Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Parkinson's disease （PD） is a complex neurodegenerative disease involving multiple systems and neurotransmitters. Due to the high clinical heterogeneity of PD，it is urgent to establish a comprehensive and long-term traditional Chinese medicine （TCM） management model. In this paper，the conceptual framework of full-cycle management of PD is preliminarily constructed：based on the evolution of the pathophysiological mechanisms of protein deposition and neurotransmitter disorder in PD，the three-stage syndrome characteristics of the prodromal stage （predominant healthy Qi with subtle pathogenic factors），the early clinical stage （declining healthy Qi with growing pathogenic factors） and the middle and late stages （overwhelming pathogenic factors with deficient healthy Qi） are longitudinally described. Through the syndrome differentiation of visceral manifestations，the etiology and pathogenesis of PD motor and non-motor symptoms were comprehensively analyzed，while the matching treatment methods and prescriptions were inferred，and the modular scheme of the combining main symptoms，accompanying symptoms and secondary symptoms was proposed. The conceptual gap of TCM regarding motor complications （'variable syndrome'） and PD-related hyperpyrexia syndrome （'critical syndrome'） was explained. This framework reflects the characteristics of combination of disease and syndrome and overall constant motion，and provides new theories and research ideas for individualized and whole-process management of PD in TCM.

Objective:To discuss the effects of microRNA(miR)-199a-5p overexpression on cell migration and apoptosis in the glioblastoma U251 cells,and to clarify the targeting regulatory relationship between miR-199a-5p and caveolin-1(CAV-1).Methods:The glioblastoma U251 cells and oligodendroglioma Hs683 cells were cultured in vitro.Western blotting method was used to detect the expression levels of CAV-1 protein in 2 kinds of cells;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of miR-199a-5p in 2 kinds of cells.The U251 cells were divided into blank group(non-transfection),mimics NC group(transfected with empty vector),and miR-199a-5p mimics group(transfected with miR-199a-5p mimics).The Hs683 cells were divided into blank group(no transfection),inhibitor NC group(transfected with empty vector),and miR-199a-5p inhibitor group(transfected with miR-199a-5p inhibitor).RT-qPCR method was used to detect the transfection efficiency of the cells in various groups;Western blotting method was used to detect the expression levels of CAV-1 protein in the cells in various groups.TargetScan database was used to predict the binding sites between miR-199a-5p and CAV-1 in the 3'untrans lated region(3'UTR);psiCHECKTM-2-CAV-1-WT and psiCHECKTM-2-CAV-1-Mut were co-transfected with miR-199a-5p mimics and mimics NC into the U251 cells,respectively,forming psiCHECKTM-2-CAV-1-WT+mimics NC group,psiCHECKTM-2-CAV-1-WT+miR-199a-5p mimics group,psiCHECKTM-2-CAV-1-Mut+mimics NC group,and psiCHECKTM-2-CAV1-Mut+miR-199a-5p mimics group;dual-luciferase reporter gene assay was used to verify the targeting relationship between miR-199a-5p and CAV-1;cell scratch assay was used to detect the scratch healing rates of the U251 cells in various groups;flow cytometry was used to detect the apoptotic rates of the U251 cells in various groups.Results:The Western blotting and RT-qPCR results showed that compared with Hs683 cells,the expression level of CAV-1 protein in the U251 cells was significantly decreased(P<0.05);compared with U251 cells,the expression level of miR-199a-5p in the Hs683 cells was significantly increased(P<0.01).Compared with blank group and mimics NC group,the expression level of miR-199a-5p in the U251 cells in miR-199a-5p mimics group was significantly increased(P<0.01),the expression level of CAV-1 protein in the U251 cells in miR-199a-5p mimics group was significantly decreased(P<0.05).Compared with blank group,the expression levels of miR-199a-5p in the Hs683 cells in inhibitor NC group and miR-199a-5p inhibitor group were significantly decreased(P<0.01).No significant differences were observed in the expression levels of CAV-1 protein in the Hs683 cells among various groups(P>0.05).The dual-luciferase reporter gene assay results showed that psiCHECKTM-2-CAV-1-wild type(WT)and psiCHECKTM-2-CAV-1-mutant(Mut)expression vectors were successfully constructed;compared with psiCHECKTM-2-CAV-1-WT-mimics NC group,the relative luciferase activity of WT CAV-1 in the U251 cells in psiCHECKTM-2-CAV-1-WT-miR-199a-5p mimics group was significantly decreased(P<0.01).The cell scratch assay results showed that at 12,24,and 48 h after transfection,compared with blank group,the scratch healing rate of the U251 cells in miR-199a-5p mimics group was significantly decreased(P<0.05 or P<0.01).The flow cytometry results showed that compared with blank group and mimics NC group,the apoptotic rate of the U251 cells in miR-199a-5p mimics group was significantly increased(P<0.01).Conclusion:Transfection of mature miR-199a-5p mimics into the glioblastoma U251 cells can reduce the expression of CAV-1 protein,inhibit glioma cell migration,promote apoptosis,and suppress tumorigenesis and development.The targeting relationship between miR-199a-5p and CAV-1 may represent a potential mechanism for glioma development and could serve as a potential diagnostic and therapeutic target for glioma.

