Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*

Objective To investigate the size variation in the first metatarsal of extant primates.Methods In this study,we analyzed 135 first metatarsal specimens across 12 primate genera,quantifying eight linear measurements,articular surface areas,mid-shaft cross-sectional area,total surface area,volume,and derived indices.Multivariate patterns were assessed through mean-based correspondence analysis and principal component analysis(PCA).Results Eulemur,Otolemur,Cebus,and Perodicticus exhibited a relatively high metatarsal surface-area-to-volume ratio.Perodicticus additionally showed a low articular facet index.Propithecus,Colobus,and Macaca displayed lower values for metatarsal shaft robusticity,the ratio of shaft cross-sectional area to base articular surface area,and the proximal articular facet index.Nasalis possessed a relatively high articular facet index.Pongo,Pan,Gorilla,and Homo sapiens were characterized by higher metatarsal shaft robusticity and a lower metatarsal surface-area-to-volume ratio.Principal component analysis revealed that the 12 extant primate genera could be broadly divided into two groups.Group 1 comprised Pongo,Pan,Gorilla and H.sapiens,although H.sapiens formed a distinct cluster relative to the extant great apes.Group 2 included Eulemur,Otolemur,Perodicticus,Propithecus,Cebus,Colobus,Macaca and Nasalis.Conclusion The relative sizedistribution of the first metatarsal provides some reference value for classifying extant primates.However,it demonstrates no clear correlations with specific locomotor patterns or foot grasping ability.

Objective To investigate the effects of oxymatrine on proliferation and apoptosis of diffuse large B-cell lymphoma and its molecular mechanism.Methods Human diffuse large B lymphoma cells OCI-LY19 were randomly divided into control group(normal culture),experimental-L group(25.00 μmol·L-1 oxymatrine),experimental-M group(50.00 μmol·L-1 oxymatrine),experimental-H group(100.00 μmol·L-1 oxymatrine),Oxymatrine+si-NC group(transfected with si-NC+100.00 μmol·L-1oxymatrine),Oxymatrine+si-PD-L1 group[transfected with si-programmed death receptor ligand 1(PD-L1)+100.00 μmol·L-1 oxymatrine],Oxymatrine+Vector group(transfected with si-NC+100.00 μmol·L-1 oxymatrine)and oxymatrine+PD-L1 group(transfected with PD-L1+100.00 μmol·L-1 oxymatrine).5-acetylidene-2'-deoxyuridine(EdU)assay was used to detect cell proliferation;Western blot assay was used to detect protein expression;flow cytometry assay was used to detect cell apoptosis.Results The EdU cell proliferation rates in control group,experimental-H group,oxymatrine+si-NC group,oxymatrine+si-PD-L1 group,oxymatrine+Vector group and oxymatrine+PD-L1 group were(33.88±2.79)％,(15.23±1.32)％,(15.84±1.58)％,(10.13±0.90)％,(16.14±1.20)％and(20.84±1.88)％,respectively;the expressions of Cyclin-dependent kinase 4(CDK4)protein were 0.92±0.11,0.37±0.04,0.35±0.04,0.24±0.03,0.38±0.06 and 0.71±0.06,respectively;the apoptosis rates were(3.20±0.07)％,(25.35±2.01)％,(24.81±1.91)％,(30.27±1.65)％,(24.39±2.73)％and(17.97±1.27)％,respectively.The above indicators:Experimental-H group were compared with the control group respectively,and the differences were statistically significant(all P＜0.05);there were significant differences between oxymatrine+si-PD-L1 group and oxymatrine+si-NC group(all P＜0.05);there were significant differences between oxymatrine+PD-L1 group and oxymatrine+Vector group(all P＜0.05).Conclusion Oxymatrine can inhibit the proliferation of OCI-LY19 cells and induce apoptosis by down-regulating the expression of PD-L1.PD-L1 may be a potential target of oxymatrine in the treatment of diffuse large B lymphoma.

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.

Objective To design a portable intelligent cleaner for medical lumen instruments to enhance cleaning efficiency.Methods The portable intelligent cleaner had a box-body shape and a shell made of 304 stainless steel,which was composed of a circuit control board,a micro pump,lithium batteries,a charging interface,a rinse tube and connectors.The circuit control board used a STM32G030C8T6 integraged circuit,which was equipped with a countdown digital tube to display the time left for cleaning;the micro pump and lithium batteries were placed at the inner wall of the box bottom,the charging interface and water inlet/outlet inteface were put on the outside of the front wall of the box bottom,the water inlet/outlet interface was connected with a silicon rinse tube linked to an adapter at its distal end,and the adapters with different calibers were compatible with sizes of medical lumen instruments.Totally 9 672 pieces of lumen instruments received by some hospital's disinfection supply center from May to October 2021 were divided into 2 groups with the convenience sampling method,with 4 836 pieces in each group.The odd-numbered instruments were enrolled into a control group and cleaned with an ultrasonic cleaner and a lumen brush,and the even-numbered instruments were included into an experimental group and cleaned conventionally after pretreatment by the intelligent cleaner.The two groups were compared in terms of eaning efficiency and satisfaction.Results Testing by visual inspection,magnifying glass with light source and white stripe method showed that the experimental group behaved better than the control group in the cleaning qualification rate,whose satisfaction rate(100％)was also higher than that of the control group(86.53％),with all the differences being statistically significant(P＜0.05).Conclusion The portable cleaner with easy operation enhances the cleaning quality and efficiency for medical lumen instruments.[Chinese Medical Equipment Journal,2024,45(10):114-117]

Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

The aim of this study is to analyze the research hotspots and development trends in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022. Based on China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Science and Technology Journal Database, China Biology Medicine disc, Web of Science core collection and PubMed database, the related literatures in the field of pathogenesis of diabetic nephropathy in China from 2013 to 2022, were retrieved to establish the database, and the VOSviewer software was used for bibliometric analysis. A total of 1 664 Chinese and 2 149 English literatures are included in this study. The scientific research results from 2013 to 2022 have shown an overall increasing trend. The research hotspots in the field of pathogenesis of diabetic nephropathy in China are mainly concentrated in Podocytes, Oxidative stress, Inflammation, Renal fibrosis, Urine protein, etc. The frontier hotspots in this field include Biomarkers, Nrf2, Gut microbiota, NLRP3 inflammasome, Apoptosis, MicroRNA, etc. Through visual analysis, the research hotspots and frontier trends of the pathogenesis of diabetic nephropathy in China can be visually presented, and then provide new ideas and directions for the further in-depth research on the pathogenesis of diabetic nephropathy.
Humans ; Apoptosis ; Asian People ; China/epidemiology* ; Diabetes Mellitus ; Diabetic Nephropathies/etiology* ; MicroRNAs ; Biomedical Research/trends*

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.
Humans ; Infant ; Gene Expression Profiling ; Sudden Infant Death/genetics* ; Gene Regulatory Networks ; Protein Interaction Maps/genetics* ; Computational Biology

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-