1.Electroacupuncture reduced airway inflammation by activating somatosensory-sympathetic pathways in allergic asthmatic rats.
Hongli MA ; Xiaowen LIU ; Huamei CAI ; Yun YAN ; Weixia LI ; Jing ZHAO
Chinese Medical Journal 2025;138(6):702-712
BACKGROUND:
Electroacupuncture (EA) treatment is efficacious in patients with respiratory disorders, although the mechanisms of its action in lung-function protection are poorly understood. This study aimed to explore the neuroanatomical mechanisms of EA stimulation at the BL13 acupoint (Feishu, EA-BL13) improvement in asthma.
METHODS:
Allergic asthma was induced by intranasal 2.0% ovalbumin (OVA) instillation combined with intraperitoneal injection of the 10.0% OVA. The levels of interleukin (IL)-4 and IL-5 were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin and periodic acid-schiff stain were used to evaluate inflammatory cell infiltration and mucus secretion. Cellular oncogene fos induction in neurons after EA stimulation was detected by immunofluorescent staining. The messenger RNA expression levels of adrenergic receptors were quantified with real-time polymerase chain reaction.
RESULTS:
EA improved airway inflammation and mucus secretion mainly by activating somatosensory-sympathetic pathways ( P <0.001). Briefly, the intermediolateral (IML) nuclei of the spinal cord received signals from somatic EA stimulation and then delivered the information via the sympathetic trunk to the lung. Excited sympathetic nerve endings in lung tissue released large amounts of catecholamines that specifically activated the β2 adrenergic receptor (β2AR) on T cells ( P <0.01) and further decreased the levels of IL-4 and IL-5 ( P <0.001) through the cyclic adenosine monophosphate/protein kinase A signaling pathway.
CONCLUSION
This study provided a new explanation and clinical basis for the use of EA-BL13 as a treatment for allergic asthma in both the attack and remission stages and other respiratory disorders related to airway inflammation.
Electroacupuncture/methods*
;
Animals
;
Asthma/immunology*
;
Rats
;
Rats, Sprague-Dawley
;
Male
;
Inflammation/therapy*
;
Interleukin-4/metabolism*
;
Interleukin-5/metabolism*
2.LncRNA SNHG15 promotes proliferation, migration and invasion of lung adenocarcinoma cells by regulating COX6B1 through sponge adsorption of miR-30b-3p.
Xiuying GONG ; Shunfu HOU ; Miaomiao ZHAO ; Xiaona WANG ; Zhihan ZHANG ; Qinghua LIU ; Chonggao YIN ; Hongli LI
Journal of Southern Medical University 2025;45(7):1498-1505
OBJECTIVES:
To explore the molecular mechanism by which lncRNA SNHG15 regulates proliferation, invasion and migration of lung adenocarcinoma cells.
METHODS:
The lncRNA microarray chip dataset GSE196584 and LncBase were used to predict the lncRNAs that interact with miR-30b-3p, and their association with patient prognosis were investigated using online databases, after which lncRNA nucleolar RNA host gene 15 (SNHG15) was selected for further analysis. The subcellular localization of lncRNA SNHG15 and its expression levels in normal human lung epithelial cells and lung adenocarcinoma cell lines were detected using fluorescence in situ hybridization and qRT-PCR. In cultured A549 cells, the changes in cell proliferation, migration, and invasion following transfection with a SNHG15 knockdown plasmid (sh-SNHG15), a miR-30b-3p inhibitor, or their co-transfection were assessed with EdU, wound healing, and Transwell assays. Bioinformatics analyses were used to predict the regulatory relationship between lncRNA SNHG15 and COX6B1, and the results were verified using Western blotting and rescue experiments in A549 cells transfected with sh-SNHG15, a COX6B1-overexpressing plasmid, or both.
RESULTS:
LncRNA SNHG15 was shown to target miR-30b-3p, and the former was highly expressed in lung adenocarcinoma, and associated with a poor patient prognosis. LncRNA SNHG15 was localized in the cytoplasm and expressed at higher levels in A549 and NCI-H1299 cells than in BEAS-2B cells. In A549 cells, lncRNA SNHG15 knockdown significantly inhibited cell migration, invasion and proliferation, and these changes were reversed by miR-30b-3p inhibitor. A regulatory relationship was found between lncRNA SNHG15 and COX6B1, and their expression levels were positively correlated (r=0.128, P=0.003). MiR-30b-3p knockdown obviously decreased COX6B1 expression in A549 cells, and COX6B1 overexpression rescued the cells from the inhibitory effects of lncRNA-SNHG15 knockdown.
