In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months.Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine.The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers(AIM)based on polychromatic flow cytometry.Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine,more than 90%of adults had detectable Spike and Non-spike antigen-specific CD4+ T cells immune responses(Spike:14/15,P=0.0001;Non-spike:15/15,P<0.0001).80%of adults had detectable Spike and Non-spike antigen-specific CD8+ T cells immune responses(Spike:12/15,P=0.0463;Non-spike:12/15,P=0.0806).Antigen-specific CD4+ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory(CM)and effector memory 1(EM1)cells.On the other hand,in terms of helper subsets,antigen-specific CD4+ T cells mainly showed T helper 1/17(Th1/17)and T helper 2(Th2)phenotypes.Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4+ T cell memory responses,which may be the key factor for the low proportion of severe coronavirus disease 2019(COVID-19)infection in China.

Objective:To investigate effect of acacetin on alveolar epithelial cell damage caused by Streptococcus pneumoniae(SP)infection by regulating sirtuin 1(Sirt1)-mediated 5'-AMP activated protein kinase(AMPK)/nuclear factor erythroid-2 related factor 2(Nrf2)signaling pathway.Methods:Alveolar epithelial cells A549 cultured in vitro were infected with SP to establish a cell damage model.After treatment with acacetin at final concentrations of 0,5,25,50,100,150,200 μmol/L,CCK-8 was performed to detect cell viability of each treatment group and optimal concentration of acacetin was screened.A549 cells cultured in vitro were ran-domly separated into five groups:control group,model group,acacetin(150 μmol/L)group,EX527(Sirt1 inhibitor,40 μmol/L)group,acacetin(150 μmol/L)+EX527(40 μmol/L)group,control group was not treated,other groups were infected with SP to establish a cell damage model,and then treated with 150 μmol/L acacetin and 40 μmol/L EX527,CCK-8 and flow cytometry were performed to measure cell viability and apoptosis rate in each group;kits were performed to measure levels of reactive oxygen species(ROS),superoxide dismutase(SOD),malondialdehyde(MDA),lactate dehydrogenase(LDH)and IL-10,IL-1β,TNF-α levels of cells in each group;Western blot was performed to measure proliferation-related proteins Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-related proteins caspase-9,Bax,Sirt1 and AMPK/Nrf2 signaling pathway proteins p-AMPK/AMPK,Nrf2 expres-sions of cells in each group.Results:Model group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels than control group(P<0.05).Compared with model group and acacetin+EX527 group,acacetin group had increased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and decreased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05);EX527 group had decreased A549 cell viability,SOD and IL-10 levels,p-AMPK/AMPK,Sirt1,Nrf2,Ki-67 and PCNA protein expressions(P<0.05),and increased apoptosis rate,MDA,LDH,ROS,IL-1β and TNF-α levels(P<0.05).Conclusion:Acnestin can activate AMPK/Nrf2 signaling by up-regulating Sirt1 expression,thereby promoting secretion of anti-inflammatory factors,reducing production of ROS and pro-inflammatory factors,reducing inflammation and oxidative stress,and finally alleviating neuronal damage.

Objective:To analyze the growth characteristics of different genotypes of Japanese encephalitis virus (JEV) in different cell lines, and to provide scientific basis for the selection of cell lines in the study of JEV.Methods:BHK-21, Vero, C6/36, PK-15, DF-1, N2a, SH-sy5y and MDCK cell lines were selected. The proliferation ability of genotype 1 (NX1889 strain), genotype 3 (P3 strain) and genotype 5 (XZ0934 strain) JEV in these cell lines was evaluated by plaque assay and RT-qPCR.Results:Significant cytopathogenic effects (CPE) were observed in BHK-21, Vero, C6/36, DF-1, N2a and PK-15 cell lines across all three JEV genotypes. However, no significant differences in CPE characteristics were observed within the same cell line. SH-sy5y and MDCK cell lines did not show significant CPE, but virus proliferation was detected in SH-sy5y cell line, while MDCK cell line were found to be insensitive to JEV. No significant difference was observed in the proliferation curves of G1, G3 and G5 JEV in BHK-21, Vero and SH-sy5y cell lines. In C6/36 and PK-15 cell lines, the titer of G1 JEV was higher than that of G3 and G5. In DF-1 cell line, G5 demonstrated a higher titer than the other two genotypes, whereas in N2a cell line, G5 showed a lower titer than the other two.Conclusions:There are differences in the proliferation of three different genotypes of JEV in different cell lines, which can provide reference for the study of JEV in different directions.

