ObjectiveTo investigate the uric acid-lowering effects and mechanisms of acacetin on hyperuricemia （HUA） in mice. MethodsOteracil potassium and adenine were used to establish the mouse model of HUA. Male Kunming mice （n=48） were randomized into six groups： control， model， low-dose （12.5 mg·kg^-1） acacetin， medium-dose （25 mg·kg^-1） acacetin， high-dose （50 mg·kg^-1） acacetin， and allopurinol （10 mg·kg^-1）. Each group received continuous gavage administration for 21 days. An automatic biochemical analyzer was used to measure the levels of uric acid （UA）， creatinine （Cr）， urea nitrogen （BUN）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST）. Additionally， the activity of xanthine oxidase （XOD） in the liver and the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-18 in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining. Western blot was employed to determine the levels of glucose transporter 9 （GLUT9）， urate transporter 1 （URAT1）， phospho-NF-κB p65 （p-NF-κB p65）， and nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 （NLRP3） in the renal tissue. ResultsCompared with the control group， the model group showed elevated levels of UA， Cr， BUN， ALT， and AST， increased activity of XOD in the liver（P<0.01）， raised levels of TNF-α， IL-1β and IL-18 in the serum（P<0.01）， and significantly up-regulated expression of GLUT9， URAT1， p-NF-κB p65， and NLRP3 in the renal tissue（P<0.01）. Compared with the model group， acacetin reduced the UA level in a dose-dependent manner， significantly improved liver and kidney functions， decreased the XOD activity in the liver， ameliorated the pathological changes in the renal tissue， down-regulated the expression of GLUT9， URAT1， p-NF-κB p65 and NLRP3 in the renal tissue（P<0.01）， and lowered the levels of TNF-α， IL-1β， and IL-18 in the serum（P<0.01）. ConclusionAcacetin can ameliorate HUA by decreasing uric acid production， increasing uric acid excretion， and inhibiting the NF-κB/NLRP3 signaling pathway. Therefore， acacetin may be a potential drug for the treatment of HUA.

ObjectiveTo establish three standardized rehabilitation unit models covering acute, critical and comprehensive recovery stages for traumatic brain injury (TBI) that fit the whole-course characteristics, clarify their multidisciplinary collaborative framework, standardized procedures, and information management system, and verify the clinical effectiveness of this staged rehabilitation unit on long-term functional prognosis and in-hospital complications of TBI patients. MethodsThis study was conducted at two stages: model construction and efficacy verification. At the first stage, TBI rehabilitation units for acute, critical and recovery stages were established in the Department of Neurosurgery, Intensive Care Unit and Department of Rehabilitation Medicine, respectively, with unified multidisciplinary team configuration, standardized assessment and treatment protocols, collaborative workflows, and a dedicated information management system. At the second stage, 324 TBI patients admitted to the newly built rehabilitation units from July, 2023 to July, 2025 were enrolled as the observation group, and 167 TBI patients receiving traditional management from January, 2018 to December, 2022 were retrospectively selected as the control group. The primary outcomes were 1-year post-injury Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) scores. Secondary outcomes included the incidence of in-hospital complications and the mean indwelling time of tracheal intubation, gastric tube and urinary catheter. ResultsThe 1-year GOS score was significantly higher (t = -7.836, P < 0.001), and the DRS score was significantly lower (t = -6.742, P < 0.001) in the observation group than in the control group. The overall incidence of complications was significantly lower in the observation group than in the control group (χ² = 18.762, P < 0.001). The incidences of pulmonary infection, urinary tract infection, pressure ulcer, lower extremity venous thrombosis and joint contracture deformity were all significantly reduced (χ² > 4.328, P < 0.05). The indwelling time of tracheal intubation, gastric tube and urinary catheter was significantly shorter in the observation group than in the control group (t > 10.276, P < 0.001). ConclusionThe acute-critical-comprehensive three-stage standardized TBI rehabilitation unit could significantly improve the long-term functional outcomes of TBI patients, reduce the incidence of complications, and shorten the indwelling time of invasive tubes through multidisciplinary collaboration, whole-course standardized management and information-based quality control. This model conforms to the pathological and functional laws of TBI, realizes seamless whole-course connection from acute treatment to recovery rehabilitation, and has good clinical feasibility and promotion value. It can provide evidence-based evidence and practical reference for the homogenized and standardized development of TBI rehabilitation in China.