BACKGROUND:Asperosaponin Ⅵ has good osteogenic effects,but its ability to promote cellular osteogenesis under hypoxia environment is not yet clear.OBJECTIVE:To investigate the effect and potential mechanism of Asperosaponin Ⅵ on osteogenic differentiation of MC3T3-E1 cells under hypoxia environment.METHODS:MC3T3-E1 cells were divided into three groups.Cells in the control group were cultured in a complete medium under normoxic conditions(volume fraction of 21％O2);cells in the hypoxia group were cultured in the complete medium under hypoxia conditions(volume fraction of 0.5％O2);and cells in the Asperosaponin Ⅵ group were cultured in the complete medium containing Asperosaponin Ⅵ under hypoxia conditions(volume fraction of 0.5％oxygen).After 24 hours of culture,cell counting kit-8 method and EdU staining were used to detect cell proliferation activity,TUNEL staining and western blot assay were performed to detect cell apoptosis,and flow cytometry was used to detect intracellular reactive oxygen species levels and cell cycle distribution.Each group of cells was cultured in an osteogenic induction medium containing 1×10-5,1×10-6,and 1×10-7 mol/L Asperosaponin Ⅵ under hypoxia conditions for 7 days.The optimal concentration of Asperosaponin Ⅵ for intervention was identified using alkaline phosphatase staining under optical microscopy.Western blot was used to detect the expression of bone morphogenetic protein 2,osteopontin,and PI3K/AKT signaling axis-related proteins.RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation ability of MC3T3-E1 cells decreased under hypoxia conditions.1×10-6 mol/L Asperosaponin Ⅵ could significantly improve the cell proliferation ability under hypoxia conditions and reduce cell apoptosis.(2)Compared with the hypoxia group,the Asperosaponin Ⅵ group showed a decrease in intracellular reactive oxygen species and a significant increase in the proportion of cells in the S phase.(3)Compared with the hypoxia group,the cell morphology in the 1×10-6 mol/L Asperosaponin Ⅵ group was elongated,with more protrusions and darker alkaline phosphatase staining.(4)Compared with the hypoxia group,the expression of bone morphogenetic protein 2 and osteopontin increased in the Asperosaponin Ⅵ group,while the expression of p-PI3K and p-AKT proteins decreased.These findings indicate that under hypoxia conditions,Asperosaponin Ⅵcan promote osteogenic differentiation of MC3T3-E1 cells,possibly by regulating the PI3K/AKT pathway.

