1.Application of a dynamic urine output‑guided intermittent catheterization protocol in bladder safety management for patients with neurogenic bladder
Liangxiang REN ; Yun YANG ; Rong CAO ; Wei ZHANG ; Yiqing YE ; Qianxia NIU ; Tao JIANG ; Peipei MEI
Chinese Journal of Rehabilitation Theory and Practice 2026;32(8):978-983
ObjectiveTo explore the effect of individualized intermittent catheterization (IC) guided by 24-hour dynamic urine volume monitoring on bladder function and urinary tract infection complications in patients with neurogenic bladder (NB). MethodsA total of 50 NB patients admitted to the First Affiliated Hospital of Nanjing Medical University from August, 2025 to June, 2026 were enrolled. The patients were randomly divided into control group (n = 25) and experimental group (n = 25). The control group received routine timed/empirical IC, and the experimental group adopted dynamic urine volume-guided individualized IC, for a week. Urine leukocyte positive rate, urine bacterial positive rate, frequencies of single catheterized volume > 400 mL, 24-hour catheterization and 24-hour urine leakage were recorded before and after intervention. ResultsAfter intervention, the positive rates of urine leukocytes and urine bacteria were lower in the experimental group than in the control group (χ2 > 5.094, P < 0.05), while the frequencies of single catheterized volume > 400 mL, 24-hour catheterization and 24-hour urine leakage were less (t > 2.078, P < 0.05). ConclusionThe individualized IC guided by 24-hour dynamic urine volume monitoring can accurately match individual urine secretion rhythm, reduce over-distension of bladder and unnecessary catheterization, and lower the incidence of urine leakage and urinary tract infection.
2.Current Situation, Problems and Countermeasures of Experimental Research on Traditional Chinese Medicine Regulating PI3K/Akt Signaling Pathway in Rats with Polycystic Ovary Syndrome
Pengxuan YAN ; Yiqing LIU ; Nanxing XIAN ; Linjing PENG ; Kun LI ; Jingchun ZHANG ; Yukun ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):259-266
Polycystic ovary syndrome(PCOS) and its resulting infertility is one of the common diseases of gynecology and reproductive endocrinology. The phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathway is relatively well-studied in the development of intervention in PCOS, and the experiments on PCOS in rats conducted by traditional Chinese medicine through this signaling pathway is also the main direction of mechanistic research. In this paper, 20 articles published in academic journals in the past 5 years were selected through the corresponding criteria, and the objective situation and existing problems of the selected research projects were analyzed from five aspects, namely, baseline data, modeling and treatment, grouping, evaluative indexes, and pharmacodynamic indexes. It is found that there were different degrees of problems in each research project, such as the observation indicators of modeling, criteria for judging the success of the model, the treatment period, the calculation of dosage of prescription/active ingredients and specific dosage were not clearly defined, which could easily lead the bias of the results or reduce the validity of experimental data. Based on this, the list of PCOS rat experimental research operations was formed, involving five categories of experimental rats, model construction, study implementation, outcome measures and analysis and report with a total of 21 operation lists, with a view to provide a reference for the subsequent PCOS experiments related to scientific research and helping to form high-quality results.
3.Analyzing the relationship between occupational stress and radiation protection knowledge-attitude-practice among radiation workers
Huiyu HOU ; Yue JIANG ; Dingqi JIAO ; Yiqing TIAN ; Huaxing ZHANG
China Occupational Medicine 2025;52(1):61-65
Objective To explore the influence of radiation protection knowledge-attitude-practice (RP-KAP) on occupational stress of radiation workers. Methods A total of 314 radiation workers from five hospitals in Shijiazhuang City were selected as the study subjects using the convenient sampling method. The Chinese version of the "Effort-Reward Imbalance (ERI) Questionnaire" and the "Radiation Protection Knowledge, Attitude, and Practice Questionnaire" were used for investigation. Results The detection rate of occupational stress in ERI model among the radiation workers was 74.5% (234/314). The RP-KAP practice dimension score of the population in the occupational stress group was lower than that in the non-occupational stress group (P<0.05). The results of binary logistic regression analysis showed that radiation workers with lower RP-KAP practice dimension score had a higher risk of occupational stress (P<0.01), and the risks of occupational stress among population of interventional radiology group and radiotherapy group were higher than that of X-ray diagnosis group and nuclear medicine group (both P<0.05), after controlling for confounding factors such as gender, age, type of work, professional title, daily working hours, weekly working hours and regular vacation. Conclusion RP-KAP is the influencing factor of occupational stress in the radiation workers. To improve the radiation workers' knowledge of radiation protection, protection awareness and compliance with protective behavior can effectively reduce or even eliminate occupational stress.