CONCLUSIONS
LncRNA SNHG15 may compete with COX6B1 to bind miR-30b-3p through a ceRNA mechanism to affect proliferation, migration, and invasion of lung adenocarcinoma cells.
Humans
;
MicroRNAs/metabolism*
;
RNA, Long Noncoding/genetics*
;
Cell Proliferation
;
Cell Movement
;
Lung Neoplasms/genetics*
;
Adenocarcinoma of Lung
;
Neoplasm Invasiveness
;
A549 Cells
;
Adenocarcinoma/genetics*
;
Gene Expression Regulation, Neoplastic
;
Cell Line, Tumor
3.Relevant research on matrix metalloproteinases in the progression of pancreatic cancer
Hongli QIAO ; Zhanyu SONG ; Jianguo ZHAO
Chongqing Medicine 2025;54(5):1250-1254
The key to the growth and metastasis of pancreatic ductal adenocarcinoma(PDAC)is its complex stromal microenvironment and significant cellular and spatial heterogeneity.It can utilize the interac-tion between cellular and non cellular components in the microenvironment to induce immune escape and drug resistance,thereby reducing patient survival rates.In recent years,relevant studies have revealed the presence of non cellular components in the tumor microenvironment-matrix metalloproteinases(MMP),which can par-ticipate in inflammatory responses and cancer development by hydrolyzing the extracellular matrix.This arti-cle reviews the role of several MMP in the progression of pancreatic cancer,which have been confirmed by pre-vious studies.At the same time,MMP that may be associated with pancreatic cancer,but whose specific mech-anism has not yet been clarified are discussed in depth,providing a basic theoretical basis for further research on MMP as therapeutic targets for pancreatic cancer.
4.Retrospective epidemiological analysis of fungal infection of a hospital from 2018 to 2024
Zhihao LIU ; Yali LIU ; Lina GUO ; Yao WANG ; Ying ZHAO ; Xiuli XIE ; Wenjing LIU ; Renyuan ZHU ; Hongli SUN ; Hongtao DOU ; Dingding LI ; Lingli LIU ; Shuying YU ; Menglan ZHOU ; Qiwen YANG ; Yingchun XU ; Li ZHANG
International Journal of Laboratory Medicine 2025;46(21):2588-2594
Objective To analyze the main epidemiological characteristics of fungal infection in this hospital in the past 7 years,and to provide reference for clinical treatment and prevention and control strategies of fun-gal infection.Methods The fungal data and clinical data of related patients isolated from clinical samples in Peking Union Medical College Hospital from early January 2018 to the end of May 2024 were selected,and the main epidemiological characteristics of fungal infection in this hospital were identified and described through multi-angle statistical analysis.Results A total of 4 479 patients with filamentous fungal infection were en-rolled.The proportion of male patients[57.5%(2 576/4 479)]was higher than that of female patients[42.5%(1 903/4 143)],mainly distributed in internal medicine,Intensive Care Unit(ICU)and emergency de-partment,among which internal medicine accounted for the highest proportion[50.0%(2 241/4 479)].About 90.0%of the specimens were from the lower respiratory tract,in addition to specimens from skin and soft tis-sue,tissue,ear and blood culture.In terms of seasonal distribution,there are more patients in winter.The fun-gi were mainly composed of Aspergillus,Mucor,Cerdosporium,Fusarium and Penicillium,among which As-pergillus was the most abundant,accounting for 74.6%of the total.Aspergillus fumigatus was the most a-bundant Aspergillus,accounting for 42.5%of the total Aspergillus(1 418/3 340).Among the related infec-tions caused by mold,Aspergillus was the most common in the lower respiratory tract,accounting for 76.8%.Among them,Aspergillus fumigatus accounted for the highest proportion(33.6%).98.6%of the molds infected the ear were Aspergillus,of which Aspergillus niger and Aspergillus terreus were the most common.Skin infections are mainly caused by Sporothrix schenckii,Trichophyton rubrum,Microsporum ca-nis.The results of in vitro drug sensitivity test showed that the four common Aspergillus isolated in this hos-pital were sensitive to voriconazole,and amphotericin B had better antifungal activity against Mucorales in vitro.Conclusion Based on the main epidemiological characteristics of fungal infections in this hospital,it is recommended that special attention be paid to the admission of patients in the respiratory department during the peak infection period in autumn and winter.In the treatment of fungal infections in different regions and on different body parts,attention should be paid to the differences in the distribution of bacterial species.