BACKGROUND:Asperosaponin Ⅵ has good osteogenic effects,but its ability to promote cellular osteogenesis under hypoxia environment is not yet clear.OBJECTIVE:To investigate the effect and potential mechanism of Asperosaponin Ⅵ on osteogenic differentiation of MC3T3-E1 cells under hypoxia environment.METHODS:MC3T3-E1 cells were divided into three groups.Cells in the control group were cultured in a complete medium under normoxic conditions(volume fraction of 21％O2);cells in the hypoxia group were cultured in the complete medium under hypoxia conditions(volume fraction of 0.5％O2);and cells in the Asperosaponin Ⅵ group were cultured in the complete medium containing Asperosaponin Ⅵ under hypoxia conditions(volume fraction of 0.5％oxygen).After 24 hours of culture,cell counting kit-8 method and EdU staining were used to detect cell proliferation activity,TUNEL staining and western blot assay were performed to detect cell apoptosis,and flow cytometry was used to detect intracellular reactive oxygen species levels and cell cycle distribution.Each group of cells was cultured in an osteogenic induction medium containing 1×10-5,1×10-6,and 1×10-7 mol/L Asperosaponin Ⅵ under hypoxia conditions for 7 days.The optimal concentration of Asperosaponin Ⅵ for intervention was identified using alkaline phosphatase staining under optical microscopy.Western blot was used to detect the expression of bone morphogenetic protein 2,osteopontin,and PI3K/AKT signaling axis-related proteins.RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation ability of MC3T3-E1 cells decreased under hypoxia conditions.1×10-6 mol/L Asperosaponin Ⅵ could significantly improve the cell proliferation ability under hypoxia conditions and reduce cell apoptosis.(2)Compared with the hypoxia group,the Asperosaponin Ⅵ group showed a decrease in intracellular reactive oxygen species and a significant increase in the proportion of cells in the S phase.(3)Compared with the hypoxia group,the cell morphology in the 1×10-6 mol/L Asperosaponin Ⅵ group was elongated,with more protrusions and darker alkaline phosphatase staining.(4)Compared with the hypoxia group,the expression of bone morphogenetic protein 2 and osteopontin increased in the Asperosaponin Ⅵ group,while the expression of p-PI3K and p-AKT proteins decreased.These findings indicate that under hypoxia conditions,Asperosaponin Ⅵcan promote osteogenic differentiation of MC3T3-E1 cells,possibly by regulating the PI3K/AKT pathway.

The emergence of high virulent mutant strains of infectious bursal disease virus(IBDV)becomes a serious threat to the poultry industry.However,the live attenuated IBDV vaccine can potentially revert to a virulent strain.Therefore,it is a necessary to develop safe and effective IB-DV-associated vaccines.The construction of a recombinant Marek's disease(MD)vaccine strain,CVI988,expressing the IBDV VP2 protein,can protect against disease induced by both IBDV and Marek's disease virus(MDV).Here,the IBDV-VP2 gene was integrated into the UL55 locus of CVI988 by bacterial artificial chromosome(BAC)technique,resulting in the recombinant virus CVI988 BAC-VP2.The recombinant virus was characterized by PCR,IFA and subsequently the bi-ological properties of the recombinant virus were investigated.The results showed that the recom-binant virus CVI988 BAC-VP2 was successfully rescued.The VP2 protein stably expressed in chick-en embryo fibroblasts(CEF).The growth kinetics and plague size assays showed that there was comparable replication ability between recombinant virus and parental virus.This study provides the basis for the development of a low-cost vaccine against both IBDV and MDV infections.

Objective:To understand the relationship between unhealthy lifestyle and hyperuricemia, as well as the modification effects of hypertension and dyslipidemia in occupational population and provide a theoretical basis for the prevention of hyperuricemia.Methods:A cross-sectional survey design was adopted, based on baseline data from the Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., which included the population in 28 prefectures from Sichuan Province and Guizhou Province, and 33 districts (counties) from Chongqing Municipality between October and December 2021. This study collected the information about the demographics characteristics, lifestyles, and prevalence of chronic non-communicable diseases of the study subjects through questionnaire, physical measurement and laboratory biochemical test. The unhealthy lifestyle score was scored based on smoking, alcohol consumption, dietary patterns, physical activity, and low weight or overweight, with higher scores being associated with more unhealthy lifestyles. The multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle score, smoking, alcohol consumption, other factors and hyperuricemia, and the stratified analysis was used to explore the modification effect of hypertension and other diseases on the relationship between unhealthy lifestyle and hyperuricemia.Results:A total of 11 748 participants were included in this study, the prevalence of hyperuricemia was 34.4%. Multivariate logistic regression model showed that current/previous smoking, current/previous alcohol consumption and BMI abnormality were risk factors for hyperuricemia, and the unhealthy lifestyle score showed a "cumulative" effect on the risk for hyperuricemia, with higher score increasing the risk of hyperuricemia, and the OR increased from 1.64 (95% CI: 1.34-2.00) to 2.89 (95% CI: 2.39-3.50). Stratified analysis showed that unhealthy lifestyles had a greater impact on the risk for hyperuricemia in people with hypertension and dyslipidemia. Conclusions:The coexistence of multiple unhealthy lifestyles might increase the risk of hyperuricemia, and this effect was stronger in participants with hypertension and dyslipidemia. Timely correction of unhealthy lifestyles, and control of hypertension and dyslipidemia might reduce the risk for hyperuricemia.

