ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation， migration， and aerobic glycolysis of hepatocellular carcinoma （HCC） using cell experiments， as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected， and Sprague-Dawley rats were randomly divided into blank serum group， inhibitor group， and high-， middle-， and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells； glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells； RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression， related proteins， and phosphorylation of the protein kinase B （AKT）/mammalian target of rapamycin （mTOR） signaling pathway. A one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group， the Biejia Decoction Pill groups had significant reductions in OD value， migration rate during different periods of time， glycolytic rate-limiting enzymes （hexokinase， phosphofructokinase， pyruvate kinase）， and glycolytic metabolites （pyruvate， lactic acid， ATP） （all P<0.05）. RT-qPCR results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR， and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT （all P<0.05）. Western blot results showed that compared with the blank serum group， the high-， middle-， and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins， and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins （all P<0.05）. ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells， thereby inhibiting their proliferation and migration， possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.

Objective To explore the nephrotoxic effects of exposure to perfluorobutanoic acid (PFBA) and its mechanism in mice, with a particular focus on analyzing the changes in kidney metabolism and their potential implications. Methods The specific pathogen free C57BL/6 mice were randomly divided into control group, low-dose group, and high-dose group, with 10 mice in each group. Mice in the three groups received intragastric administration of PFBA solution at doses of 0, 35 and 350 mg/kg body weight, once per day for seven consecutive days. The histopathological changes of kidneys of mice in these three groups were evaluated. Metabolomic profiling of mouse kidneys was performed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differentially accumulated metabolites (DAMs) were identified based on the Human Metabolome Database, and related metabolic pathways were analyzed through MetaboAnalyst 6.0 and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Histopathological analysis of kidneys showed that the renal pelvis mucosa of mice in the low-dose group presented focal mild inflammatory changes without marked structural damage, whereas mice in the high-dose group showed severe inflammation and partial destruction of renal structure. The kidney coefficient of mice in both low-dose group and the high-dose group decreased (both P<0.05), and the Paller scores of renal tissues increased (both P<0.05) compared with that in the control group. The Paller score of mouse renal tissue in the high-dose group was higher than that in the low-dose group (P<0.05). Metabolomic profiling identified 46 DAMs (26 upregulated, 20 downregulated) in the low-dose group and 104 DAMs (54 upregulated, 50 downregulated) in the high-dose group, with 26 shared DAMs between the two dose groups. KEGG pathway analysis revealed that DAMs were mainly involved in metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid and steroid hormone synthesis. Conclusion Acute exposure to PFBA can cause kidney injury in mice. Lipid metabolism pathways such as glycerophospholipid and sphingolipid metabolism is involved in the development of acute renal toxicity of PFBA.

Objective To investigate the protective effects of Kaempferol(KAE)against hepatic lipid de-position induced by a high-fat diet,as well as the underlying mechanisms.Methods C57BL/6J male mice were fed a high-fat diet for 22 weeks to establish a chronic nonalcoholic steatohepatitis(NASH)model.KAE was admin-istered during the last 8 weeks as an interventional agent to evaluate its effects.Liver lipid deposition was assessed,and the expression levels of endoplasmic reticulum(ER)stress-related proteins,activation of the Farnesoid X Re-ceptor(FXR)signaling pathway,and the expression of lipid synthesis-related genes were analyzed.In vitro,pal-mitic acid(PA)was used to stimulate AML-12 cells to induce lipid accumulation.Additionally,siRNA targeting FXR was transfected into AML-12 cells to investigate the role of the ER stress-FXR signaling pathway in mediating the effects of KAE.Results The intervention of kaempferol inhibited the rapid weight gain induced by a high-fat diet,reduced serum total cholesterol,triglyceride levels,and ALT activity,effectively alleviated large-scale lipid aggregation in the liver,thereby exerting a protective effect against hepatic lipid deposition in NASH.Mechanisti-cally,KAE decreased hepatic ER stress,promoted the expression of FXR and its activation marker SHP,thereby suppressing the expression of FASN and reducing hepatic lipid synthesis.In vitro,KAE treatment significantly re-versed the inhibitory effect of excessive ER stress on FXR activity,as evidenced by the upregulation of FXR activ-ity leading to decreased FASN expression and reduced steatosis in AML-12 cells.Moreover,FXR knockdown mark-edly abolished the protective effects of KAE on lipid deposition in AML-12 cells exposed to PA,by eliminating the promoting effect of KAE on SHP expression and the SHP-mediated suppression of SREBP1c.Conclusions KAE treatment alleviated ER stress,thereby enhancing FXR/SHP signaling and subsequently suppressing lipid synthesis to reduce hepatic lipid accumulation.These findings suggest that KAE holds therapeutic potential for the manage-ment of hepatic steatosis in NASH.

