Objective To evaluate the predictive value of different machine learning models constructed in a multicenter environment for potential organ donors and verify their clinical application feasibility. Methods The study included 2 000 inpatients admitted to five domestic tertiary hospitals from January 2020 to December 2023, who met the criteria for potential organ donation assessment. They were randomly divided into a training set and an internal validation set (7∶3). Another 300 similar patients admitted to the First Affiliated Hospital of Harbin Medical University from January 2024 to April 2025 were included as an external validation set. The area under the curve (AUC), sensitivity, specificity, accuracy and F1-score of three models were compared, and the consistency of the potential organ donor determination process was tested. Multivariate logistic regression analysis was used to identify predictive factors of potential organ donors. Decision curve analysis (DCA) was employed to verify the resource efficiency of each model, and the threshold interval and intervention balance point were assessed. Results Apart from age, there were no significant differences in other basic characteristics among the centers (all P>0.05). The consistency of the potential organ donor determination process among researchers in each center was good [all 95% confidence interval (CI) lower limits >0]. In the internal validation set, the XGBoost model had the best predictive performance (AUC=0.92, 95% CI 0.89-0.94) and the best calibration (P=0.441, Brier score 0.099). In the external validation set, the XGBoost model also had the best predictive performance (AUC=0.91, 95% CI 0.88-0.94), outperforming logistic regression and random forest models. Multivariate logistic regression showed that mechanical ventilation had the greatest impact (odds ratio=2.06, 95% CI 1.54-2.76, P<0.001). DCA indicated that the XGBoost model had the highest net benefit in the threshold interval of 0.2-0.6. The “treat all” strategy only had a slight advantage at extremely low thresholds. The recommended threshold interval, which balances intervention costs and clinical benefits, considers ≥50% positive predictive value (PPV) and ≤50 referrals per 100 high-risk patients. Conclusions The XGBoost model established in a multicenter environment is accurate and well-calibrated in predicting potential organ donors. Combined with DCA, it may effectively guide the timing of clinical interventions and resource allocation, providing new ideas for the assessment and management of organ donation after brain death.

Peripheral neurotoxicity represents one of the most severe dose-limiting adverse reactions associated with oxaliplatin， with genetic polymorphisms playing a significant role in oxaliplatin-induced peripheral neuropathy （OIPN）. OIPN can be categorized as acute or chronic based on onset timing. The former presents clinically as sensory abnormalities or even motor disorders， while the latter presents clinically as limb sensory disorders that persist， numbness or pain in the hands and feet. The transporter genes OCT2， OCTN2， and NHE1 may be implicated in OIPN； drug-metabolizing enzyme gene GSTP1 Ile105Val， DPYD rs1801265， voltage-gated sodium channel （NaV） gene SCN4A rs2302237， SCN9A rs6746030， SCN10A rs12632942， and other associated genes such as HLA-G rs1610696， rs371194629 and CCNH rs2230641， rs3093816 are associated with severe OIPN. Conversely， DNA repair-related gene XRCC1 rs23885， NaV gene SCN9A rs3750904， rs12478318 and rs6754031 are associated with reduced OIPN risk. In the future， the genetic research findings on OIPN can be translated into clinical applications， ultimately achieving individualized precision medicine for patients.

ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

[摘 要] 目的：探究环状RNA hsa_circ_0081621对人喉鳞状细胞癌AMC-HN-8和TU177细胞恶性生物学行为的影响。方法：常规培养AMC-HN-8和TU177细胞，用转染试剂将si-NC、si-hsa_circ_0081621、空载体（vector）和hsa_circ_0081621过表达载体（hsa_circ_0081621-OE）转染至AMC-HN-8和TU177细胞，分别记作si-NC、si-hsa_circ_0081621、vector和hsa_circ_0081621-OE组。用CCK-8法、克隆形成实验、划痕愈合实验和Transwell小室实验分别检测敲减或过表达hsa_circ_0081621对AMC-HN-8和TU177细胞增殖、迁移和侵袭能力的影响。结果：在AMC-HN-8和TU177中成功地敲减或过表达了hsa_circ_0081621；敲减或过表达hsa_circ_0081621能显著抑制或促进AMC-HN-8和TU177细胞的增殖、迁移和侵袭能力（P < 0.01或P < 0.001或P < 0.000 1）。结论：hsa_circ_0081621可促进人喉鳞状细胞癌AMC-HN-8和TU177细胞的恶性生物学行为。

To investigate the genetic relatedness between carbapenem-resistant Klebsiella pneumoniae(CRKP) strains isolated from intestinal colonization and subsequent bloodstream infections.

