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 effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.

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 ofHSP90， 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.

BACKGROUND: Gout is a chronic disease primarily caused by elevated urate levels, severely affecting joint health. Its global distribution varies, and updated data for China are lacking. This study aimed to analyze the current burden and trends of gout globally and in China, examining the burden by gender, age, and risk factors while providing future predictions. METHODS: This descriptive epidemiological secondary analysis utilized data from the Global Burden of Disease, Injuries, and Risk Factors (GBD) 2021 study. Age-standardized incidence rate (ASIR), prevalence rate (ASPR), and disability-adjusted life years (DALYs) rates (ASDR) were used to assess the gout burden. Trends from 1990 to 2021 were analyzed across global regions, genders, and sociodemographic index (SDI) levels. The burden in China was further examined by gender, age, and associated risk factors. The Bayesian age-period-cohort (BAPC) model was used to predict future trends. Gout burden in China and the United States was compared. RESULTS: In 2021, gout affected 57 million people globally, with 9.4 million new cases and 1.75 million DALYs. From 1990 to 2021, the ASIR, ASPR, and ASDR increased by 17.2%, 21.9%, and 21.3%, respectively. Males experienced a significantly higher burden, with greater ASIR, ASPR, and ASDR increasing with higher SDI levels. In China, male ASIR, ASPR, and ASDR were over 2.8 times those of females, and the burden increased with age. In 2021, 31.4% of gout-related DALYs in China were attributed to high body mass index and 7.6% to kidney dysfunction. Between 1990 and 2021, the high body mass index-related burden of gout rose annually for both genders, while the kidney dysfunction-related gout burden remained stable. By 2050, the burden of gout in China is expected to continue increasing, with a slower rise in females and a decline in males after an initial increase. However, the overall burden will remain substantial. In comparison, the gout burden will be higher in the United States than in China. CONCLUSIONS Gout is becoming a significant health burden globally and in China, particularly among Chinese males and older individuals. With the aging population and lifestyle changes exacerbating the issue, effective strategies and measures are essential to prevent or reduce gout-related health issues.
Humans ; Gout/epidemiology* ; Male ; Female ; Incidence ; Middle Aged ; Prevalence ; China/epidemiology* ; Adult ; Risk Factors ; Aged ; Global Burden of Disease ; Disability-Adjusted Life Years ; Young Adult ; Adolescent ; Quality-Adjusted Life Years

Objective:To observe the effects of adipose-derived stem cells(ADSC)combined with acellular scaffold(AS)on the ultrastructure of dorsal root ganglion and the protein and mRNA expression levels of ciliary neurotrophic factor(CNTF),Janus kinase 2(JAK2),phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3)and phosphorylated STAT3(p-STAT3)in the rats with sciatic nerve injury(SNI),and to clarify the protective effect of ADSC combined with AS on dorsal root ganglion in the SNI rats and its possible mechanism.Methods:The rat ADSCs were isolated and cultured and their multidirectional differentiation potential was detected.The AS of rats was prepared,and ADSCs were injected into the AS to construct tissue-engineered nerve.A total of 36 rats were randomly divided into control group,model group,AS group,and ADSC+AS group.The rats in control group were routinely fed,and the rats in other groups were used to establish the SNI models by resecting 10 mm of right sciatic nerve.The rats in model group received no further treatment,while the rats in AS group and ADSC+AS group were bridged with AS and the constructed tissue-engineered nerve at the two ends of the injured nerve,respectively.At 6 weeks after surgery,transmission electron microscope was used to observe the ultrastructure of dorsal root ganglion of the rats in various groups;immunofluorescence method was used to detect the protein expression levels of CNTF,p-JAK2,and p-STAT3 in dorsal root ganglion of the rats;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of CNTF,JAK2,and STAT3 in dorsal root ganglion of the rats in various groups.Results:After 7 d of primary ADSC culture,a large number of large and long spindle-shaped cells were observed under the inverted microscope,arranged in clusters or whirlpools;red lipid droplets were observed with oil red O staining under microscope,and calcified nodules were observed with Alizarin red staining under microscope,indicating that the isolated and cultured cells had multidirectional differentiation ability.Compared with normal nerve tissue,the level of DNA in AS of rats was significantly decreased(P<0.05).Compared with control group,the nuclear membrane of dorsal root ganglion cells in model group was uneven and serrated,the number of organelles in the cytoplasm was decreased,mitochondria were swollen with broken or missing cristae and unclear structure;the CNTF protein and mRNA expression levels were significantly decreased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly increased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly increased(P<0.01).Compared with model group,the serrated change of nuclear membrane of the dorsal root ganglion cells in AS group was significantly alleviated,the number of organelles in the cytoplasm was increased,and mitochondrial swelling was reduced;in ADSC+AS group,the nuclear membrane of dorsal root ganglion cells tended to be intact,the number of organelles was increased,and mitochondrial swelling and vacuolization were significantly reduced;the CNTF protein and mRNA expression levels in the dorsal root ganglion in AS group and ADSC+AS group were significantly increased(P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Compared with AS group,the CNTF protein and mRNA expression levels in ADSC+AS group were significantly increased(P<0.05 or P<0.01),the p-JAK2 and p-STAT3 protein expression levels were significantly decreased(P<0.01),and the JAK2 and STAT3 mRNA expression levels were significantly decreased(P<0.01).Conclusion:The application of ADSC combined with AS can improve the ultrastructure of dorsal root ganglion in the SNI rats,and the mechanism may be related to the increased CNTF expression and decreased activation of the JAK2/STAT3 signaling pathway in the dorsal root ganglion by ADSC combined with AS application.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

