OBJECTIVE To explore the improvine mechanism of Yifei xuanfei jiangzhuo formula （YFXF） on vascular dementia （VAD） model rats based on the growth factor receptor-bound protein 2 （GRB2）/extracellular signal-regulated kinase （ERK）/cardiolipin synthase 1 （CRLS1） pathway. METHODS VAD rat model was established by permanent bilateral common carotid artery ligation. Forty-eight successfully modeled rats were randomly divided into the model group （normal saline）， donepezil hydrochloride group （positive control group， 0.2 g/kg）， and YFXF low- and high-dose groups （12.18 and 24.36 g/kg， calculated based on the total amount of crude drug）， respectively. In addition， a sham operation group （normal saline） was set up. There were 12 rats in each group. Daily intragastric administration of drug or normal saline was performed for 30 consecutive days. After the last administration， the spatial cognitive ability of the rats was evaluated， the pathological morphology of the hippocampus was observed， the contents of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） in serum were detected， the expression levels of GRB2/ERK/CRLS1 pathway-related proteins and the mRNA levels of GRB2， CRLS1， NADH dehydrogenase subunit 1（ND1）， Tafazzin （TAZ）， phospholipid scramblase 3（PLSCR3） and the ATP content in hippocampal tissue were measured. RESULTS Compared with the sham operation group， the escape latency of rats in the model group was significantly prolonged （ P ＜0.05）， and the number of crossing platform was significantly reduced （ P ＜0.05）， while the number of pyramidal cells and Nissl bodies in the hippocampus decreased sharply； the content of TNF-α in serum was significantly increased （ P ＜0.05）， and the content of IL-4 was significantly decreased （ P ＜0.05）； the expression levels of GRB2 and CRLS1 proteins， the phosphorylation level of ERK protein， the relative expression levels of GRB2， CRLS1，ND1， TAZ， and PLSCR3 mRNA， and the content of ATP in hippocampal tissue were significantly decreased （ P ＜0.05）. Compared with the model group， the above pathological changes in the hippocampal tissue of each administration group were alleviated， and the quantitative indicators were significantly restored （ P ＜0.05）. CONCLUSIONS YFXF may improve hippocampal neuron injury in VAD rats by activating the GRB2/ERK/CRLS1 pathway, maintaining cardiolipin homeostasis， and improving mitochondrial energy metabolism.

Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Objective:To study the comprehensive surgical treatment of brucellosis with chest wall cysts as the main manifestation.Methods:Retrospective analysis was made on the general information epidemiological characteristics, clinical manifestations, laboratory examinations, imaging examinations, treatment and outcomes of five patients with brucellosis mainly manifested by chest wall cysts admitted to the 948 Hospital of the People's Liberation Army from July 2019 to June 2022.Results:Among the 5 patients, there were 4 males and 1 female, aged between 23 and 64 years old, with a clear history of contact with cattle and sheep. The main clinical manifestation was painless cystic masses on the chest wall. Both the serum tiger red plate agglutination test (RBPT) and the test tube agglutination test (SAT) were positive. Four cases were infected with Brucella and one case was infected with Actinobacillus pleuropneumoniae (considered as Brucella infection based on the overall condition). All patients exhibited abnormal chest wall signals (manifesting as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging) on magnetic resonance imaging(MRI), and were ultimately diagnosed with brucellosis presenting predominantly as chest wall cysts. After complete removal of the chest wall cyst through surgery, a combination treatment of rifampicin capsules and doxycycline hyclate tablets was given for 6 weeks. There were no significant adverse reactions and the wound healed in one stage. During the postoperative follow-up period of 11 - 40 months, MRI reexamination demonstrated no evidence of chest wall cyst recurrence, and all SAT results were negative. Conclusions:Patients with brucellosis presenting as chest wall cysts are clinically rare and lack specific symptoms. Surgical resection of the affected lesion combined with early, standardized, combined, and full course antimicrobial therapy results in a good prognosis for the patient.

