Diseases of the central nervous system have become a growing global health concern. At present， there are many adverse reactions in the treatment with Western medicine. In contrast， traditional Chinese medicine has shown unique efficacy and rich clinical practice accumulation in diseases of the central nervous system. As a traditional Chinese medicine， Bupleuri Radix has played an important role in the treatment of neurological diseases through multi-target regulation， multi-pathway intervention， and multi-pathway mechanism of action. In recent years， with the in-depth study of the pharmacological effects of Bupleuri Radix， it has been found that the active ingredients such as saikosaponin， baicalin， quercetin， and kaempferol in Bupleuri Radix can be used as the main material basis for the treatment of neurological diseases. The results of this study showed that in neurodegenerative diseases， active ingredients of Bupleuri Radix can inhibit β-amyloid （Aβ） deposition and abnormal phosphorylation of microtubule-associated protein （Tau protein） in Alzheimer's disease， regulate the nuclear factor-κB/nuclear factor E₂ related factor 2 （NF-κB/Nrf2） pathway to play the anti-inflammatory role， and alleviate α-Synuclein （α-Syn） aggregation and mitochondrial damage in Parkinson's disease. In epilepsy， depression， and cerebral ischemia， they can improve symptoms by regulating neurotransmitters， oxidative stress， and apoptosis pathways， and inhibit brain glioma proliferation. However， the mechanism of action has not been fully elucidated， and the complexity of compound components and poor blood-brain barrier penetration limit their clinical application. In the future， it is necessary to integrate multi-omics， network pharmacology， and nano-delivery technologies， focus on the optimization of active ingredient group compounds and the precise guidance of biomarkers， accelerate the development of innovative therapies for Alzheimer's disease， Parkinson's disease， and other diseases for laying a solid theoretical foundation for further development and application and inspiring new research ideas.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

Objective To optimize the extraction, separation and purification process of Actinoside E. Methods Single factor experiment combined with orthogonal test was used to determine the optimal extraction process of Actinoside E using its content as an index. The extracts were separated and purified by optimizing the chromatographic conditions of macroporous resin, silica gel and ODS column. Results 25 times amount of 55% ethanol with heating reflux at 95℃ for one hour were used as the optimal extraction process of Actinoside E. The optimum separation and purification process was as follows: D101 macroporous resin column was eluted with 7 BV of 50% ethanol, silica gel column was eluted with 5 BV of ethyl acetate-ethanol（10∶1）and 50% methanol eluted fraction was purified repeatedly by ODS column to obtain Actinoside E. The transfer rate of Actinoside E in the whole process was 53.70%, the yield was 0.35%, and the purity was 99.9%. Conclusion The process is stable and viable, which can provide material foundation for the development and utilization of Actinoside E.

Objective To explore the correlation between lymph node metastasis and clinicopathological features of lung adenocarcinoma with diameter≤3 cm. Methods The clinicopathologic data of the patients with lung adenocarcinoma≤3 cm in diameter were retrospectively analyzed. The relationship between lymph node metastasis and age, gender, smoking history, pathological subtype, tumor diameter, pleural invasion, vascular invasion and other factors was analyzed. The risk factors of lymph node metastasis were analyzed by univariate and multivariate logistic regression. Results Finally 1 718 patients were collected, including 697 males and 1 021 females with an average age of (58.89±9.85) years. The total lymph node metastasis rate was 12.9%, among whom 452 patients of adenocarcinoma in situ and minimally invasive adenocarcinoma did not have lymph node metastasis, and the lymph node metastasis rate of invasive lung adenocarcinoma was 17.5%. Multivariate analysis showed that tumor diameter, micropapillary subtype, solid subtype, micropapillary component, solid component, vascular invasion and pleural invasion were independent risk factors for lymph node metastasis of invasive lung adenocarcinoma with diameter≤3 cm (P<0.05). While age, lepidic subtype and lepidic component were independent protective factors for lymph node metastasis (P<0.05). Conclusion Clinicopathological features can help predict lymph node metastasis of lung adenocarcinoma with diameter≤3 cm.