4.Role of spinal Annexin A3 in neuropathic pain in mice
Zengli ZHANG ; Qian PAN ; Ruichen SHU ; Zhenguo SONG ; Yiqing YIN
Chinese Journal of Anesthesiology 2025;45(3):335-340
Objective:To evaluate the role of spinal Annexin A3 (ANXA3) in neuropathic pain in mice.Methods:Sixty-four SPF healthy adult male C57BL/6 mice, weighing 22-26 g, aged 8-10 weeks, were divided into 4 groups ( n=16 each) by the random number table method: sham operation group (group S), chronic constriction injury (CCI) group, CCI+ negative control adeno-associated virus AAV-NC group (group CCI+ N) and CCI+ adeno-associated virus AAV-shANXA3 group (group CCI+ sh). The neuropathic pain was induced by CCI of the sciatic nerve in anesthetized animals. The AAV-shANXA3 and AAV-NC (5 μl) were intrathecally injected at 14 days before developing the model in CCI+ N group and CCI+ sh group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before developing the model and at 7, 14 and 21 days after developing the model. All the mice were sacrificed after the last measurement of pain threshold, the L 4-6 segments of the spinal cord were removed for determination of the expression of ANXA3, phosphorylated nuclear factor-kappa B (p-NF-κB) and ionized calcium-binding adaptor molecule-1 (Iba-1)(by Western blot), expression of ANXA3 mRNA (by real-time polymerase chain reaction), microglial activation (using the immunofluorescence staining), and contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 and anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and IL-10 (using enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased and TWL was shortened after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 in spinal cord was up-regulated, the contents of TNF-α, IL-1β and IL-6 were increased, the contents of TGF-β and IL-10 were decreased ( P<0.05), the activation of microglia in the spinal cord was significantly increased, and the cell body was enlarged in group CCI. There was no significant difference in each parameter between group CCI and group CCI+ N ( P>0.05). Compared with CCI+ N group, the MWT was significantly increased on days 14 and 21 after developing the model, the TWL was prolonged on day 21 after developing the model, the expression of ANXA3 protein and mRNA, p-NF-κB and Iba-1 was down-regulated, the contents of TNF-α, IL-1β and IL-6 were decreased, the contents of TGF-β and IL-10 were increased ( P<0.05), and the activation of spinal microglia was decreased in CCI+ sh group. Conclusions:Spinal ANXA3 may be involved in the development and maintenance of neuropathic pain by activating the NF-κB signaling pathway and further promoting microglial activation in mice.
5.Research on the construction and application of a communication skills assessment scale for newly employed nurses
Yiqing LIU ; Yin ZHANG ; Minjie QIAN ; Yimin QIU ; Jing ZHANG ; Ting ZHANG ; Jiequn YANG ; Jiayu WANG
Chinese Journal of Medical Education Research 2025;24(7):878-884
Objective:To construct a communication skills assessment scale for newly employed nurses, verify the reliability and validity of the scale in a simulated setting, and develop and construct an effective and structured assessment tool for the communication skills of newly employed nurses.Methods:The Chinese version of the Liverpool Communication Skills Assessment Scale was modified and two rounds of expert consultation were conducted to construct the communication skills assessment scale for newly employed nurses. A total of 194 newly employed nurses at a tertiary hospital between 2024 and 2025 were selected using convenience sampling. Data were collected using a teacher-based evaluation method during simulated communication scenarios. The performance of the nurses was scored, and the reliability and validity of the scale were analyzed.Results:The final version of the scale consisted of 4 dimensions and 11 items, and can be used in both workplace-based and simulation-based evaluations. The expert authority coefficients of both rounds were greater than 0.70. The Kendall's W coordination coefficients for the two rounds of consultation were 0.278 and 0.309 for workplace-based evaluations and 0.256 and 0.295 for simulation-based evaluations. The coefficients of variation for the 11 items in both application scenarios were <0.250. The total Cronbach's alpha coefficient of the scale was 0.805 and the total split-half reliability coefficient was 0.814. In the two application scenarios, the item-level content validity index ranged from 0.769 to 1.000 (all >0.750). The scale-level content validity index was 0.916 and 0.909 (>0.900), respectively, in the workplace-based and simulation-based evaluations. The exploratory factor analysis extracted a total of four common factors, with a cumulative variance contribution of 69.09%, and all item loadings on their corresponding factors exceeded 0.500. Conclusions:The communication skills assessment scale for newly employed nurses has moderate and validated content and number of items. The scale demonstrates high reliability and validity in simulation-based evaluations, and can be used as an effective tool for assessing the communication skills of newly employed nurses.