5.Preparation of spermine-pullulan-PLGA-CD3 nanoparticles and their effects on T cell proliferation and cytokine secretion
Mengyuan WANG ; Hongyang CHEN ; Yifan HE ; Xi LI ; Mengyuan ZHAO ; Xiaocong DONG ; Yichen HE ; Hongli CHEN
International Journal of Biomedical Engineering 2025;48(1):33-40
Objective:To prepare pullulan-spermine (PS)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated with CD3 antibody, and to investigate their effects on T cell proliferation and cytokine secretion.Methods:Purulan polysaccharide was sperminized to synthesize PS, hydrophobically modified, and then grafted with PLGA to synthesize PS-PLGA. Infrared spectroscopy and nuclear magnetic resonance hydrogen spectrum were used to characterize the structure of PS-PLGA. PS-PLGA NPs were prepared by ultrasonic dialysis method and then coupled with CD3 antibody to prepare PS-PLGA-CD3 NPs. The morphological features of PS-PLGA-CD3 NPs were observed by the transmission electron microscope. The particle sizes, Zeta potential and dispersive coefficient of the NPs were measured using the dynamic laser particle size analyzer. The amount of coupled CD3 antibody on the surface of the NPs was determined using quantitative fluorescence analysis method. The effects of 1, 10, 50, 100, and 200 μg/ml PS-PLGA-CD3 NPs on T-cell proliferation were determined using cell counting kit-8 method. The effects of 1, 10, 50, 100, 200 μg/ml PS-PLGA-CD3 NPs on secretion of interferon-γ (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-β (TNF-β) by T cell were determined by enzyme-linked immunosorbent assay. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:Pullulan and PS showed strong absorption at 2 939 cm ?1, and PS had a weaker absorption peak at 3 384 cm ?1 than pullulan. The proton peaks of spermine appeared at chemical shifts of 1.25 to 1.50, 1.63, and 2.25 to 2.75. The characteristic peaks of PLGA appeared at chemical shifts of 1.50, 3.40, and 4.80 to 5.30. Compared to pullulan, the characteristic peaks of both PS and PLGA appeared in the corresponding intervals for PS-PLGA. The morphology of PS-PLGA-CD3 NPs with spermine substitution at 9.7% was all regular and circular, with a mean particle size of (173.3±24.5) nm, a Zeta potential of (?12.78±3.68) mV, the dispersive coefficient of 0.254±0.101, and the CD3 antibody mass fraction of (52.1±9.4) μg/mg. The differences in cell survival were statistically significant for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively, after co-incubation with T cell after 24, 48, and 72 h at concentrations of 50, 100, and 200 μg/ml, respectively (all P<0.05). The results of the three concentration comparisons after 24 h of co-incubation were [(129.8±23.1)% vs (95.5±8.9)%, (137.5±22.7)% vs (95.1±15.8)%, and (142.3±25.6)% vs (93.2±9.2)%]; and the results after 48 h were [(145.9±23.7)% vs (95.8±10.6)%, (149.3±23.5)% vs (94.9±16.3)%, and (161.2±26.9)% vs (91.5±8.3)%]; and the results after 72 h were [(147.6±20.1)% vs (95.9±17.8)%, (152.4±22.3)% vs (92.7±16.5)%, and (167.7±25.4)% vs (90.8±17.4)%]. The differences in the levels of IFN-γ, IL-2 and TNF-β were statistically significant (all P<0.05 or 0.01) at 50, 100 and 200 μg/ml concentrations for PS-PLGA-CD3 NPs and PS-PLGA NPs, respectively. For IFN-γ, the results of the comparison of the three concentrations were [(35.7±3.1) ng/ml vs (16.4±6.9) ng/ml, (67.3±5.2) ng/ml vs (19.6±2.8) ng/ml, and (79.0±4.2) ng/ml vs (19.3±2.3) ng/ml]; and for IL-2, the results were [(43.5±8.2) ng/ml vs (12.6±1.9) ng/ml, (53.5±7.8) ng/ml vs (15.8±3.3) ng/ml, and (64.0±8.2) ng/ml vs (17.4±3.8) ng/ml]; and for TNF-β, the results were [(108.4±18.9) pg/ml vs (40.8±1.3) pg/ml, (152.3±28.3) pg/ml vs (56.4±3.7) pg/ml and (185.0±33.6) pg/ml vs (81.6±10.2) pg/ml]. Conclusions:PS-PLGA-CD3 NPs are successfully prepared, which have the function of effectively promoting T cell proliferation and cytokine sectetion.
