ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveTo review the parameters, effects, mechanisms, potential risks and research status of transcranial direct current stimulation (tDCS) in intervening motor skills among adults. MethodsA systematic search of Web of Science, PubMed, EBSCO and CNKI databases was conducted for studies related to tDCS in intervening motor skills among adults, with publication from inception to October, 2025. Data extraction and scoping review were performed, with literature quality assessed using the Physiotherapy Evidence Database (PEDro) scale. ResultsA total of 38 studies were included, from China, Germany, the United States, the United Kingdom, Brazil, Canada, Italy, Spain, Iran and Ireland, involving 1 087 participants. The subjects were adults, including non-athletes and athletes. The outcomes included the performance of opened motor skills and closed motor skills, such as basketball shooting accuracy and golf putting test scores. Anodal tDCS intervention with a stimulation intensity of 1 mA to 2 mA; a stimulation duration of ten to 25 minutes; and an electrode patch of 35 cm² (3.14 cm² to 9 cm² for high-precision tDCS) improved motor skill performance in both athletes and non-athletes. For opened motor skills, tDCS targeting the primary motor cortex was better; for closed motor skills, tDCS targeting the dorsolateral prefrontal cortex was more effective. ConclusiontDCS may have a certain facilitating effect on the performance of opened and closed motor skills in adults. However, significant heterogeneity exists in the intervention environments, stimulation protocols and experimental designs of existing studies, resulting in ongoing controversy over its efficacy.

ObjectiveTo investigate the distribution characteristics and correlation of paired oral and esophageal microbiota in patients with esophageal squamous cell carcinoma （ESCC）. MethodsA total of 46 pathologically confirmed ESCC patients were enrolled， and oral swabs and cancerous tissue samples were collected. The microbial composition was analyzed using 16S rRNA gene sequencing， and bioinformatics methods were employed to compare the microbiota diversity， compositional differences， and correlations between the two sites. ResultsThe Alpha diversity of the oral microbiota in ESCC patients was significantly higher than that of their esophageal microbiota， though the overall community structure was similar between the two sites. LEfSe analysis revealed that Spirochaetes， Prevotella， Catonella， Enterococcus， Fusobacterium periodonticum， Veillonella parvula， Capnocytophaga sputigena， and Neisseria subflava were significantly enriched in ESCC tumor tissues. In contrast， Actinobacteria， Proteobacteria， Streptococcus， Neisseria， Haemophilus， Streptococcus mitis， Haemophilus parainfluenzae， Porphyromonas gingivalis， Haemophilus haemolyticus， and Prevotella tannerae were significantly enriched in the oral cavity. Correlation analysis demonstrated significant associations between the two sites at taxonomic levels such as Spirochaetes， Treponema， Granulicatella elegans， Neisseria macacae， Treponema amylovorum， Fusobacterium periodonticum， and Neisseria meningitidis （P<0.05）. ConclusionThe oral and esophageal microbiota in ESCC patients exhibit both distinct differences and similarities. Oral microbiota may influence the esophageal microenvironment through migration or local immune modulation.