6.Role of"HA coat"in modulating stemness and endocrine resistance in ER+breast cancer
Shiyi WU ; Si CHEN ; Bohan LIU ; Yuting LIU ; Yiwen LIU ; Yiqing HE ; Yan DU ; Guoliang ZHANG ; Qian GUO ; Feng GAO ; Cuixia YANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(10):1298-1307
Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.
7.Medication regularity and mechanism of prescriptions containingtraditional Chi-nese medicine compound formulas in treatment of sepsis based on data mining and network pharmacology
Lin DU ; Weidong HU ; Hanlin ZHOU ; Wanqin LUO ; Xiyao TANG ; Yiqing WANG ; Yin LI ; Li ZHANG ; Jun LI ; Liting CAO ; Shicheng BI
Chinese Journal of Veterinary Science 2025;45(4):782-793
This study aims to investigate the medication rules of patented traditional Chinese medi-cine(TCM)compound formulas and molecular mechanisms of core drugs for treating sepsis using data mining and network pharmacology approaches.In the present study,we first searched the PubMed database,Web of Science database,and the China National Knowledge Infrastructure(CNKI)since the establishment of the library to April 30,2024 for the relevant literature on the treatment of sepsis by traditional Chinese medicine.The prescriptions were then statistically ana-lyzed for drug frequency and association analysis to obtain the core drugs.Then we screened the ef-fective active ingredients of the core drugs by TCMSP and other database platforms,obtained sep-sis-related genes in GeneCards and other databases,and statistically intersected targets,and predic-ted the mechanism of action of the core TCMs by subjecting the intersected targets to PPI analy-sis,GO function and KEGG pathway enrichment analysis.Finally,the relationship between key tar-gets and herbal components was examined in reverse by molecular docking method.The results showed that 64 compound formulas were obtained,with a total of 150 Chinese medicines,which were mostly sweet in taste,cold in nature,and belonged to the spleen,stomach and intestinal me-ridians.According to the association rules,the core drugs were identified as"mirabilite-peach ker-nel-rheum officinale".There were 79 intersecting targets between the core drugs and sepsis,with core targets such as IL-1β,EGFR and SRC.MAPK,TNF,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert ther-apeutic effects on sepsis.The molecular docking results indicated that the docking activity of the key targets with the main components of the drug,and sennoside E_qt has the lowest binding ener-gy and the best docking activity with SRC.In conclusion,this study showed that the prescription of Chinese medicine for sepsis is mostly based on tonifying the spleen and clearing heat.The mecha-nism of action of the core drug"mirabilite-peach kernel-rheum officinale"in the treatment of sep-sis is multilevel and multifaceted,which provides a certain theoretical basis for the treatment of sepsis by traditional Chinese medicine.
8.Protective effect of hydrogen on septic mice acute lung injury by regulating store-operated Ca 2+ entry induced by STIM1/Orai1
Yuan LI ; Ruichen SHU ; Xiaobei ZHANG ; Yiqing YIN
Chinese Critical Care Medicine 2025;37(5):438-444
Objective:To investigate the effect of hydrogen on the expressions of stromal interaction molecule 1 (STIM1) and Ca 2+-release-activated-Ca 2+ channel protein 1 (Orai1) and the protective effect of hydrogen on septic mice acute lung injury (ALI). Methods:Forty-eight male ICR mice were divided into sham operation group (Sham group), hydrogen control group (Sham+H 2 group), sepsis group (SS group) and hydrogen intervention group (SS+H 2 group) according to a random number table method, with 12 mice in each group. Sepsis mice model were established by cecal ligation and puncture (CLP). Sham group and Sham+H 2 group did not undergo CLP, other operations were the same as follow. Sham+H 2 group and SS+H 2 group received 1 hour inhalation of 2% H 2 at 1 hour and 6 hours after CLP or sham operation. At 24 hours after CLP, 6 mice in each group were sacrificed for observing pulmonary microvascular permeability after injecting Evans blue (EB) through tail vein. Other 6 mice in each group were sacrificed for obtaining fresh lung tissue to observe the lung pathological change and lung wet/dry (W/D) weight ratio. The protein expressions and distribution of STIM1 and Orai1 in lung tissue were detected by Western blotting and immunofluorescence staining. The mRNA expressions of STIM1 and Orai1 in lung tissue were detected by reverse transcriotion-polymerase chain reaction (RT-PCR). Coimmunoprecipitation was used to observe STIM1-Orai1 interaction. Finally, pulmonary microvascular endothelial cells (PMVEC) of mice were cultured in vitro and randomly divided into four groups for inoculation onto culture plates: Control group, rich hydrogen solution group (Control+H 2 group), lipopolysaccharide (LPS) group and rich hydrogen solution intervention group (LPS+H 2 group). PMVECs in Control group and LPS group were cultured in normal medium. Control+H 2 group and LPS+H 2 group were cultured in saturated hydrogen medium. LPS group and LPS+H 2 group were added with LPS at 5 μg/mL. Intracellular Ca 2+ ([Ca 2+]i) concentration of PMVECs were detected by Fluo-4/AM green dye. Results:Compared with Sham group, the pathological score and lung W/D ratio were significantly increased in SS group at 24 hours after CLP (pathological score: 11.00±1.41 vs. 1.00±0.63, lung W/D ratio: 7.63±0.52 vs. 3.45±0.58, both P < 0.05), the content of EB in the lung tissue was increased (μg/g: 0.16±0.02 vs. 0.09±0.02, P < 0.05). Compared with SS group, the pathological score and lung W/D ratio were decreased in SS+H 2 group (pathological score: 3.50±1.05 vs. 11.00±1.41, lung W/D ratio: 4.45±0.45 vs. 7.63±0.52, both P < 0.05), the content of EB in the lung tissue was decreased (μg/g: 0.13±0.02 vs. 0.16±0.02, P < 0.05), which prove that hydrogen can improve ALI caused by sepsis. Compared with Sham group, the protein and mRNA expressions of STIM1 and Orai1 were up-regulated in SS group (relative expression level of STIM1 protein: 3.08±0.32 vs. 1.00±0.00, relative expression level of STIM1 mRNA: 3.65±0.24 vs. 1.00±0.00, relative expression level of Orai1 protein: 3.63±0.23 vs. 1.00±0.00, relative expression level of Orai1 mRNA: 3.80±0.22 vs. 1.00±0.00, all P < 0.05), while the protein and mRNA expressions of STIM1 and Orai1 were down-regulated in SS+H 2 group compared with SS group (relative expression level of STIM1 protein: 1.78±0.13 vs. 3.08±0.32, relative expression level of STIM1 mRNA: 1.76±0.28 vs. 3.65±0.24, relative expression level of Orai1 protein: 1.92±0.22 vs. 3.63±0.23, relative expression level of Orai1 mRNA: 1.85±0.18 vs. 3.80±0.22, all P < 0.05). Coimmunoprecipitation staining results showed that there was no statistically significance in the association between STIM1 and Orai1 in Sham group and Sham+H 2 group. Compared with Sham group, the STIM1-Orai1 interaction was increased in SS group (relative expression level: 3.71±0.37 vs. 1.00±0.00, P < 0.05), while the STIM1-Orai1 interaction was decreased in SS+H 2 group compared with SS group (relative expression level: 2.17±0.29 vs. 3.71±0.37, P < 0.05). There were no statistically significant differences in various indicators between Sham group and Sham+H 2 group. In vitro, the intracellular [Ca 2+]i concentration in PMVECs was increased in LPS group compared with Control group using Fluo-4/AM green dye. The intracellular [Ca 2+]i concentration in PMVECs was decreased in LPS+H 2 group compared with LPS group. Conclusion:The protective effect of hydrogen on lung tissues in septic mice is related to the inhibition of STIM1, Orai1 and the interaction between them.