Objective Based on the three tools of the AGREE Next Steps Consortium(AGREE Ⅱ),China Clinical Guidelines Evaluation System(AGREE-China)and Scientificity Transparency Applicability Rankings(STAR),the methodological quality of Chinese medicine clinical treatment guidelines for coronary heart disease published by domestic institutions was systematically evaluated.Methods Computer system retrieval of China National Knowledge Infrastructure(CNKI),WanFang Data,Chinese Science and Technology Journal Database(VIP),China Biology Medicine(CBM)and Yimai Tong,and collect clinical practice guidelines of traditional Chinese medicine for coronary heart disease issued by domestic institutions(including expert consensus).The search period was from the establishment of the database to December 31,2023.Results A total of 21 guidelines were included.AGREE Ⅱ recommended 13 for grade A and 8 for grade B.The approval-China review strongly recommends 12,weakly recommends 8,and does not recommend 1.The highest STAR rating is a 4.0 star recommendation and the lowest is a 1.5 star recommendation.Conclusions There are a large number of TCM diagnosis and treatment guidelines and expert consensus on coronary heart disease in China,but the quality is uneven.It is suggested that the future guideline formulation should pay attention to the evidence-based principle,promote the standardization and standardization of the guideline formulation,and improve the scientific and applicability of the guideline.