ObjectiveTo compare the performance of different automatic evaluation methods for detecting pattern hallucinations generated by large language models （LLMs） in traditional Chinese medicine （TCM） syndrome differentiation and to identify a strategy with higher overall discriminative performance against expert manual judgment. MethodsA standardized TCM syndrome-differentiation dataset containing 598 cases was constructed from case reports published in Chinese core journals indexed by Peking University Core Journals or Chinese Science Citation Database. Each of the 598 cases was submitted to five Chinese LLMs， with each model generating one syndrome-pattern output per case， yielding 2990 outputs in total. The 598 outputs generated by Qwen3-Next-80B-A3B-Thinking were independently annotated for syndrome-pattern hallucinations by two licensed TCM physicians with intermediate or higher professional titles. Disagreements were adjudicated by a third licensed TCM physician with a senior associate professional title and more than 10 years of clinical experience. The resulting consensus annotations served as the reference labels for training and validating the automated evaluation method. Based on these reference labels， three categories of automated evaluation methods were developed and compared following a progressive strategy from text-level semantic similarity， to syndrome-element structural consistency， and finally multi-feature fusion. Method A employed sentence-embedding models based on semantic similarity between pattern texts. Method B adopted a rule-based threshold method using weighted Jaccard coefficients of disease-location and disease-nature syndrome elements. Method C utilized a machine-learning classifier integrating syndrome-element matching scores， missing and redundant syndrome-element counts， and multiple semantic-similarity features. Five-fold cross-validation was used to evaluate the discriminative performance of each method against manual judgment. The optimal method was then applied to uniformly assess the pattern hallucination rates of five LLMs. ResultsIn method A， text2vec-large-chinese showed best overall performance， with an area under the receiver operating characteristic curve （AUROC）， area under the precision-recall curve （PR-AUC）， F1-score， sensitivity， and specificity of 0.849， 0.884， 0.794， 0.801， and 0.691， respectively. In method B， the corresponding metrics of the rule-based syndrome-element Jaccard threshold method were 0.848， 0.851， 0.817， 0.845， and 0.684， respectively； those of the LLM-based syndrome-element Jaccard method were 0.872， 0.906， 0.795， 0.764， and 0.780， respectively. In method C， the multilayer perceptron （MLP） classifier showed the best overall performance， with AUROC， PR-AUC， F1-score， sensitivity， and specificity of 0.933， 0.951， 0.871， 0.857， and 0.846， respectively. Under the unified evaluation framework combining DeepSeek-R1 syndrome-element extraction and MLP classifier， the estimated pattern hallucination rates of the five LLMs ranged from 56.0% to 77.4%. ConclusionAmong the three automatic evaluation methods， Method C integrating syndrome-element discrepancy features and text semantic features using an MLP classifier showed the highest overall discriminative performance against manual judgment， and is more suitable for evaluating syndrome hallucinations in LLM-based TCM syndrome differentiation tasks.

OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

Dissolvable microneedles(DMNs)offer significant advantages for vaccine delivery,including pain relief,saving drug dose,no contamination of sharp instruments and autonomous operation.The review introduces the materials,fabri-cation processes and physical characteristics of DMNs,focusing on its application in delivering various vaccines,such as influenza vaccines,COVID-19 vaccines,viral hepatitis vaccines and the measles-rubella vaccine.Current research dem-onstrates that DMNs provide significant advantages in enhancing vaccine immunogenicity,boosting vaccine stability and reducing vaccination costs.Yet,challenges confronting the development of DMNs remain in terms of unclear material me-tabolism,skin safety,difficulties in large-scale production and lack of quality standards and regulations.With the continu-ous progress of microneedle technique and constant improvement of policies and regulations,DMNs are expected to play an important role in boosting the convenience of vaccination and raising the coverage rate of vaccination,thereby making significant contributions to human health undertakings.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To understand the current research status, hot issues, and development trends of Taohong Siwu Decoction.Methods:Research literature about Taohong Siwu Decoction was retrieved from Wanfang Data, CBM, CNKI, and Chongqing VIP from January 1, 2014, to August 13, 2024. Excel 2024 software was used to analyze the annual number of publications, the source journals, literature types and the distribution of diseases and syndromes. CiteSpace 6.3.R3 software was used for visualization analysis on the authors, research institutions and key words.Results:A total of 2 519 articles were included, and the annual publication volume showed a fluctuating growth trend. There were 396 source journals, of which Medicine and Health published the most (80 articles); 208 authors were involved, and the core authors included Peng Daiyin of Anhui University of Chinese Medicine, Zhu Fuping of the First Affiliated Hospital of Hunan University of Chinese Medicine, Sun Shaoqiu of the Second Affiliated Hospital of Hunan University of Chinese Medicine and so on. The main research institutions in this field included Hunan University of Chinese Medicine and its affiliated hospitals. The high-frequency keywords included fracture, irregular menstruation, clinical efficacy, chloasma, Wuling Powder, experience of famous doctors, elderly, etc. Keywords could be clustered into 11 modules.Conclusions:The current research hotspots of Taohong Siwu Decoction mainly focus on the exploration of multi-system disease treatment, individualized syndrome differentiation and treatment, pharmacology and metabolic mechanism of Chinese materia medica, etc. Among them, the in-depth study of drug composition and metabolism, network pharmacology and mechanism is the research frontier in this field.