6.Evaluation of Risk Factors of Venous Thromboembolism in Patients Undergo-ing Gynecological Surgery and Establishment of a Modified Score Model
Xiaopeng ZHAO ; Danni LI ; Jun BAI ; Junyao CHEN ; Xinling TAN ; Hongli ZHU ; Lixiu LIU ; Nan LI ; Xiaoning LI ; Haijing WANG
Journal of Practical Obstetrics and Gynecology 2024;40(1):64-68
Objective:To study the risk factors of venous thromboembolism(VTE)and the predictive value of the improved VTE score model to identify the risk of VTE in gynecological surgery patients.Methods:From Janu-ary 1,2020 to December 31,2022,41 patients with VTE after gynecological surgery were selected as the VTE group,and a total of 164 patients with adjacent gynecological surgeries during the same period were selected as the non-VTE group with a ratio of 1 :4.Univariate and multivariate Logistic regression analysis were used to ana-lyze the risk factors of VTE after gynecological surgery,and a modified VTE risk factor rapid assessment model(referred to as the improved VTE score model)was constructed.The receiver operating characteristic(ROC)curve was used to study the predictive value for VTE for in gynecological surgery,and compared with the Caprini score model(Caprini table for short).Results:①Multivatiate Logistic regression analysis showed that there were independent risk factors for postoperative VTE in gynecology surgery(OR>1,P<0.05),including age≥60 years,BMI≥28 kg/m2,malignant tumors,surgery time>3 hours,history of thrombosis,and the increased D-di-mer difference before and after surgery.②The Area under Curve(AUC)of ROC was 0.963 in the improved VTE score model with a Youden index 81.10%,sensitivity 87.80%and specificity 93.29%.The AUC of the Caprini score model was 0.888 with Youden index 63.41%,sensitivity 73.17%and specificity 90.24%.The improved VTE score model the Caprini score model identified 92.68%and 85.37%of VTE patients as high-risk or ex-tremely high-risk,respectively,but the difference was not statistically significant(P<0.05).Conclusions:More attention should be paid to the six independent risk factors for postoperative VTE in gynecology surgery.The two score models showed a similar identified level.However,the improved VTE score model is more simple and easier to operate,has better practicality,and has certain clinical promotion value.
7.Arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint athrosis
Zhe ZHAO ; Hongli GENG ; Jianquan LIU ; Yongsheng LI ; Jianwen YIN ; Xiaoqiang CHEN ; Guanghui WANG ; Xiangyu CHENG ; Jiabei LI ; Zhiqin DENG ; Aozhengzheng DONG ; Manyi WANG ; Xiaofei ZHENG ; Wencui LI
Chinese Journal of Orthopaedics 2024;44(1):25-32
Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.