Objective:To analyze the effect of precipitation on road traffic injuries (RTI) in Zhejiang Province.Methods:The RTI surveillance and meteorological data from 2009 to 2022 in Zhejiang Province were collected. Based on the time-stratified case-crossover design, the precipitation of case day and control day was compared, and the distributed lag nonlinear model was applied to analyze the correlation of precipitation and RTI. Stratified analyses were conducted to analyze the effect modification of gender, age, injury location, and temperature. An attributable fraction was used to assess the burden of RTI caused by precipitation.Results:A total of 239 970 RTIs were monitored in Zhejiang Province from 2009 to 2022, averaging 46 daily cases. The distributed lag nonlinear model showed that compared with no rain, the risk of RTI increased first and then decreased with the increase of precipitation. The risk of RTI was the highest when the precipitation was 30.99 mm ( OR=1.08, 95% CI: 1.05-1.11). The adverse effects on RTI mainly occurred on the day of precipitation, and it showed insignificant or protective effects with the extension of lag days. 1.34%(95% CI: 1.31%-1.36%) of RTI could be attributed to precipitation. Stratified analysis showed that gender, age, injury location, and temperature may modify the effect of precipitation on RTI. Precipitation caused a heavier burden on RTI in subgroups aged 18-64, females, and occurring on roads and in low temperatures. Conclusions:Precipitation can increase the risk of RTI. People aged 18-64 or females are the key groups for RTI prevention, and prevention and control efforts of precipitation-related RTI should be increased in road and low-temperature environments.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective:To investigate the correlation of systemic immune inflammatory index (SII) and monocyte-to-lymphocyte ratio (MLR) with chronic kidney disease-mineral and bone disorder (CKD-MBD) in patients with stage 5 chronic kidney disease (CKD).Methods:A cross-sectional survey method was used to select 152 patients with stage 5 CKD who received treatment in the Department of Nephrology, Hefei First People's Hospital from January 2023 to January 2024 as research subjects. Based on the patients' intact parathyroid hormone (iPTH) levels, they were divided into three groups: low iPTH group ( n = 63), normal iPTH group ( n = 46), and high iPTH group ( n = 43). The differences in SII and MLR among the three groups were analyzed. The relationship between SII and the occurrence of high iPTH was analyzed to assess the predictive efficacy of SII for high iPTH. Results:Among the 152 patients with stage 5 CKD, the low iPTH group accounted for 41.45% (63/152), the normal iPTH group for 30.26% (46/152), and the high iPTH group for 28.29% (43/152). The prevalence of hypertension in each group was as follows: 85.71% (54/63) in the low iPTH group, 89.13% (41/46) in the normal iPTH group, and 60.77% (30/43) in the high iPTH group ( χ2 = 6.60, P = 0.037). Other parameters showed significant differences among the groups: neutrophil count was 3.60 (2.94, 4.79) × 10 9/L in the low iPTH group, 4.08 (3.16, 4.88) × 10 9/L in the normal iPTH group, and 5.21 (4.08, 6.75) ×10 9/L in the high iPTH group ( Z = 25.64, P < 0.001); lymphocyte count was 1.51 (1.13, 1.85) × 10 9/L, 1.18 (1.00, 1.68) × 10 9/L, and 1.10 (0.75, 1.66) × 10 9/L, respectively ( Z = 8.25, P = 0.016); monocyte count was 0.47 (0.36, 0.62) × 10 9/L, 0.53 (0.42, 0.70) × 10 9/L, and 0.43 (0.33, 0.54) × 10 9/L, respectively ( Z = 8.15, P = 0.017); serum albumin levels were (37.26 ± 5.77) g/L, (36.31 ± 5.68) g/L, and (41.53 ± 4.90) g/L, respectively ( t = 10.85, P < 0.001); creatinine levels were 214.00 (148.00, 343.00) μmol/L, 462.00 (338.50, 682.25) μmol/L, and 835.50 (702.50, 960.75) μmol/L, respectively ( Z = 74.65, P < 0.001); serum calcium levels were 2.19 (2.11, 2.28) mmol/L, 2.16 (2.04, 2.26) mmol/L, and 2.32 (2.10, 2.49) mmol/L, respectively ( Z = 11.77, P = 0.003); serum phosphate levels were 1.21 (1.04, 1.49) mmol/L, 1.47 (1.27, 1.83) mmol/L, and 1.99 (1.65, 2.49) mmol/L, respectively ( Z = 48.72, P < 0.001); SII values were 362.75 (292.68, 639.92), 491.03 (380.12, 715.77), and 851.50 (525.23, 1 149.72), respectively ( Z = 33.02, P < 0.001); and MLR values were 0.30 (0.24, 0.43), 0.43 (0.30, 0.52), and 0.35 (0.28, 0.61), respectively ( Z = 9.02, P = 0.011). All differences among the three groups were statistically significant (all P < 0.05). There were no statistically significant differences among the groups regarding age, gender, height, body mass index, smoking history, alcohol consumption history, prevalence of diabetes, platelet count, serum total protein, uric acid, triglycerides, total cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol (all P > 0.05). Multivariate logistic regression analysis indicated that elevated SII ( OR = 1.003, P = 0.024) was an independent risk factor for increased serum iPTH ( P < 0.05). Receiver operating characteristic analysis showed that the area under the curve for SII predicting high iPTH in patients with stage 5 CKD was 0.774 ( P < 0.001). Conclusions:In patients with stage 5 CKD, elevated creatinine, serum calcium, and SII are independent risk factors for increased serum iPTH, and SII has predictive value for the occurrence of high iPTH in patients with CKD.