Objective To longitudinally investigate the characteristics of postoperative weight changes in patients with esophageal cancer and analyze its influencing factors, which can provide certain guidance for nutritional intervention in patients with esophageal cancer. Methods Patients with esophageal cancer who underwent surgical treatment at the Sichuan Cancer Hospital from December 2020 to February 2022 were prospectively included. The general information questionnaire and body composition analyzer were used to longitudinally investigate the patients’ weight and body composition before surgery (T0), 1 month after surgery (T1), 3 months after surgery (T2) and 6 months after surgery (T3), and the change characteristics were analyzed. The generalized estimating equation was used to analyze the influencing factors for postoperative weight changes in patients with esophageal cancer. Results A total of 130 patients were enrolled, including 110 males and 20 females, aged 42-79 (63.33±8.16) years. The weight and body composition of patients with esophageal cancer showed a continuous slow downward trend within 6 months after surgery. The weight loss rate of patients at 1, 3, and 6 months after surgery was 5.10%, 7.76%, and 9.86%, respectively. The analysis results of the influencing factors for postoperative weight showed that patients with the following characteristics had more weight loss: female (β=−7.703, P=0.001), ≥60 years (β=−3.657, P=0.010), smoking (β=4.622, P=0.010), low tumor differentiation degree (β=4.314, P=0.039), and high frequency of eating (β=−3.400, P=0.008). Conclusion Weight loss is an important health problem for patients with esophageal cancer after surgery, and patients have a continuous downward trend in weight within 6 months after surgery. Medical staff should pay special attention to the patients who are female, ≥60 years, having smoking history and low tumor differentiation degree.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

OBJECTIVE To systematically evaluate risk prediction models for chemotherapy-induced myelosuppression in pediatric patients with malignant tumors， evaluate their modeling strategies， key predictors， and predictive performance， and provide evidence-based references for clinical decision-making and research. METHODS A literature search was conducted across 11 databases， including CNKI， Wanfang Data， and PubMed， for relevant studies published before April 2025. Two reviewers independently performed literature screening and data extraction， and the risk of bias and applicability of the models were evaluated using the PROBAST tool. RESULTS Ultimately， seven studies were selected， of which four were English articles and three were Chinese articles， involving 12 risk prediction models. Although model discrimination was good （AUC 0.748-0.981）， only two models underwent external validation； furthermore， calibration was inadequately reported in three studies. PROBAST indicated that all models exhibited a high risk of bias， with major issues including a predominance of retrospective designs， inadequate sample representativeness， and lack of blinding. However， in terms of applicability， all models received favorable evaluations. In terms of modeling methods， most studies employed traditional logistic regression approaches to construct models， while only a minority introduced machine learning algorithms and conducted systematic comparisons among multiple algorithms. Models developed using machine learning methods significantly outperformed those constructed with traditional statistical methods. CONCLUSIONS The existing risk prediction models for myelosuppression after chemotherapy in children with malignant tumors demonstrate potential in clinical risk early warning. However， they generally suffer from design and methodological limitations， such as a predominance of retrospective single-center designs， few events per variable， opaque handling of missing data， and inconsistent reporting of model coefficients. Future studies should adopt prospective designs， incorporate machine learning with key clinical predictors， and follow TRIPOD reporting guidelines to enhance scientific rigor and clinical utility.

This study employed the drug affinity responsive target stability (DARTS) technique to investigate the molecular mechanism of the antipsychotic drug penfluridol against melanoma, revealing the biological pathway to exert its effect on the HSPA6/p53/p21 signaling axis. Experiments such as the methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell colony formation ability assay confirmed that penfluridol could significantly downregulate the expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) in melanoma A375 and B16 cells, induce cell cycle arrest in the G1 phase, and thus inhibit the proliferation of melanoma cells. Meanwhile, the results of Western blot, Hoechst 33342 staining and Annexin V-FITC/PI double staining experiments showed that penfluridol could significantly downregulate the expression of Bcl-2 and upregulate the expression of Bax and cleaved caspase-3, inducing cell apoptosis. Further, the DARTS technique was used to identify heat shock 70 kD protein 6 (HSPA6) as the key target bound by penfluridol. Penfluridol activates the p53/p21 pathway by upregulating HSPA6. Knocking down HSPA6 reverses not only the activation of the p53/p21 pathway mediated by penfluridol but also the associated cell cycle arrest and apoptosis. Animal experiments on tumor-bearing mice also confirmed that knocking down HSPA6 could reverse the in vivo anti-tumor activity of penfluridol. This study clarified that penfluridol can inhibit the progression of melanoma by targeting HSPA6 to activate the p53/p21 signaling axis, providing a new perspective for the repositioning of antipsychotic drugs in cancer treatment.