Cardiovascular diseases are the leading cause of mortality, posing a significant threat to human health due to the high incidence rate. Atherosclerosis, a chronic inflammatory disease, serves as the primary pathological basis for most such conditions. The incidence of atherosclerosis continues to rise, but its pathogenesis has not been fully elucidated. As an important member of the small GTPase superfamily, Ras-association proximate 1 (Rap1) is an important molecular switch involved in the regulation of multiple physiological functions including cell differentiation, proliferation, and adhesion. Rap1 achieves the utility of the molecular switch by cycling between Rap1-GTP and Rap1-GDP. Rap1 may influence the occurrence and development of atherosclerosis in a cell-specific manner. This article summarizes the potential role and mechanism of Rap1 in the progression of atherosclerosis in different cells, aiming to provide new therapeutic targets and strategies for clinical intervention.
Humans ; Atherosclerosis/metabolism* ; rap1 GTP-Binding Proteins/physiology* ; Animals ; Cell Differentiation ; Cell Adhesion ; Cell Proliferation

Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.
Animals ; Mesenchymal Stem Cells/metabolism* ; Caveolin 1/genetics* ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; Cell Differentiation/drug effects* ; Female ; Signal Transduction/drug effects* ; Flavonoids/administration & dosage* ; Protein Serine-Threonine Kinases/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cells, Cultured ; Humans

This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals ; Male ; Rats ; Yang Deficiency/physiopathology* ; Metabolomics ; Kidney/physiopathology* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Cistanche/chemistry* ; Kidney Diseases/metabolism* ; Testis/metabolism* ; Humans ; Reproduction/drug effects* ; Testosterone/blood*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Qualitative and quantitative analysis methods for chemical components of different processed products of Corni Fructus were established to systematically characterize and identify these components, and the content of the main differential components was determined. The chemical components of different processed products of Corni Fructus were collected using ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS). Through analysis of self-built databases, literature, and reference standards, a total of 93 components were obtained, including 19 iridoids, 15 flavonoids, 16 organic acids, eight triterpenoids, eight tannins, four amino acids, two polysaccharides, five olefins, and 16 other compounds. Additionally, by using multivariate statistical methods, the differential components between different processed products of Corni Fructus were screened under the conditions of VIP>1.0 and FC<0.5 or FC>2.0 and P<0.05. The PCA and OPLS-DA results showed differences in the chemical components between different processed products of Corni Fructus. A total of 21 differential components were screened, including tartaric acid, morroniside, and rutin. On this basis, ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS) was used to determine the content of 10 main common differential components, including gallic acid, morroniside, ursolic acid, loganin, swertiamarin, rutin, 5-hydroxymethylfurfural, cornuside Ⅰ, quercetin, and oleanolic acid. The above 10 components showed a good linear relationship within the determined concentration range, with the precision, stability, repeatability, and sample recovery rate all meeting the requirements. Compared with that in Corni Fructus, the content of iridoid glycosides in wine-prepared Corni Fructus and wine-and honey-prepared Corni Fructus decreased, while the content of gallic acid, rutin, quercetin, 5-hydroxymethylfurfural, ursolic acid, and oleanolic acid increased. Compared with wine-prepared Corni Fructus, wine-and honey-prepared Corni Fructus showed varying degrees of increase in all other components, except for a slight decrease in gallic acid content. In summary, this study clarified the influence of different processing methods on the chemical components of Corni Fructus, providing a theoretical basis for the scientific connotation, overall quality evaluation, and clinically rational application of Corni Fructus processing in the future.
Tandem Mass Spectrometry/methods* ; Chromatography, High Pressure Liquid/methods* ; Cornus/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Fruit/chemistry*