Objective:To analyze the effect of precipitation on road traffic injuries (RTI) in Zhejiang Province.Methods:The RTI surveillance and meteorological data from 2009 to 2022 in Zhejiang Province were collected. Based on the time-stratified case-crossover design, the precipitation of case day and control day was compared, and the distributed lag nonlinear model was applied to analyze the correlation of precipitation and RTI. Stratified analyses were conducted to analyze the effect modification of gender, age, injury location, and temperature. An attributable fraction was used to assess the burden of RTI caused by precipitation.Results:A total of 239 970 RTIs were monitored in Zhejiang Province from 2009 to 2022, averaging 46 daily cases. The distributed lag nonlinear model showed that compared with no rain, the risk of RTI increased first and then decreased with the increase of precipitation. The risk of RTI was the highest when the precipitation was 30.99 mm ( OR=1.08, 95% CI: 1.05-1.11). The adverse effects on RTI mainly occurred on the day of precipitation, and it showed insignificant or protective effects with the extension of lag days. 1.34%(95% CI: 1.31%-1.36%) of RTI could be attributed to precipitation. Stratified analysis showed that gender, age, injury location, and temperature may modify the effect of precipitation on RTI. Precipitation caused a heavier burden on RTI in subgroups aged 18-64, females, and occurring on roads and in low temperatures. Conclusions:Precipitation can increase the risk of RTI. People aged 18-64 or females are the key groups for RTI prevention, and prevention and control efforts of precipitation-related RTI should be increased in road and low-temperature environments.

Objective:To explore the relationships between physical activity and cognitive impairment in older adults aged ≥65 years in longevity areas in China.Methods:A total of 6 081 older adults aged ≥65 years from the Healthy Ageing and Biomarkers Cohort Study in China in 2021 were included in this study. Information about their demographic characteristics, lifestyles, and chronic disease histories were collected, the intensity of physical activity was evaluated by using Physical Activity Scale for the Elderly, and the cognitive function was evaluated by using Mini-Mental State Examination Scale (Chinese version). Multifactorial logistic regression model was used to analyze the associations between different levels and types of physical activity and cognitive impairment in older adults.Results:In the 6 081 older adults, 1 829 (30.1%) had cognitive impairment. After adjusting for confounders, older adults with T2 and T3 levels of physical activity had lower risks for cognitive impairment compared with those with T1 levels of physical activity, with ORs of 0.47 (95% CI: 0.40-0.55) and 0.22 (95% CI: 0.18-0.28). The results of different types of physical activities showed that the ORs in leisure activity T2 and T3 groups were 0.52 (95% CI: 0.44-0.63) and 0.49 (95% CI: 0.41-0.58), and the ORs in housework activity T2 and T3 groups were 0.36 (95% CI: 0.30-0.42) and 0.19 (95% CI: 0.16-0.24). There was no significant association between work-related activity and cognitive impairment. Conclusion:There is a negative association between the intensity level of physical activity and cognitive impairment, and active leisure and household activities might reduce the risk for cognitive impairment.

Objective:To systematically analyze the prevalence and influencing factors of psychiatric comorbidities in refractory epilepsy (RE) .Methods:The literature on the prevalence and/or influencing factors of psychiatric comorbidities in adults with RE was electronically searched in China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database, PubMed, Web of Science, Embase, CINAHL, OVID, UpToDate, and Cochrane Library. The search period was from the establishment of the database to July 31, 2024. Two researchers independently conducted literature screening, quality assessment and data extraction, and used RevMan 5.4 for Meta-analysis.Results:A total of 11 papers were included, with a total sample size of 1 953 cases, with a prevalence of 52.00% (cross sectional studies) and 53.00% (cohort studies) . Gender [ OR=4.76, 95% CI (3.69, 6.15) ] , epilepsy disease perception [ OR=1.10, 95% CI (1.01, 1.19) ] , seizure type [ OR=1.63, 95% CI (1.23, 2.15) ] , seizure frequency [ OR=1.54, 95% CI (1.04, 2.29) ] , epileptogenic foci location [ OR=2.72, 95% CI (1.69, 4.37) ] , disease duration [ OR=1.76, 95% CI (1.39, 2.24) ] , and medication [ OR=3.26, 95% CI (2.09, 5.08) ] were the influencing factors of psychiatric comorbidity in RE. Conclusions:The prevalence of psychiatric comorbidities in patients with RE is high, and studies of influencing factors lack specificity. Clinical monitoring of this population should be strengthened, and relevant influencing factors should be comprehensively analyzed to provide intervention targets for early preventive management and to safeguard the long-term management of patients with epilepsy.