9.Mechanism of Kidney-tonifying and Liver-regulating Cyclical Therapy and Formula in Improving Endometrial Receptivity during "Implantation Window" in Rats with Polycystic Ovary Syndrome via miR-140-5p/VEGF Pathway
Quan LIU ; Yiqing HE ; Ying ZHANG ; Xi WANG ; Shuo YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):100-109
ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome (PCOS). MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group, and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method, the rats were divided into the following groups: normal group, model group, Xiaoyaosan group (11.97 g·kg-1), Sanzi Yangmo decoction group (28.35 g·kg-1), cyclical therapy group (11.97/28.35 g·kg-1), and aspirin group (8 × 10-3 mg·kg-1). After 12 days of continuous administration by gavage (equivalent to three estrous cycles), female and male rats were co-housed. On the fifth day of pregnancy, the number of blastocyst implantation in each group was counted. Hematoxylin-eosin (HE) staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of estradiol (E2) and progesterone (P) in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor (VEGF), progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), and integrin(ITG) αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-140-5 P, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), PR, ER, AR, and ITGαvβ3 in rat endometrium. ResultsCompared with normal group, the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner, the number of uterine glands and blood vessels were significantly reduced (P<0.01), and the pregnancy rate was significantly reduced. Compared with the model group, each drug group restored the regular estrous cycle to varying degrees, and the endometrial thickness and the number of blood vessels were significantly improved (P<0.01). The pregnancy rate of each drug group increased, and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group, the levels of serum E2 and P in the model group were significantly decreased (P<0.01), the expression of VEGF, ER, PR and ITGαvβ3 protein was significantly decreased (P<0.05,P<0.01), the expression of AR protein was significantly increased (P<0.01), the expression of miR-140-5P and AR mRNA was significantly increased (P<0.01), and the expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA was significantly decreased (P<0.01). Compared with model group, the serum E2 level in the Xiaoyaosan group was significantly increased (P<0.01).The levels of E2 and P in serum of rats in Sanzi Yangmo decoction group, cycle therapy group and aspirin group were significantly increased (P<0.01). The expression of AR protein in each drug group was significantly decreased (P<0.01). The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased (P<0.01). The expression of VEGF, ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees (P<0.05,P<0.01). The expression of VEGF, PR, ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees (P<0.05,P<0.01). The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased (P<0.01). The expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA in each drug group increased to varying degrees (P<0.05,P<0.01). Compared with Xiaoyaosan group and Sanzi Yangmo decoction group, the expression of miR-140-5P, VEGFR2, ER, PR, AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different (P<0.05,P<0.01). ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P, target the upregulation of VEGF expression, mediate angiogenesis, and promote endometrial angiogenesis, thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.
10.Mechanism of Kidney-tonifying and Liver-regulating Cyclical Therapy and Formula in Improving Endometrial Receptivity during "Implantation Window" in Rats with Polycystic Ovary Syndrome via miR-140-5p/VEGF Pathway
Quan LIU ; Yiqing HE ; Ying ZHANG ; Xi WANG ; Shuo YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):100-109
ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome (PCOS). MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group, and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method, the rats were divided into the following groups: normal group, model group, Xiaoyaosan group (11.97 g·kg-1), Sanzi Yangmo decoction group (28.35 g·kg-1), cyclical therapy group (11.97/28.35 g·kg-1), and aspirin group (8 × 10-3 mg·kg-1). After 12 days of continuous administration by gavage (equivalent to three estrous cycles), female and male rats were co-housed. On the fifth day of pregnancy, the number of blastocyst implantation in each group was counted. Hematoxylin-eosin (HE) staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of estradiol (E2) and progesterone (P) in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor (VEGF), progesterone receptor (PR), estrogen receptor (ER), androgen receptor (AR), and integrin(ITG) αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-140-5 P, VEGF, vascular endothelial growth factor receptor 2 (VEGFR2), PR, ER, AR, and ITGαvβ3 in rat endometrium. ResultsCompared with normal group, the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner, the number of uterine glands and blood vessels were significantly reduced (P<0.01), and the pregnancy rate was significantly reduced. Compared with the model group, each drug group restored the regular estrous cycle to varying degrees, and the endometrial thickness and the number of blood vessels were significantly improved (P<0.01). The pregnancy rate of each drug group increased, and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group, the levels of serum E2 and P in the model group were significantly decreased (P<0.01), the expression of VEGF, ER, PR and ITGαvβ3 protein was significantly decreased (P<0.05,P<0.01), the expression of AR protein was significantly increased (P<0.01), the expression of miR-140-5P and AR mRNA was significantly increased (P<0.01), and the expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA was significantly decreased (P<0.01). Compared with model group, the serum E2 level in the Xiaoyaosan group was significantly increased (P<0.01).The levels of E2 and P in serum of rats in Sanzi Yangmo decoction group, cycle therapy group and aspirin group were significantly increased (P<0.01). The expression of AR protein in each drug group was significantly decreased (P<0.01). The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased (P<0.01). The expression of VEGF, ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees (P<0.05,P<0.01). The expression of VEGF, PR, ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees (P<0.05,P<0.01). The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased (P<0.01). The expression of VEGF, VEGFR2, ER, PR and ITGαvβ3 mRNA in each drug group increased to varying degrees (P<0.05,P<0.01). Compared with Xiaoyaosan group and Sanzi Yangmo decoction group, the expression of miR-140-5P, VEGFR2, ER, PR, AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different (P<0.05,P<0.01). ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P, target the upregulation of VEGF expression, mediate angiogenesis, and promote endometrial angiogenesis, thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

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