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.

Natural products (NPs) are an important source of new drugs for the treatment of stroke. Identifying cellular targets for bioactive molecules is a major challenge and critical issue in the development of new drugs for stroke. Small-molecule probes play a unique role in target discovery. However, drawbacks to these probes include non-specificity, unstable activity, and difficulty in synthesis. Small-molecule probes based on NPs at least partially compensate for these shortcomings. NPs feature rich chemical and structural diversity, biocompatibility, and unique biological activities. These features could be exploited to provide new ideas and tools for target discovery. Small-molecule probes based on NPs provide a precise and direct search for interacting protein targets of NPs-active small molecules. This review explores the properties of small-molecule probes based on NPs and their applications in mechanistic studies of stroke and other diseases. We hope that this review will bring new perspectives to the mechanistic study of NPs-active small molecules and accelerate the translation of these ingredients into drug candidates for the treatment of stroke.

Objective To explore the application effect of personalized osteotomy guide plate in high tibial osteotomy for patients with knee osteoarthritis(KOA).Methods A total of 99 patients with KOA who underwent open wedge high tibial osteotomy(OWHTO)in our hospital from January 2022 to January 2023 were selected and randomly divided into a study group(50 cases)and a control group(49 cases)using a random number table method.The control group received traditional medial OWHTO treatment,and the study group received a combination of medial OWHTO and personalized osteotomy guide plate treatment.The indexes of operation and postoperative rehabilitation,serum inflammatory stress factor[C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),cortisol(Cor),adrenocorticotropin(ACTH)],anatomical structure of knee joint[tibial plateau posterior Angle(PTSA),proximal medial tibial Angle(MPT A),hip knee ankle Angle(HKA)],knee function,ACL shape and function,postoperative complications were compared between the two groups.Results The amount of bleeding,the number of intraoperative fluoroscopy,and the postoperative drainage volume in the study group were(138.69±24.03)ml,(4.83±1.07)times,and(228.95±38.72)ml,respectively,which were all less than those in the control group(154.28±27.16)ml,(7.15±1.14)times,and(271.61±42.19)ml.In the study group,the operation time,incision length,and hospitalization time were(40.96±7.28)min,(8.96±0.85)cm,and(10.73±2.05)d,respectively,which were all shorter than those in the control group[(52.31±10.12)min,(9.51±1.03)cm,and(12.16±2.37)d],with statistically significant differences(P＜0.05).The levels of serum CRP,TNF-α,Cor,and ACTH in the study group on the 3rd day after the operation were(31.36±4.68)mg/L,(26.71±3.84)ng/ml,(241.28±27.45)ng/ml,and(18.65±3.01)pmol/L,respectively,which were lower than those in the control group[(35.07±5.16)mg/L,(30.29±4.15)ng/ml,(279.65±30.12)ng/ml,and(21.73±3.28)pmol/L,respectively],and the differences were statistically significant(P＜0.05).The Hospital for Special Surgery(HSS)knee score and Knee Society Score(KSS)of the study group at 12 months after surgery were(81.24±6.85)points and(78.26±6.14)points,respectively,which were higher than those of the control group[(78.08±6.42)points and(75.53±5.82)points,respectively],with statistically significant differences(P＜0.05);at the 12th month after surgery,the width of the ACL body in the study group was(5.68±0.71)mm,which was greater than that in the control group[(5.12±0.64)mm].The amount of anterior tibial displacement was(5.81±0.43)mm,which was smaller than that in the control group(6.19±0.41)mm,and the differences were statistically significant(P＜0.05);the incidence of postoperative complications in the study group was 4.00％,which was lower than that in the control group(18.37％),and the difference was statistically significant(P＜0.05).Conclusion The combined treatment of medial OWHTO and personalized osteotomy guide plate can reduce surgical trauma in patients with KOA,lower the incidence of complications,facilitate patient recovery,while maintaining the morphology and function of the ACL,and improving prognosis.

Anticoagulants are widely used in the prevention and treatment of thromboembolism.Existing anticoagulants share the common feature of antagonizing or blocking critical steps in the coagulation cascade,which also increases the risk of bleeding.Studies have indicated that factor Ⅺ inhibitors represent a potential therapeutic option for balancing thrombosis and bleeding risks.In recent years,various factor Ⅺ inhibitors,including antisense oligonucleotides(ASOs),monoclonal antibodies,synthetic small molecules,natural peptides,and aptamers,have been extensively researched as potentially exploitable anticoagu-lants.Research findings also suggest that factor Ⅺ inhibitors can reduce bleeding risks while ensuring anticoagulant efficacy,ex-hibiting potential for thrombosis prevention and treatment in patient populations such as those with end-stage renal disease,non-cardioembolic ischemic stroke,and acute coronary syndrome.This article reviewed the mechanisms of action,drug classes,pharma-cological characteristics,and clinical research progress of factor Ⅺ inhibitors,aiming to provide insights into the development of new anticoagulants and clinical anticoagulant therapies.

Objective To propose a novel method for immunohistochemically positive cell counting based on the improved YOLOv5s.Methods Regarding the small target characteristics of positive cells,a small target detection layer was added to refine feature extraction.Then,a bidirectional weighted feature pyramid network was used to replace path aggregation network(PANet)in the neck network for realizing multi-scale feature fusion.Additionally,the method used coordinate attention mechanism to make the model pay more attention to small target characteristics,and replaced the original GIoU with EIoU loss function for enhancing the detection performance.Results The model was trained on the self-built immunohistochemical image dataset.The average accuracy of the improved model was 89.3%,which was 4.0%higher than the original model and surpassed mainstream target detection models.The 5-year survival prediction model constructed with the method achieved an average accuracy of 76.8%and an average area under the curve of 0.81,demonstrating its superior prediction ability.Conclusion The proposed model can quickly detect the number of immunohistochemically positive cells and effectively assist doctors in survival prediction.