Objective The study explored the psychological help-seeking experiences of adolescents with mood disorder,so as to provide references for healthcare professionals to carry out relevant interventions to facilitate adolescents'early access to mental health services.Methods A qualitative research was adopted,and 14 adolescents with mood disorder admitted to a tertiary hospital in Lanzhou City from December 2023 to March 2024 were interviewed by semi-structured interviews.The data was analyzed by Colaizzi seven-step method.Results 3 themes were extracted,including long and tortuous help-seeking journey(maladaptive coping,continuous exploration of informal help-seeking behavior,formal help-seeking for crisis-triggered or needs-driven),the psychological experience intertwining struggles and expectations(disappointment at not being taken seriously,helplessness at not being understood,expectation of more understanding and support),barriers to help-seeking(lack of knowledge,difficulties with self-disclosure,lack of trust,negative attitudes encountered when seeking informal help,negative experiences during formal help-seeking).Conclusion Adolescents with mood disorder experienced a long and tortuous journey while seeking help,faced with numerous barriers along the process,and desired to be understood and supported.Healthcare professionals should collaborate with families,schools,and other resources,to improve adolescents'mental health literacy and establish a robust social support system,so as to provide reliable support for adolescents with mood disorder in accessing professional mental health services.

Objective:To study the comprehensive surgical treatment of brucellosis with chest wall cysts as the main manifestation.Methods:Retrospective analysis was made on the general information epidemiological characteristics, clinical manifestations, laboratory examinations, imaging examinations, treatment and outcomes of five patients with brucellosis mainly manifested by chest wall cysts admitted to the 948 Hospital of the People's Liberation Army from July 2019 to June 2022.Results:Among the 5 patients, there were 4 males and 1 female, aged between 23 and 64 years old, with a clear history of contact with cattle and sheep. The main clinical manifestation was painless cystic masses on the chest wall. Both the serum tiger red plate agglutination test (RBPT) and the test tube agglutination test (SAT) were positive. Four cases were infected with Brucella and one case was infected with Actinobacillus pleuropneumoniae (considered as Brucella infection based on the overall condition). All patients exhibited abnormal chest wall signals (manifesting as hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging) on magnetic resonance imaging(MRI), and were ultimately diagnosed with brucellosis presenting predominantly as chest wall cysts. After complete removal of the chest wall cyst through surgery, a combination treatment of rifampicin capsules and doxycycline hyclate tablets was given for 6 weeks. There were no significant adverse reactions and the wound healed in one stage. During the postoperative follow-up period of 11 - 40 months, MRI reexamination demonstrated no evidence of chest wall cyst recurrence, and all SAT results were negative. Conclusions:Patients with brucellosis presenting as chest wall cysts are clinically rare and lack specific symptoms. Surgical resection of the affected lesion combined with early, standardized, combined, and full course antimicrobial therapy results in a good prognosis for the patient.

Objective:To analyze the clinical characteristics of patients with myeloproliferative neoplasms (MPN) complicated with portal hypertension and evaluate the efficacy of ruxolitinib treatment.Methods:A total of 42 patients with MPN complicated with portal hypertension and 84 patients with MPN without portal hypertension who were admitted to the Department of Hematology of the Zhongshan Hospital, Fudan University from January 2018 to December 2023 were retrospectively included. The clinical characteristics of the two groups were compared. The MPN combined with portal hypertension group was divided into the ruxolitinib group ( n=18) and the traditional treatment group ( n=24) according to different treatment methods. The baseline characteristics and therapeutic effects of the two groups were compared. Results:Compared with patients with MPN without portal hypertension, patients with MPN combined with portal hypertension were younger (median age 49 years vs 63 years), and were more common in females [54.76%(23/42) vs 41.67%(35/84)]. The proportion of JAK2V617F mutation was higher [88.09%(37/42) vs 70.23%(59/84)], and the incidence of portal vein thrombosis was higher [57.14%(24/42) vs 1.19%(1/84)]. The incidence of gastrointestinal bleeding was high [45.24%(19/42) vs 4.76%(4/84)], and the hemoglobin and platelet counts were lower (all P<0.05). In terms of MPN classification, the proportions of PrePMF (5/18) and Post-ET-MF (4/18) were relatively high in the ruxolitinib group, while the proportions of essential thrombocythemia (ET) [41.67%(10/24)] and polycythemia vera (PV) [25.00%(6/24)] were relatively high in the traditional treatment group. The distribution of driver genes showed that the JAK2V617F mutation rate in the ruxolitinib group was higher than that in the traditional treatment group (all P<0.05). The proportion of patients with spleen volume reduction ≥35%(SVR35) in the ruxolitinib group was 4/18, and that in the traditional treatment group was 8.33%(2/24), with no statistically significant difference ( P=0.21). The portal vein diameter in the ruxolitinib group decreased compared with the baseline [(14.2±2.1)mm vs (16.5±2.8)mm, P=0.02], while no improvement was observed in the traditional treatment group. Conclusions:Ruxolitinib can effectively improve the portal vein diameter of patients with MPN complicated with portal hypertension.

OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia(VaD)model rats.METHODS VaD rat model was established by bilateral common carotid artery ligation.The experimental animals were randomly divided into sham operation group(SHAM),model group(MOD),Yifei xuanfei jiangzhuo formula low-dose group(YFXF-L),Yifei xuanfei jiangzhuo formula high-dose group(YFXF-H),and Donepezil hydrochloride group(positive control),with 9 animals in each group.After 30 days of intervention,the spatial learning memory ability was assessed by Morris water maze experiment;HE staining was used to observe histopathological changes in CA1 area of hippocampus;ELISA was used to detect the levels of serum inflammatory factors[interleukin-1β(IL-1β)and IL-4];Western blot was used to detect the expressions of heat shock protein 90(HSP90)/mixed lineage kinase domain-like protein(MLKL)/dynamin-related protein 1(Drp1)pathway-related proteins,mitochondrial fusion proteins(MFN1,MFN2),and adenosine triphosphate synthase 5A(ATP5A)in hippocampal tissues.The immunohistochemistry was used to detect the level of phosphorylated MLKL(p-MLKL);real-time fluorescence quantitative PCR was adopted to detect mRNA expressions of HSP90,MFN1,MFN2 and ATP5A.RESULTS Compared with SHAM group,the escape latency of rats in the MOD group was significantly prolonged,the number of crossing the platform was significantly reduced,and the hippocampal tissues showed typical neuronal damage characteristics,the positive expression level of p-MLKL and the serum level of IL-1β significantly increased,while the serum level of IL-4 significantly decreased,the protein and mRNA expression of HSP90,as well as the protein expressions of p-MLKL/MLKL and p-Drp1(Ser616)/Drp1 were all significantly increased in hippocampal tissue,the protein and mRNA expressions of MFN1,MFN2 and ATP5A,and protein expression of p-Drp1(Ser637)/Drp1 were all significantly decreased(P＜0.05).After the intervention of Yifei xuanfei jiangzhuo formula,above indicators in each treatment group were all significantly reversed(P＜0.05).CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway,inhibiting mitochondrial fission,thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

Objective:To analyze the clinical characteristics of patients with myeloproliferative neoplasms (MPN) complicated with portal hypertension and evaluate the efficacy of ruxolitinib treatment.Methods:A total of 42 patients with MPN complicated with portal hypertension and 84 patients with MPN without portal hypertension who were admitted to the Department of Hematology of the Zhongshan Hospital, Fudan University from January 2018 to December 2023 were retrospectively included. The clinical characteristics of the two groups were compared. The MPN combined with portal hypertension group was divided into the ruxolitinib group ( n=18) and the traditional treatment group ( n=24) according to different treatment methods. The baseline characteristics and therapeutic effects of the two groups were compared. Results:Compared with patients with MPN without portal hypertension, patients with MPN combined with portal hypertension were younger (median age 49 years vs 63 years), and were more common in females [54.76%(23/42) vs 41.67%(35/84)]. The proportion of JAK2V617F mutation was higher [88.09%(37/42) vs 70.23%(59/84)], and the incidence of portal vein thrombosis was higher [57.14%(24/42) vs 1.19%(1/84)]. The incidence of gastrointestinal bleeding was high [45.24%(19/42) vs 4.76%(4/84)], and the hemoglobin and platelet counts were lower (all P<0.05). In terms of MPN classification, the proportions of PrePMF (5/18) and Post-ET-MF (4/18) were relatively high in the ruxolitinib group, while the proportions of essential thrombocythemia (ET) [41.67%(10/24)] and polycythemia vera (PV) [25.00%(6/24)] were relatively high in the traditional treatment group. The distribution of driver genes showed that the JAK2V617F mutation rate in the ruxolitinib group was higher than that in the traditional treatment group (all P<0.05). The proportion of patients with spleen volume reduction ≥35%(SVR35) in the ruxolitinib group was 4/18, and that in the traditional treatment group was 8.33%(2/24), with no statistically significant difference ( P=0.21). The portal vein diameter in the ruxolitinib group decreased compared with the baseline [(14.2±2.1)mm vs (16.5±2.8)mm, P=0.02], while no improvement was observed in the traditional treatment group. Conclusions:Ruxolitinib can effectively improve the portal vein diameter of patients with MPN complicated with portal hypertension.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.