8.Correlation between grip strength promotion and improvement of body composition and metabolic disorders in health examination population of different genders
Yang WANG ; Wei ZHAO ; Hongli WANG ; Hua WU ; Jie GE ; Lei TIAN ; Na LIU ; Ying CHE ; Peng WANG
Chinese Journal of Health Management 2024;18(1):18-23
Objective:To explore the correlation between grip strength promotion and improvement of body composition and metabolic disorders in health examination population of different genders.Methods:In this retrospective cohort study, clinical data of 600 people who received health examination and grip strength check-up two times or more in the Medical Examination Center of Peking University Third Hospital from January 2018 to November 2022 were selected. The general data, physical examination, biochemical parameters, body composition and grip strength results were collected. After the first physical examination, the grip strength test was conducted, appropriate resistance strength exercises were given based on individual evaluation results. A health lecture was held, and the information related to health exercise was pushed through WeChat official account every week. The grip strength test was completed at the same time at the second physical examination, and the difference between the two test results was calculated before and after the second physical examination. The generalized estimation equation was used to analyze the correlation between the improvement of grip strength and the improvement of body composition and metabolic disorders in different gender health-check population.Results:In man and women, the body mass index [(25.50±3.66) vs (25.33±3.74) kg/m 2, (22.41±3.55) vs (22.25±3.46) kg/m 2] and grip strength [(42.71±7.30) vs (41.77±7.36) kg, (25.28±5.30) vs (23.98±4.87) kg] at the second health check-up were all significantly higher than those at the first time, and the diastolic blood pressure [(72.79±10.30) vs (74.47±9.85) mmHg (1 mmHg=0.133 kPa), (66.93±8.90) vs (68.92±9.42) mmHg] and serum homocysteine [(17.96±14.09) vs (19.27±14.26) μmol/L, (9.47±3.91) vs (10.26±3.90) μmol/L] were all significantly lower than those at the first time (all P<0.05). Among man, the low-density lipoprotein cholesterol (LDL-C) at the second physical examination was significantly lower than that at the first time [(2.94±0.78) vs (3.00±0.69) mmol/L] (all P<0.05). Among women, the systolic blood pressure and uric acid at the second health check-up were both significantly lower than those at the first time [(109.34±12.85) vs (110.54±12.32) mmHg, (276.91±62.46) vs (287.16±68.78) μmol/L], and the waist-hip ratio was significant higher (85.8%±5.1% vs 85.4%±5.0%) (all P<0.05). In males, the decreased aspartate aminotransferase ( OR=0.932, 95% CI: 0.888-0.978) and the increased skeletal muscle index ( OR=75.370, 95% CI: 29.012-195.806) were both positively correlated with the elevation of grip strength (all P<0.05); and in females, the decreased homocysteine ( OR=0.876, 95% CI: 0.782-0.982) and glycosylated hemoglobin ( OR=0.423, 95% CI: 0.222-0.805) and increased skeletal muscle index ( OR=22.918, 95% CI: 11.114-47.256) were all positively correlated with the elevation of grip strength (all P<0.05). Conclusion:There is a positive correlation between the improvement of grip strength and the improvement trend of body composition and metabolic disorders in in health examination population of different genders.
9.The value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening for non-small cell lung cancer: a meta-analysis
Honghai HE ; Huihui ZHANG ; Hua WU ; Hongli WANG ; Wei ZHAO ; Ping SUN ; Peng WANG
Chinese Journal of Health Management 2024;18(4):254-262
Objective:To evaluate the value of CEA, CYFRA21-1 and CA125 tests in opportunistic screening of non-small cell lung cancer (NSCLC) based on meta-analysis.Methods:The original research literatures on the diagnostic value of CEA, CYFRA21-1 and CA125 in Chinese NSCLC patients were searched from databases of PubMed, Embase, The Cochrane Library, CNKI, VIP, Database and Wanfang database from establishment to June 2023. The literature screening, data extraction and quality evaluation were carried out independently by two researchers. The quality evaluation tool of diagnostic accuracy studies was used to evaluate the quality of the literature. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the tests. The outcome stability and publication bias were detected by using sensitivity analysis and Deeks′ test.Results:A total of 23 studies met the inclusion and exclusion criteria were included. The results of meta-analysis showed that the overall sensitivity of CEA, CYFRA21-1 and CA125 alone in the diagnosis of NSCLC was relatively low, it was 0.49(95% CI: 0.43-0.55), 0.56(95% CI: 0.49-0.63) and 0.41(95% CI: 0.33-0.49), respectively. The overall sensitivity of the combined detection of the three markers for the diagnosis of NSCLC increased to 0.83(95% CI: 0.69-0.91), but the overall specificity decreased to 0.76(95% CI: 0.69-0.83). Conclusions:The single detection of CEA, CYFRA21-1 and CA125 is not recommended for screening NSCLC in population receiving physical examination. Although the sensitivity of the combined detection of CEA, CYFRA21-1 and CA125 for screening NSCLC is improved, but the specificity is decreased, the misdiagnosis rate is increased, so the screening effect is limited.
