient treatment.

Objective: To delineate the epidemiologic profile of rifampicin resistant pulmonary tuberculosis (RR-PTB) among students in Chongqing, so as to provide evidence for effectively controlling RR-PTB outbreaks in schools. Methods: Individual level surveillance records of 395 student RR-PTB cases reported from 2015 to 2024 were extracted from the China Information System for Disease Control and Prevention. The Joinpoint regression analysis was employed to quantify temporal trends in the registration rate of student RR-PTB cases, and the comparison of RR-PTB registration rates with different demographic characteristics and different regions was performed using Chi-square test. Results: From 2015 to 2024, a total of 395 student RR-PTB cases were identified, with the registration rate ranged from 0.07 per 100 000 to 1.47 per 100 000, showed a fluctuating upward trend ( AAPC= 35.22%, t =4.13, P <0.01). A turning point was detected in 2017, rates rose during 2015-2017 (APC=295.23%， t =4.62， P < 0.01 ) and plateaued thereafter (APC=-0.47%， t =-0.12， P =0.91). The proportion of RR-PTB cases occurring among students increased both among all RR-PTB cases (1.54% in 2015, 7.48% in 2024) and all student pulmonary tuberculosis cases (0.20% in 2015, 7.17% in 2024), with significant linear trends ( χ 2 trend =33.55,159.98, both P <0.01). The majority of cases were enrolled in senior high school (50.38%), classified as retreatment (53.92%), of Han ethnicity (75.95%), and diagnosed with multidrug resistant tuberculosis(53.16%). There were significant differences in the composition of different ethnicity, registration category and resistance pattern between different years( χ 2=23.47, 17.23, 59.64，all P <0.05). The South-Eastern Wuling Mountainous Region exhibited the highest notification rate (3.96 per 100 000), whereas the western region had the lowest rate ( 0.47 per 100 000). County level jurisdictions reported higher rates than district level ones (2.16 per 100 000 vs 0.63 per 100 000 ). Statistically significant differences were observed in the RR-PTB reported rates among students across different districts and counties( χ 2=418.05,167.05,both P <0.01). Conclusions From 2015 to 2024, the registration rate of detected student RR-PTB cases in Chongqing showed an increasing trend. Students have become one of the key populations for drug resistant TB prevention and control. Intensified health education and active case finding should be implemented to enhance proactive surveillance capabilities.

Objective : To explore the role of semaphoring 6d(SEMA6D) in the malignant progression of triple-negative breast cancer(TNBC). Methods : Bioinformatics and Immunohistochemistry(IHC) were used to analyze the expression level of SEMA6D in TNBC and paracancer non-tumor tissues and its relationship with patients′ clinicopathological features. MDA-MB-231 cell line stably knocking down the expression of SEMA6D was constructed, and the effects of SEMA6D on migration and invasion of TNBC cells were investigated by Wound-healing assays and Transwell assays. cBioPortal and GEPIA2 databases were used to screen out the gene negatively associated with it, namely aurora kinase A(AURKA). Bioinformatics and IHC were used to analyze the expression level of AURKA in TNBC and paracancer non-tumor tissues and its relationship with patients' clinicopathological features. Western blot assay was used to analyze the expression of AURKA and the effect of epithelial-mesenchymal transition(EMT) makers Claudin-1, N-cadherin and Vimentin after knocking downSEMA6D. Results: Bioinformatics analysis and IHC results showed that the expression of SEMA6D in TNBC tissues was significantly lower than that in paracancer non-tumor tissues(bothP<0.05). The expression of AURKA in TNBC tissues was significantly higher than that in paracancer non-tumor tissues(bothP<0.05), SEMA6D and AURKA were significantly negatively correlated in TNBC(P<0.01). Both low expression of SEMA6D and high expression of AURKA were positively correlated with tumor size, tumor histological grade, clinical stage and lymph node metastasis in TNBC patients(allP<0.05). The knockdown ofSEMA6Dsignificantly promoted the migration and invasion ability of TNBC cells(bothP<0.01). Western blot results showed that the knockdown ofSEMA6Dupregulated AURKA expression, promoted the expression of N-cadherin and Vimentin, and inhibited the expression of Claudin-1 in tumor cells. Conclusion Down-regulation of SEMA6D expression in TNBC may be involved in the malignant progression of TNBC through up-regulation of AURKA expression and promotion of EMT.