The incidence of breast cancer is increasing year by year,and its pathogenesis is highly complex.The dysregulation of gut microbiota function is closely related to the occurrence and development of breast cancer.The estrogen levels through enterohepatic circulation is regulated by β-glucuronidase produced by the gut microbiota,thereby influencing the occurrence and development of hormone receptor-positive breast cancer and leading to tamoxifen resistance.The metabolites from the gut microbiota,such as short-chain fatty acids(SCFAs)and lithocholic acid(LCA),can participate in regulating the tumor cell cycles and cell proliferation.The colonization of gut microbiota maintains the integrity of the intestinal barrier and regulates the anti-tumor immunity mediated by T lymphocytes.Maintaining gut microbiota homeostasis can enhance the efficacy of tumor chemotherapy and immunotherapy and reduce the adverse reactions in anti-tumor treatments.The targeted action of engineered probiotics in immunotherapy can improve the precision of drug treatment.The effect of gut microbiota on radiotherapy is not yet clear,but regulating gut microbiota can aid in the treatment of radiation enteritis.This review discusses the correlation and effect of gut microbiota on breast cancer and analyzes its role in the treatment of breast cancer.

ObjectiveTo explore the characteristics and major factors influencing mental health literacy (MHL) among non-graduating middle school and high school students in Taizhou, Zhejiang Province, and to provide a reference for the promotion of mental health literacy among adolescents. MethodsFrom September to October 2023, a stratified random cluster sampling method was used to conduct a questionnaire survey among students from three classes each in non-graduating grades in four middle schools and four high schools in Taizhou, Zhejiang Province. The survey included basic demographic information, a Structured Mental Health Literacy Questionnaire (MHLQ), and other psychological scales [Educational Stress Scale for Adolescents (ESSA), Perceived Choice Single Scale (PC), Child Depression Inventory (CDI), Generalized Anxiety Disorder (GAD), The University of California at Los Angeles 3-item Loneliness Scale (UCLA-3) and Multidimensional Scale of Perceived Social Support (MSPSS)]. t-tests, chi-square tests, analysis of variance (ANOVA), and multiple linear regressions were applied for the statistical analysis of the data. ResultsThe mental health literacy average score of 2 094 students was (82.3±15.8) points, with a mean of (4.1±0.8) points. The dimension of belief in mental health rights had the highest score. There were significant differences in the mental health literacy score across different dimensions for students with different household registration, economic levels, academic performance, and father’s education level (P<0.001). Multiple linear regression analysis indicated that rural household registration, lower paternal education level, greater academic pressure, a weaker sense of control over one’s behavior, less social support, and symptoms of loneliness, depression, or anxiety were associated with poorer mental health literacy among the students. ConclusionThe mental health literacy of middle school and high school students in Taizhou is generally good, but there are differences among students with different characteristics. Targeted interventions should be carried out for students from rural areas, with poorer mental health, and less low social support to improve the overall mental health literacy of adolescents.