10.Molecular Mechanism of Endometrial Cell Senescence During Window of Implantation in Unexplained Recurrent Spontaneous Abortion and Intervention Effect of Bushen Huoxue Method
Xiaoxuan ZHAO ; Jing MA ; Xinyi DING ; Hongli ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):106-115
ObjectiveThis study aims to explore the molecular mechanism of endometrial cell senescence during the window of implantation (WOI) in unexplained recurrent spontaneous abortion (URSA) and the intervention effect of Bushen Huoxue method through the integrated research strategy of bioinformatics, machine learning, and animal experiments. MethodThe microarray gene sets of the endometrium of healthy women of childbearing age and patients with URSA during WOI were retrieved through the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) of URSA were screened by using the limma package of R language. Weighted gene co-expression network analysis (WGCNA) was used to obtain the most relevant module genes of URSA, and the gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. Gene sets related to cell senescence were obtained by the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The Venn online mapping software was used to screen the intersection genes of DEGs of URSA, the most relevant module genes, and the genes related to cell senescence. Then, the search tool for the retrieval of interacting genes/proteins (STRING) was used to analyze the protein-protein interaction (PPI) network of the interacting genes, and the hub genes were screened through Cytohubba. In addition, the least absolute selection and shrinkage operator (LASSO) and random forest algorithm were used to screen diagnostic genes related to cell senescence of URSA. Finally, mouse models with URSA were established and randomly divided into the model group, Bushen Huoxue group, and aspirin group, with six mice in each group, and six normal pregnant mice were selected as a blank group. The Bushen Huoxue group was given Shoutai pill combined with Danggui powder formula granular liquid (12.35 g·kg-1) by gavage, and the aspirin group was gavaged with aspirin at a dose of 0.011 mL·g-1. The blank group and model group were given the same volume of distilled water by gavage. Drug administration began on the first day after the discovery of vaginal thrombus (recorded as the first day of gestation, i.e. GD1), and the mice were sacrificed 12 hours after administration at GD5. The endometrium samples were collected. Quantitative real-time polymerase chain reaction (Real-time PCR) and immunofluorescence were used to detect the expression of cell senescence-related diagnostic genes in the endometrium tissue of URSA mice during WOI and the intervention effect of the Bushen Huoxue method. ResultThe gene set of the GSE165004 microarray was included for bioinformatics analysis. According to the “limma” package of R language, 585 DEGs of URSA were selected (P<0.05). WGCNA results suggested that the gene in the magenta module was the most closely related to URSA (r=0.32, P<0.05). The results of the KEGG analysis of the magenta module suggested that the genes were mainly enriched in cell senescence, Hippo, and NF-κB signaling pathways (P<0.05). In addition, 2 138 genes related to cell senescence were obtained from Genecards and OMIM websites. The Venn online mapping tool was used to obtain 27 intersecting genes of DEGs of URSA, the magenta module genes, and cell senescence-related genes, namely, cell senescence-related DEGs in endometrium tissue during WOI of URSA. PPI analysis showed that synuclein alpha (SNCA), heme oxygenase 1 (HOMX1), and matrix metallopeptidase 1 (MMP1) were hub genes. Besides, four diagnostic genes were identified by LASSO regression and random forest, including gelsolin (GSN), cyclin2 (CCND2), RB binding protein 8 (RBBP8), and lysophosphatidic acid receptor 1 (LPAR1). Animal experiments confirmed that the mRNA level and fluorescence intensity of GSN were significantly increased (P<0.05), while the mRNA and fluorescence intensity of CCND2, LPAR1, and RBBP8 were significantly decreased (P<0.05) in the model group when compared with the blank group. The expression level of GSN was decreased (P<0.05), while the expression levels of CCND2, LPAR1, and RBBP8 were remarkably increased (P<0.05) in the Bushen Huoxue group when compared with the model group. ConclusionThe senescence of endometrial cells during WOI of URSA is related to multiple genes. Bushen Huoxue method can act on multiple targets that are related to cell senescence, which may be the key mechanism of improving endometrial receptivity in URSA.

Result Analysis
Print
Save
E-mail