Objective To identify the taste critical quality attribute and design and optimize the flavor-correcting formulation of the traditional Chinese medicine oral preparation Qingre Jiedu Oral Liquid,in order to improve its taste and enhance patient medication adherence.Methods The taste assignment method was employed to identify the taste critical quality attribute of Qingre Jiedu Oral Liquid.Based on human sensory evaluation and the standardized Euclidean distance in electronic tongue analysis,suitable types of corrigent were determined.Subsequently,under constraints such as maximum allowable dosage,solubility,and sweetness,the optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined using Box-Behnken experimental design combined with electronic tongue and human sensory evaluation results.The study was reviewed and approved by the Ethics Committee of Beijing University of Chinese Medicine(Ethics Approval Number 2020BZYLL0609).Results The quantitative score for bitter taste of Qingre Jiedu Oral Liquid accounted for 30.36%,confirming bitterness as the taste critical quality attribute requiring attention.The optimal taste formulation for the sugar-free intermediate of Qingre Jiedu Oral Liquid was determined to be 120 mg·mL?1 erythritol,12 mg·mL?1 acesulfame potassium,and 2.4 mg·mL?1 stevioside.This formulation achieved an 11.75-point improvement in sensory evaluation scores compared to the original commercially available oral liquid.Conclusion This study successfully improved the taste of Qingre Jiedu Oral Liquid and established a comprehensive strategy for flavor-correcting formulation optimization,including a method for identifying taste critical quality attribute.This strategy provides a referential paradigm for palatability enhancement of similar traditional Chinese medicine oral preparations,laying a crucial technical foundation for elevating the clinical value of Chinese herbal medicines and promoting the high-quality development of traditional Chinese medicine(TCM).

Objective:To construct a scientific, systematic, and clinically applicable evaluation system of quality-sensitive indicators for nursing care of patients with tracheostomy and swallowing disorders following brain injury, providing a basis for evaluating nursing care quality in this patient population.Methods:By reviewing the literature and qualitative studies, a draft evaluation indicator was formed based on nursing issues related to patients with swallowing disorders during their hospital stay, employing the "structure-process-outcome" three-dimensional quality management model as the theoretical foundation. Between July and September 2023, two rounds of Delphi method expert consultations were conducted to add, delete, and modify indicators, and the analytic hierarchy process was used to determine indicator weights.Results:A total of 18 experts participated in two rounds of consultations, with a questionnaire return rate of 18/18. All 18 experts were female, with an average age of (47.61 ± 8.17) years. The expert authority coefficients were 0.895 and 0.910, while the Kendall concordance coefficients were 0.304 and 0.138 (all P<0.001). The average importance values assigned to each level of indicators ranged from 4.28 to 5.00. The final nursing evaluation indicators for patients with tracheostomy and swallowing disorders following brain injury included 4 first-level indicators, 21 second-level indicators, and 45 third-level indicators. Conclusions:By combining evidence-based research, current situation surveys, qualitative studies, and the Delphi method, a successful nursing quality evaluation indicator system was established for patients with tracheostomy and swallowing disorders following brain injury. These indicators are scientific, systematic, and clinically operable, playing an important role in improving the quality of nursing care for patients with tracheostomy and swallowing disorders following brain injury.

Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.

Objective:To explore the adaptability of health resources allocation and the economic development level in Sichuan Province and its influencing factors,so as to provide reference and suggestions for optimizing health resources allocation.Methods:Based on the panel data of 21 cities(states)in Sichuan Province,it analyzes the adaptability of health resources allocation and economic development in Sichuan Province from 2017 to 2021 and its influencing factors through entropy method,coupling coordination model and grey relational model.Results:From 2017 to 2021,the allocation level of health resources in most areas of Sichuan Province showed a gradual upward trend,but the rising speed was obviously lower than the growth rate of economic development;In 2021,the adaptability between the allocation of health resources and the level of economic development in most parts of Sichuan Province is still in a low coordination stage.Conclusion:Different regions should adopt differentiated development strategies based on their actual geographical conditions,optimize the allocation of health resources according to local conditions,and promote the coordinated development of health resource allocation and economic level.

Objective To investigate the acupoint selection law in acupuncture therapy for post-stroke respiratory dysfunction through data mining techniques with R language;To provide references for acupoint selection of clinical acupuncture practice for this disease.Methods Clinical research literature about acupuncture therapy for post-stroke respiratory dysfunction was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Cochrane Library,Web of Science and Embase from the establishment of the databases to February 20,2025.An acupuncture prescription database was established using Excel 2021.R 4.4.3 was used to analyze acupoint application frequency,meridian tropism,regional distribution and specific acupoints,and clustering analysis and association rule analysis were performed.Results Totally 123 articles were obtained,including 123 acupuncture prescriptions,involving 110 acupoints with a total application frequency of 723 times.High-frequency acupoints included Feishu(BL13),Hegu(LI4),Zusanli(ST36)and Fengchi(GB20),etc.The most frequently used meridians were the Bladder Meridian,Ren Meridian,Lung Meridian and Stomach Meridian.Acupoints were predominantly distributed in the head,neck and back regions,with crossing acupoints being the most commonly employed specific acupoints.Clustering analysis identified five meaningful acupoint combinations.The acupoint pair"Feishu(BL13)-Pishu(BL20)"demonstrated the strongest association.Conclusion Acupuncture treatment for post-stroke respiratory dysfunction follows the principle of strengthening the spleen to resolve phlegm and ventilating lung qi.The core acupoint combination is Feishu(BL13)-Pishu(BL20),with additional a acupoints adjusted based on syndrome differentiation to optimize therapeutic efficacy.