Objective To investigate the status quo of pain catastrophizing(PC)in the patients with di-abetic peripheral neuropathic pain(DPNP),and to analyze the influencing factors to provide reference for for-mulating clinical preventive intervention strategies.Methods A total of 206 patients with DPNP admitted and treated in the People's Hospital of Guangxi Zhuang Autonomous Region were selected as the research sub-jects by convenience sampling method.The general data questionnaire,Numerical Rating Scale(NRS),Pain Catastrophizing scale(PCS),Perceived Social Support Scale(PSSS)and diabetes distress scale(DDS)were used to conduct the investigation.Results The incidence rate of PC in 206 cases of DPNP patients was 44.66％(92/206),and the total score of PCS was(30.10±5.16)points.The results of multiple linear regres-sion analysis showed that the gender,duration of diabetes(≥10 years),multiple drug use,number of compli-cations(＞5),NRS score,PSSS score and scores of DDS dimensions were the main influencing factors of PC(all P＜0.05),which could explain 92.3％of the total variation of PC.Conclusion The PC incidence rate in the patients with DPNP is high.Clinical healthcare workers should pay attention to the evaluation of PC in these patients,and formulate the scientific and effective targeted intervention measures according to the main influen-cing factors to help the patients to reduce the pain burden in order to reduce the level of PC.

Objective:To understand and compare the clinical characteristics of children and adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant BA.5 and BA.2 subtypes in Shanghai City.Methods:The clinical data of 524 children hospitalized with coronavirus disease 2019(COVID-19) at the Children′s Hospital of Fudan University during the period of BA.5 predominance from December 1, 2022 to January 20, 2023 were collected, which included age, gender, clinical symptoms and laboratory examination results. And the clinical data of household close contacts were also collected. The clinical data of children and their household contacts infected with Omicron BA.2 subtypes during the period of BA.2 predominance from April 4 to April 30, 2022 were collected and compared.The clinical characteristic of critical and non-critical cases, child and adult cases during the period of BA.5 predominance were compared.Statistical analyses were conducted using independent samples t-test, Mann-Whitney U test, chi-square test or Fisher′s exact test. Results:The age of 524 hospitalized children was five days to 16 years old. Among them, 301(57.4%) were male and 223(42.6%) were female. Additionally, there were 29 critical cases (5.5%) and 495 non-critical cases (94.5%). Critical cases had significantly higher fever peak, more shortness of breath occurrence, more pneumonia and underlying diseases compared to non-critical cases, with statistically significant differences ( t=12.06, χ2=34.90, 10.04 and 31.10, respectively, all P<0.05). Regarding laboratory examinations, critical cases exhibited significantly higher frequencies of decreased lymphocyte count, elevated levels of C-reactive protein, procalcitonin and interleukin-6, abnormal liver function and kidney function, and abnormal creatine kinase isoenzyme compared to non-critical cases, with statistically significant differences ( χ2=8.18, Z=-4.61, Z=-4.28, Z=-5.13, χ2 =195.90, Fisher′s exact test and χ2=136.13, respectively, all P<0.05). Non-critical children cases infected with Omicron variant BA.5 subtype exhibited a higher proportion of symptomatic infections compared to adults. Among children, the occurrence rates of fever and gastrointestinal symptoms (nausea, vomiting, diarrhea) were higher, whereas among adults, the occurrence rate of cough was higher. The differences were statistically significant ( χ2=11.16, 11.83, 8.50 and 28.14, respectively, all P<0.05).From December 1, 2022 to January 20, 2023, a total of 588 children cases and 791 adult cases were collected, while from April 4 to April 30, 2022, a total of 355 children cases and 755 adult cases were collected.In the children group, the occurrence rates of cough, convulsions and critical cases were higher in BA.5 subtype-infected children compared to those infected with the BA.2 subtype, with statistically significant differences ( χ2=37.95, 40.78 and 15.54, respectively, all P<0.001).In the adult group, BA.5 subtype-infected individuals had higher fever peak, longer duration of fever, and higher occurrence of fever, cough and gastrointestinal symptoms, compared to those infected with the BA.2 subtype.The differences were statistically significant ( t=-4.40, Z=-9.64, χ2=47.29, 124.09 and 29.90, respectively, all P<0.001). Conclusions:During the peak periods of BA.5 subtype of the Omicron variant in Shanghai City, critical cases have severe systemic symptoms and a higher prevalence of underlying diseases compared to non-critical cases. Among non-critical cases infected with BA.5 subtype, the proportion of symptomatic infections in children is higher than adults, with fever and gastrointestinal symptoms more common than adults, while cough symptoms are more common seen in adults.The occurrence rate of convulsions and critical cases is higher in children infected with variant BA.5 subtype compared to those infected with BA.2 subtype.The systemic symptoms are more severe in adults infected with BA.5 subtype compared to those infected with BA.2 subtype.