Objective To investigate the status quo of health management behaviors in elderly patients with type 2 diabetes mellitus(T2DM)complicating chronic complications and the influencing factors based on health ecology theory.Methods The convenience sampling method was used to select elderly patients with T2DM complicating chronic complications in the Shanghai City from January to July 2022 as the respondents.Based on the health ecology theory,the five aspects of personality traits,psychological and behavioral traits,family and community interpersonal networks,living and working conditions and policy environment were in-vestigated.The Pearson correlation coefficient was used to analyze the correlation of various variables.The hi-erarchical linear regression was used to analyze the influencing factors of health management behaviors in eld-erly patients with T2DM complicating chronic complications.Results A total of 272 questionnaires were dis-tributed and 264 valid questionnaires were recovered,with an effective recovery rate of 97.06％(264/272).There were statistically significant differences in DSMB-Oscores among the patients with different chronic complications number,sleep quality,per capita monthly household income and medical payment methods(P＜0.05).The DSMB-Oscore in elderly patients with T2DM complicating chronic complications was positively correlated with HLSCP,DES,PACIC and CIRS scores(P＜0.05),and negatively correlated with the PAID-5 score(P＜0.05).Conclusion The health management behaviors of elderly patients with T2DM complicating chronic complications is jointly affected and acted by many factors,and it is necessary to identify and manage the related influencing factors from different aspects and different levels.

Objective To compare the positioning errors,required planning target volume(PTV)outer expansion boundary and three-dimensional displacement of two different positioning fixation devices CIVCO Uni-frame carbon fiber adjustable angle head frame and domestic integrated board in radiotherapy for the pa-tients with head tumor,and to investigate the application value of CIVCO headrest in the positioning of head tumor radiotherpay.Methods The clinical data of 82 patients with head tumors who underwent radiotherapy in this hospital from January to December 2023 were analyzed retrospectively.The patients were divided into the adjustable angle head frame group and integrated plate group,41 cases in each group.Both groups were fixed with U-shaped thermoplastic head film.Radiotherapy was performed by using ELEKTA infinity linear accelerator.The cone beam computed tomography(CBCT)image guidance was used,combined with bone reg-istration and manual calibration to obtain the patient positioning errors in three directions:X axis,Y axis and Z axis.The positioning error data of each CBCT was recorded;based on the PTV outward expansion boundary formula(2.5∑+0.7σ),the PTV outward expansion boundaries required by the two fixation devices in all di-rections for the treatment of head tumors were calculated;the 3-dimensional spatial displacement was calculat-ed based on the patient's single radiotherapy positioning error.Results The absolute positioning errors in the X,Y,and Z directions of the adjustable angle head frame group were 0.13(0.07,0.22),0.16(0.16,0.27),0.10(0.05,0.18)cm respectively,which in the integrated board group were 0.14(0.07,0.24),0.18(0.08,0.32),0.09(0.04,0.10)cm respectively.The absolute error of the Y direction in the adjustable angle head frame group was smaller than that of the integrated board group(P=0.006),and the difference in the relative error between the two groups was not statistically significant(P＞0.05).According to the PTV expansion formula,the calculated expansion boundaries of the X,Y,and Z directions in the adjustable head frame group were 0.24,0.30,0.22 cm,which in the integrated plate group were 0.21,0.36,0.21 cm,respectively.The three-dimensional space comprehensive positioning error value could be calculated by the formula calculation using the positioning error values in three directions.The mean values of the three-dimensional space positio-ning errors of the adjustable angle headstock group and domestic integrated plate group were 0.320 cm and 0.340 cm respectively,there was no statistically significant difference between the two groups.Conclusion The absolute error in Y direction and the median value of three-dimensional displacement of the CIVCO adjustable angle head rest are smaller than those of the domestic integrated plate,which is worthy of clinical promoted applica-tion if conditions permit.