Background Non-suicidal self-injury(NSSI)behavior has become a major public health concern and can have significant implications for the physical and mental health of adolescents.Peer victimization is a risk factor for adolesents to have NSSI behavior,so exploring the relationship and underlying mechanism between peer victimization and NSSI functions will provide a promising strategy for the prevention and intervention of NSSI behavior.Objective To investigate the relationship between peer victimization and NSSI functions in adolescents with unipolar and bipolar depression,so as to provide references for the intervention of NSSI behavior in adolescent patients with unipolar and bipolar depression.Methods Using multi-stage stratified sampling,940 adolescents with unipolar and bipolar depression who met the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria for bipolar depressive episodes or depressive disorders were selected from 14 psychiatric hospitals in China.All participations were assessed using Chinese version of the Functional Assessment of Self-Mutilation(C-FASM),Multidimensional Peer-Victimization Scale(MPVS),UCLA Loneliness Scale(UCLA-LS)and Patient Health Questionnaire-9 item(PHQ-9).Pearson correlation coefficient was to assess the correlation among above scales,and the model fit and path coefficients for mediation were analyzed with model 4 in Process 4.0 for SPSS.Results A total of 698(74.26%)adolescents with unipolar and bipolar depression completed the questionnaire survey.NSSI behavior was detected in 374 patients(53.58%).Among adolescents with unipolar and bipolar depression and NSSI behavior,MPVS total score was positively correlated with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.104,0.130,0.266,P<0.05 or 0.01),UCLA-LS score also yielded a positive correlation with the scores of NSSI emotion regulation function,attention-seeking function and social avoidance function in C-FASM(r=0.321,0.112,0.246,P<0.05 or 0.01),and UCLA-LS score was positively correlated with MPVS total score(r=0.241,P<0.01).Loneliness demonstrated a complete mediating role in the relationship between peer victimization and emotion regulation function,with an indirect effect value of 0.033(95%CI:0.019～0.050)and an effect size of 73.33%.A partial mediating effect of loneliness was also observed for the relationship between peer victimization and social avoidance function,with an indirect effect value of 0.016(95%CI:0.007～0.025)and an effect size of 17.98%.Conclusion Loneliness may act as a mediator in the relationship between the peer victimization and the NISS emotion regulation and social avoidance functions in adolescents with unipolar and bipolar depression and NSSI behaviors.

Objective To evaluate the diagnostic efficacy of pelvic floor ultrasound parameters in post-cesarean stress urinary incontinence (SUI) and biofeedback efficacy evaluation. Methods A total of 215 pregnant women who underwent cesarean section were selected by simple sampling method. According to whether postpartum SUI occurred, they were divided into SUI group (n=88) and non-SUI group (n=127). The SUI group received biofeedback therapy. The ultrasonic parameters of pelvic floor were compared between the two groups. The ultrasound parameters of pelvic floor in the SUI group were compared before and after treatment. Results Bladder neck descent (BND), urethral rotation angle (URA) as well as levator hiatal area (LHA) and posterior urethrovesical angle (PUVA) in Valsalva state of the SUI group were significantly higher than those in the non-SUI group (P < 0.05). After biofeedback therapy, the total effective rate of 88 patients with SUI after cesarean section was 94.32%. The BND, URA as well as LHA and PUVA in Valsalva state of the SUI group after treatment were significantly lower than those before treatment (P < 0.05). The area under the curve (AUC) of BND, URA, LHA and PUVA in predicting the effect of biofeedback on post-cesarean section SUI were 0.853, 0.897, 0.865 and 0.887, respectively. Conclusion Pelvic floor ultrasound parameters are highly effective in diagnosing SUI after cesarean section and evaluating the effect of biofeedback therapy.

Objective: To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. Methods: A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. Results: After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible. Conclusion Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.