Objective To explore the risk factors of physical frailty in elderly patients with multiple digestive tract diseases, and to provide reference for clinical intervention. Methods The clinical data of 310 elderly patients with digestive tract diseases admitted to the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University between May 2020 and May 2025 were retrospectively analyzed. The patients with physical frailty were included in the frailty group, and the remaining patients were assigned into the non-frailty group. The clinical data of the two groups were observed and compared. The influencing factors were explored by multivariate logistic regression analysis, and the prediction model was constructed. Results Among the 310 patients, 77 cases (24.84%) had physical frailty, and 233 cases (75.16%) did not experience frailty. The proportion of patients aged≥75 years, Charlson Comorbidity Index (CCI), Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls (SARC-F) score, 4m walking time and the proportion of patients who failed to complete full-foot-length standing in the frailty group were higher than those in the non-frailty group, while the Mini Nutritional Assessment-Short Form (MNA-SF) score, grip strength, Tinetti balance and gait scale score were lower compared to the non-frailty group (P<0.05). Multivariate logistic regression analysis suggested that SARC-F score was an independent risk factor of physical frailty in elderly patients with digestive tract diseases, and Tinetti score was an independent protective factor (P<0.05). The prediction model was constructed based on multivariate results, and Hosmer-Lemeshow goodness-of-fit test revealed that the model had a good fitting degree (P>0.05). ROC curve analysis indicated that the area under the curve of the model was 0.96 (95%CI: 0.93-1.00). Conclusion The incidence rate of physical frailty is relatively high in elderly patients with digestive tract diseases, and SARC-F score and Tinetti score are associated with its occurrence.

Objective To establish a prediction model for the occurrence of non-occupational carbon monoxide poisoning events in Beijing, and to provide scientific basis and theoretical support for the prevention and warning of poisoning events. Methods Based on the monitoring data of non-occupational carbon monoxide poisoning events in Beijing from 2016 to 2024, the seasonal ARIMA model and seasonal index model were established to analyze the data and predict the occurrence of events. Results Between 2016 and 2024, a total of 436 cases of non-occupational carbon monoxide poisoning were reported in Beijing, showing a downward trend. The established SARIMA model and seasonal index model were SARIMA (1,0,0) (1,1,0) 12, Yt = (-0.0339t+5.8863) × St, and the average relative errors were 65.42% and 29.19%, respectively. In terms of months, the SARIMA model had better predictive performance during April and summer (June to August), while the seasonal index model was superior in other months. By combining the two models, the predicted number of events in 2025 was as follows: 3, 2, 2, 3, 1, 5, 2, 7, 1, 1, 1, and 2. Conclusion The seasonal index model has the best prediction effect on the non-occupational carbon monoxide poisoning events in Beijing throughout the year, and the number of summer events predicted by SARIMA model is closer to the actual values. The two models can be combined to predict the trend of non-occupational carbon monoxide poisoning, which provides a scientific basis for the prevention and control of carbon monoxide poisoning in the future.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

Objective:To investigate the interventional and protective effect of low-dose L-carnitine(LC)against reproductive system damage in male Wistar rats during acute exposure to simulated high-altitude environment.Methods:A total of 24 specific pathogen-free male Wistar rats,aged 12 weeks,were randomly divided into control group,high-altitude model group,and LC intervention group[intraperitoneal injection of LC at a dose of 50 mg/(kg·d)],with 8 rats in each group.The rats in the control group were fed under normal conditions(at an altitude of approximately 1 500 m),those in the high-altitude model group,and those in the LC intervention group were fed in a hypobaric oxygen chamber(at a simulated alti-tude of 6 000 m).The rats were sacrificed after 3 days.The testis was collected to calculate testicular index;the semen was collected from the epididymis,and the Weili sperm quality analysis system was used to assess sperm quality;blood samples were collected from the abdominal aorta,and ELISA kits were used to measure the serum levels of testosterone(T),luteinizing hormone(LH),and follicle-stimulating hormone(FSH);testicular tissue samples were collected,and biochemical kits were used to measure the activity of reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD);testicular tissue was collected to prepare HE and electron microscopy sections,and a light microscope and a transmission electron microscope were used for observation.Results:Com-pared with the blank control group,the high-altitude model group had significant increases in the levels of T,LH,and FSH(P<0.01),testicular tissue damage under the light microscope,and changes in the morphology of spermatogenic cells,including mitochondrial al-terations,membrane edema,loss of cristae,swelling of the matrix,and local dissolution,as well as significant increases in the levels of ROS and MDA(P<0.01)and a significant reduction in SOD activity(P<0.01).Compared with the high-altitude model group,the LC intervention group had a significant increase in the level of T(P<0.01),significant reductions in the levels of FSH and LH(P<0.01),and significant improvements in the pathological changes of testicular tissue,with no marked mitochondrial injury,and there were sig-nificant reductions in the levels of ROS and MDA(P<0.01)and a significant increase in SOD activity(P<0.01).There was no signifi-cant difference in testicular index between groups(P>0.05).The high-altitude model group had a significantly lower sperm count than the blank control group(P<0.05),while there was no significant difference in sperm count between the LC intervention group and the blank control group(P>0.05);there was no significant difference in sperm motility between groups(P>0.05).Conclusion:Low-dose LC can improve reproductive system damage in rats during acute exposure to simulated high-altitude environment,possibly by alleviat-ing oxidative stress response.