Objective:To investigate the improvement effect of the freeze-dried garlic powder on acute myocardial ischemia and its effect on phosphatidylinositol 3 kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/Akt/Nrf2) signaling pathway.Methods:SD rats were randomly divided into sham-operation group, model group, positive drug group, and garlic freeze-dried powder low-, medium-, and high-dosage groups using a random number table method, with 12 rats in each group. The garlic freeze-dried powder low-, medium-, and high-dosage groups were orally administered with 0.58, 1.16, and 2.32 g/kg of garlic freeze-dried powder solution, the positive reference drug group was orally administered with 0.26 g/kg of compound Danshen tablet solution, and the model group and sham-operation group were orally administered with equal volumes of distilled water once a day for 14 consecutive days. Except for the sham-operation group, all other groups were prepared with acute myocardial ischemia models in rats by ligating the left anterior descending coronary artery. Electrocardiogram testing was performed. The incidence of ventricular premature beats, ventricular tachycardia, and ventricular fibrillation in each group was counted. Myocardial infarction was observed through TTC staining, and the myocardial infarction rate was calculated; serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB), LDH, cardiac troponin T (cTnT), total antioxidant capacity (T-AOC), SOD, MDA, IL-1β, TNF-α levels were detected, and Western blot was used to detect myocardial tissue p-PI3K, p-Akt, Nrf2, HO-1 and Keap1 proteins.Results:Compared with the model group, the incidence of premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation in rats in each treatment group was reduced. Compared with the model group, the positive drug group and garlic freeze-dried powder medium- and high-dosage groups showed a decrease in myocardial infarction rate in rats ( P<0.05); compared with the model group, the levels of serum T-AOC and SOD in each treatment group increased ( P<0.05 or P<0.01), while the level of MDA decreased ( P<0.05 or P<0.01); the levels of CK, LDH, cTnT, IL-1β, and TNF-α in the serum of rats in the positive drug group and garlic freeze-dried powder high-dosage group decreased ( P<0.05 or P<0.01), while the expressions of p-PI3K, p-Akt, Nrf2, and HO-1 proteins in myocardial tissue increased ( P<0.05 or P<0.01), and the expression of Keap1 protein decreased ( P<0.05 or P<0.01). Conclusions:Garlic freeze-dried powder can improve acute myocardial ischemia of rats by reducing the release of serum myocardial enzymes and exerting antioxidant and anti-inflammatory effects. The mechanism may be related to regulating PI3K/Akt/Nrf2 signaling pathway.

Objective To evaluate the clinical efficacy of haloperidol combined with auricular point pressing therapy in children with tic disorders.Methods A total of 120 pediatric patients diagnosed with tic disorders at the Department of Pediatric Rehabilitation,Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Hebei Province from March 2022 to March 2024 were enrolled.Participants were randomly divided into an observation group(n=60)and a control group(n=60)using a random number table.The control group received haloperidol alone,while the observation group received additional auricular point pressing therapy.Treatment duration was 12 weeks.After 3 months,clinical efficacy was assessed by comparing:Yale Global Tic Severity Scale(YGTSS)scores,serum 5-hydroxytryptamine(5-HT)and dopamine(DA)levels,immune function markers(CD3+,CD4+),and incidence of adverse reactions between groups.Results(1)The overall efficacy rate in the observation group was 91.67％(55/60),while that in the control group was 76.67％(46/60).The efficacy of the observation group was superior to that of the control group,with a statistically significant difference(P＜0.05).(2)After treatment,the YGTSS scores of children in both groups was significantly improved(P＜0.05),and the observation group showed a significantly greater improvement in YGTSS scores than the control group,with a statistically significant difference(P＜0.05).(3)After treatment,the levels of 5-HT and DA in both groups of children were significantly improved(P＜0.05),and the observation group showed a significantly greater improvement in 5-HT and DA levels than the control group,with a statistically significant difference(P＜0.05).(4)After treatment,CD3+and CD4+levels were significantly improved in both groups(P＜0.05),and the observation group showed a significantly greater improvement in CD3+and CD4+levels than the control group,with a statistically significant difference(P＜0.05).(5)There was no statistically significant difference in the incidence of adverse reactions between the observation group and the control group,with a statistically significant difference(P＞0.05).Conclusion The combination of haloperidol and auricular point pressing therapy significantly improves clinical symptoms and immune function in children with tic disorders,demonstrating both efficacy and safety.