Objective:To explore the association between occupational noise perception and cardiovascular disease (CVD), depression symptoms, as well as their comorbidity in occupational population and provide evidence for the prevention and control of physical and mental illnesses.Methods:A cross-sectional survey design was adopted, based on baseline data in population in 28 prefectures in Sichuan Province and Guizhou Province, and 33 districts (counties) in Chongqing municipality from Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during October to December 2021. A questionnaire survey was conducted to collect information about noise perception, depressive symptoms, and the history of CVD. Latent profile analysis model was used to determine identify noise perception type, and multinomial logistic regression analysis was conducted to explore the relationship between different occupational noise perception types and CVD, depression symptoms and their comorbidity.Results:A total of 30 509 participants were included, the mean age was (36.6±10.5) years, and men accounted for 82.0%. The direct perception of occupational noise, psychological effects and hearing/sleep impact of occupational noise increased the risk for CVD, depressive symptoms, and their comorbidity. By using latent profile analysis, occupational noise perception was classified into four levels: low, medium, high, and very high. As the level of noise perception increased, the association with CVD, depressive symptoms, and their comorbidity increased. In fact, very high level occupational noise perception were found to increase the risk for CVD, depressive symptoms, and their comorbidity by 2.14 (95% CI: 1.73-2.65) times, 8.80 (95% CI: 7.91-9.78) times, and 17.02 (95% CI: 12.78-22.66) times respectively compared with low-level occupational noise perception. Conclusions:Different types of occupational noise perception are associated with CVD and depression symptom, especially in the form of CVD complicated with depression symptom. Furthermore, the intensity of occupational noise in the work environment should be reduced to lower the risk for physical and mental health.

Objective:To investigate the association between alcohol consumption and hypertension and SBP, DBP and the mediating effects of body mass index (BMI) and lipid level in occupational population, and provide reference for the intervention and prevention of hypertension.Methods:Based on the data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., the information about the demographic characteristics, behavior and lifestyle, blood pressure and lipids level of the participants were collected through questionnaire survey, physical examination and blood biochemical test. Logistic/linear regression was used to analyze the association between alcohol consumption and hypertension, SBP and DBP. The individual and joint mediating effects of BMI, HDL-C, LDL-C, TG, and TC were explored through causal mediating analysis. A network analysis was used to explore the correlation between alcohol consumption, BMI and lipid levels, and hypertension.Results:A total of 22 887 participants were included, in whom 1 825 had newly detected hypertension. Logistic regression analysis found that current/former drinkers had a 33% increase of risk for hypertension compared with never-drinkers ( OR=1.33, 95% CI:1.19-1.48). Similarly, alcohol consumption could increase SBP ( β=1.05, 95% CI:0.69-1.40) and DBP ( β=1.10, 95% CI:0.83-1.38). Overall, BMI and lipid levels could mediate the associations between alcohol consumption and hypertension, SBP and DBP by 21.91%, 28.40% and 22.64%, respectively. BMI and TG were the main mediators, and they were also the two nodes with the highest edge weight and bridge strength centrality in the network of alcohol consumption, BMI, lipid levels and hypertension. Conclusions:Alcohol consumption was associated with increased risk for hypertension, and BMI and TG were important mediators and key nodes in the network. It is suggested that paying attention to the alcohol consumption, BMI and TG might help prevent hypertension in occupational population.

Objective:To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity.Methods:Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling.Results:Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation.Conclusions:AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone