1.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
2.Zishen Tiaogan Prescription Treats Diminished Ovarian Reserve in Rats via Keap1/Nrf2/HO-1 Signaling Pathway
Zhongtong LI ; Yaping ZHANG ; Chen YOU ; Qingqing LI ; Yingjie WANG ; Siwen OU ; Taomei XUE ; Chuqi ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):72-80
ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve (DOR) and explore the role of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group (n=12) and a modeling group (n=36). The rats in the modeling group received subcutaneous injection of galactose (350 mg·kg-1) combined with immobilization stress daily. After 28 days of modeling, 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model, estradiol valerate (0.09 mg·kg-1), and low-, medium-, and high-dose (6.39, 12.78, 25.56 g·kg-1, respectively) Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels, respectively, of Nrf2, Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 (SOD2) in the ovarian tissue was detected by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group showed reduced follicles in the ovary, loose arrangement of the follicle granule layer, declined levels of anti-Mullerian hormone (AMH) and estradiol (E2) in the serum, elevated levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) (P<0.01), lowered levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) (P<0.01), and increased accumulation of malondialdehyde (MDA) (P<0.01). In addition, the modeling led to up-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 and HO-1 protein was significantly decreased (P<0.01), the mRNA expression of Nrf2 was significantly decreased (P<0.05), the mRNA expression of HO-1 was significantly decreased (P<0.01), in the ovarian tissue. Compared with model group, the estradiol valerate and low-, medium-, and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index (P<0.01) and serum E2 and AMH levels (P<0.01), declined levels of FSH and LH (P<0.01), increased follicles in the ovary, elevated levels of SOD, CAT, and GSH, and reduced accumulation of MDA (P<0.05, P<0.01). Furthermore, these groups showcased down-regulated protein and mRNA levels of Keap1 (P<0.01), the expression of Nrf2 protein was significantly increased (P<0.01), the expression level of HO-1 protein was increased (P<0.05,P<0.01), and increased positive expression of SOD2 (P<0.01). ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones, down-regulate the expression of Keap1, up-regulate the expression of Nrf2, HO-1, and SOD2, enhance the antioxidant capacity, and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.
3.Clinical Questions Construction in Clinical Practice Guidelines: Based on Case-guided Approach
Yicheng GAO ; Zijin YU ; Yaqi WANG ; Rui FANG ; Cheng WANG ; Yuanyuan LI ; Yingjie DENG ; Xue BAI ; Wenyuan XIANG ; Yutong FEI
Medical Journal of Peking Union Medical College Hospital 2024;16(1):198-203
Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.
4.Current status and progresses of clinical treatment of cancer-associated thromboembolism
Yingjie DI ; Yaoqin XUE ; Aixin OU ; Xiao LI ; Jinrui REN
Chinese Journal of Interventional Imaging and Therapy 2024;21(5):298-301
Cancer-associated thromboembolism(CAT)is one of the most common complications and the second direct cause of mortality in patients with malignant tumors,which seriously affect patients'life quality and prognosis.In recent years,with the deepening of mechanism researches of cancer and thrombosis,treatment strategies of CAT were also improved.The current status and progresses of clinical treatment of CAT were reviewed in this article.
5.Mediating effect of psychological resilience of clinical nurses between structural empowerment and work engagement
Zhihui LIU ; Yuhua ZHU ; Xue LI ; Quanying ZHANG ; Yingjie DU
Chinese Journal of Modern Nursing 2024;30(7):926-931
Objective:To explore the mediating effect of psychological resilience between structural empowerment and work engagement of clinical nurses.Methods:This study was a cross-sectional study. Using the convenient sampling method, a total of 1 723 nurses from three Class Ⅲ Grade A hospitals in Henan Province were selected as the research objects from March to May 2023. The survey was conducted using general information questionnaire, Conditions of Work Effectiveness Questionnaire-Ⅱ (CWEQ-Ⅱ), Nurses Psychological Resilience Scale and Utrecht Work Engagement Scale (UWES). Pearson correlation analysis was used to explore the correlation between structural empowerment, psychological resilience and job engagement. AMOS 24.0 software was used to establish the structural equation model and analyze the mediating effect.Results:A total of 1 723 questionnaires were sent out in this study, and 1 590 were effectively collected, with an effective recovery rate of 92.28%. The total scores of structural empowerment, psychological resilience and job engagement of 1 590 clinical nurses were (70.42±15.61), (96.84±13.15) and (62.24±11.02), respectively. Pearson correlation analysis showed that job engagement was positively correlated with structural empowerment and psychological resilience ( r=0.637, 0.670, P<0.01). The results of structural equation model showed that psychological resilience had a partial mediating effect between structural empowerment and job engagement. The mediating effect value was 0.321, accounting for 48.86% of the total effect. Conclusions:In this study, the structural empowerment, psychological resilience and job engagement of clinical nurses are above the medium level, and psychological resilience has a partial mediating effect between structural empowerment and job engagement. Nursing managers should fully empower nurses at the organizational level, take targeted measures to improve their psychological resilience and enhance their level of work engagement.
6.Association of malnutrition based on Global Leadership Initiative on Malnutrition criteria with the disease activity and adverse clinical outcomes in hospitalized ulcerative colitis patients
Renjuan LIU ; Zibin TIAN ; Xue JING ; Yingjie GUO ; Ailing LIU ; Hanqing LI ; Dandan WANG ; Xueli DING
Chinese Journal of Clinical Nutrition 2024;32(2):98-104
Objective:To investigate the association of malnutrition based on Global Leadership Initiative on Malnutrition (GLIM) criteria with the disease activity and clinical outcomes in hospitalized ulcerative colitis (UC) patients.Methods:Clinical data of 115 patients with UC hospitalized in the Affiliated Hospital of Qingdao University from September 2019 to March 2023 were prospectively analyzed. GLIM and European Society for Clinical Nutrition and Metabolism (ESPEN) 2015 criteria were used for the diagnosis of malnutrition, allowing the analysis of consistency between two diagnostic criteria for malnutrition. The relationship between malnutrition based on GLIM criteria and disease activity and clinical outcome was further investigated. The risk factors of adverse clinical outcomes in UC patients were analyzed using binary logistic regression.Results:GLIM and ESPEN 2015 diagnostic criteria showed high correlation and consistency (AUC=0.875, P<0.001; K=0.809, P<0.001). According to GLIM criteria, the prevalence of malnutrition among hospitalized UC patients was 32.17% (37 cases). Compared with non-malnourished UC patients, the modified Mayo score and C-reactive protein level of malnutrition patients were higher ( P<0.005), and the proportion of patients with severe disease activity was higher ( P=0.005). UC patients in the malnourished group had longer hospital stay ( P<0.001), higher hospitalization costs ( P<0.001), and higher rates of drug escalation/conversion therapy, re-admission and surgery at 12 weeks and 54 weeks ( P<0.05). Binary logistic regression analysis showed that a high Mayo score ( OR=3.606, P=0.016), a high modified Mayo score ( OR=1.346, P=0.009) and malnutrition ( OR=1.430, P=0.012) were independent risk factors for adverse clinical outcomes of hospitalized UC patients at 12 weeks. A high modified Mayo score ( OR=6.491, P=0.011) and malnutrition as per GLIM criteria ( OR=6.693, P=0.033) were independent risk factors for adverse clinical outcomes of hospitalized UC patients at 54 weeks. Conclusions:GLIM and ESPEN 2015 diagnostic criteria show high consistency in the diagnosis of malnutrition in hospitalized UC inpatients. Malnutrition may imply adverse clinical outcomes of hospitalized UC patients, which is an independent risk factor for the adverse clinical outcome of hospitalized UC patients.
7.Clinical and pathological features of intraductal tubulopapillary neoplasms
Jiamei LI ; Jiawen XU ; Zhiyi WANG ; Chang LU ; Yingjie XUE ; Jizhen FENG
Chinese Journal of Hepatobiliary Surgery 2023;29(3):190-194
Objective:To investigate the clinical and pathological features and improve the acknowledgement of intraductal tubulopapillary neoplasm (ITPN) of pancreas.Methods:Six cases with ITPN in the Shandong Provincial Hospital Affiliated to Shandong First Medical University combined with 40 cases from PubMed and CNKI were retrospectively analyzed. There were 25 males and 21 females, aged (58.6±16.0) years. The clinical manifestations, pathological features, treatment and so on were analyzed.Results:All cases were treated with surgery. The main clinical symptoms were upper abdominal pain and discomfort (23 cases, 50.0%), followed by jaundice (9 cases, 19.6%). Seven cases (15.2%) had no clinical symptoms. Three cases (6.5%) had low back discomfort, chills and other rare symptoms, and 4 cases (8.7%) had no clinical symptoms mentioned in the literature. Tumors of 27 cases (58.7%) located in the head of the pancreas, 9 cases (19.6%) in the body and tail, 4 cases (8.7%) in the whole pancreas, 3 cases (6.5%) in the body, 2 cases (4.3%) in ampulla and 1 case (2.2%) in head and body. Most of the tumors located in the main pancreatic duct. Microscopically, back-to-back tubular glands were densely arranged, parts of them with papillary structure, with obvious cell atypia and many mitoses. Twenty-two cases (47.8%) of ITPN were completely confined to the pancreatic duct, and 24 cases (52.2%) were with associated invasive carcinoma. Tumor cells were positive for cytokeratin 7 and mucin 1, but negative for cytokeratin 20, synaptophysin, chromogranin and trypsin. Mucin 2, mucin 5AC and mucin 6 were negative in most cases. Ki-67 ranged from 10% to 70%.Conclusion:Pancreatic ITPNs were mostly located in the pancreatic head, confined to the main pancreatic duct, and were mostly manifested as pain and discomfort in the upper abdomen. Surgery was the main treatment. Tumors cells of ITPN were arranged in tubular and papillary, with severe epithelial atypia and special immunophenotype, parts of cases accompanied with associated invasive carcinoma.
8.A multicenter study of R-ISS staging combined with frailty biomarkers to predict the prognosis and early death in newly diagnosed elderly multiple myeloma patients
Yingjie ZHANG ; Hua XUE ; Mengyao LI ; Jianmei XU ; Xinyue LIANG ; Weiling XU ; Xiaoqi QIN ; Qiang GUO ; Shanshan YU ; Peiyu YANG ; Mengru TIAN ; Tingting YUE ; Mengxue ZHANG ; Yurong YAN ; Zhongli HU ; Nan ZHANG ; Jingxuan WANG ; Fengyan JIN
Chinese Journal of Geriatrics 2023;42(10):1207-1212
Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.
9.Bayesian Network Meta-analysis of Therapeutic Efficacy and Safety of Different Chinese Patent Medicine Injection for Pro- moting Blood Circulation and Removing Blood Stasis Combined with Routine Treatment after PCI
Chushuo SHI ; Jiayue LIU ; Yingjie HUANG ; Weiqi XUE ; Junmao WEN ; Junzhe LI ; Wei WU
China Pharmacy 2019;30(16):2267-2274
OBJECTIVE: To systematically evaluate the difference in therapeutic efficacy, safety and cardiac function of Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment after percutaneous coronary intervention (PCI), and to provide evidence-based reference for clinical drug use. METHODS: Retrieved from Cochrane library, PubMed, Embase, CNKI, Wanfang database and Chinese sci-tech periodicals database, RCTs about different Chinese patent medicine injection for promoting blood circulation and removing blood stasis combined with routine treatment (trial group) versus routine treatment (control group) after PCI were collected. After screening the literature and extracting the data, the quality of the included studies was evaluated by modified Jadad scale. Bayesian network Meta- analysis was performed by using Stata 14.0 software and Markov Chain-Monte Carlo method. RESULTS: A total of 15 RCTs involving 1 364 patients were included, involving Salvia miltiorrhiza injection, Puerarin injection, Yiqi fumai injection, Xuebijing injection, Shenfu injection, Shuxuetong injection, Salvia miltiorrhiza and ligustrazine injection, Rhodiola wallichiana injection, Danhong injection. Results of Meta-analysis showed that in the aspect of improving total response rate of ECG, 8 kinds of intervention measures were involved;compared with control group, 7 kinds of intervention measures could improve the total response rate of ECG of trial group except for Shenfu injection (P>0.05); network Meta-analysis ranking showed that S. miltiorrhiza injection>Puerarin injection>Shenfu injection>S. miltiorrhiza and ligustrazine injection>Shuxuetong injection>R. wallichiana injection> Danhong injection>routine treatment. In terms of reducing adverse cardiovascular events (MACE) incidence,8 kinds of intervention measures were involved; compared with control group, 7 kinds of intervention measures could reduce the MACE incidence of trial group except for Puerarin injection (P>0.05); network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection>Danhong injection>Xuebijing injection>Shuxuetong injection>S. miltiorrhiza injection>R. wallichiana injection> Puerarin injection>routine treatment. In terms of improving left ventricular ejection fraction (LVEF) after treatment, 8 kinds of intervention measures were involved; compared with control group, 7 intervention measures could significantly improve LVEF after treatment of trial group except for R. wallichiana injection (P>0.05); network Meta-analysis ranking showed that S. miltiorrhiza and ligustrazine injection>Yiqi fumai injection>Danhong injection>Shenfu injection>S. miltiorrhiza injection>Shuxuetong injection>R. wallichiana injection>routine treatment. CONCLUSIONS: Compared with routine treatment, S. miltiorrhiza injection is the best in improving total response rate of ECG; S. miltiorrhiza and ligustrazine injection is the best in reducing MACE incidence and improving LVEF after treatment.
10.Temporary titanium plate screwing in open reduction and internal fixation for displaced acetabular fracture
Jin KANG ; Yongle LI ; Tiegang ZHENG ; Xiaowei LIU ; Yingjie XU ; Lin MA ; Yang XUE ; Tiejun LI ; Xiandong FAN ; Chao LI ; Jingxing LIU ; Jie GAO ; Wenhai QIAO
Chinese Journal of Orthopaedic Trauma 2019;21(3):231-235
Objective To explore the efficacy of temporary titanium plate screwing for positional maintenance in reduction and internal fixation for displaced acetabular fractures.Methods A retrospective study was conducted of the 28 patients (28 hips) with displaced acetabular fracture who had been treated by open reduction and internal fixation from October 2013 to March 2016.They were 20 males and 8 females,aged from 24 to 68 years (average,42.3 years).The time from injury to surgery ranged from 7 to 21 days(average,14.5 days).According to the Letournel-Judet classification,there were 2 posterior column fractures,4 transverse fractures,5 posterior column plus posterior wall fractures,6 transverse plus posterior wall fractures,2 T-shaped fractures,3 anterior and posterior transverse fractures and 6 double column fractures.The posterior acetabular approach or combined anterior and posterior approach was used.In all the patients temporary titanium plate screwing was conducted to fix one side of the fracture so as to facilitate accomplishment of open reduction and internal fixation without losing the indirect anatomic reduction of the intraarticular fracture.After the open reduction and internal fixation was accomplished,the temporary screw fixation was removed in 26 patients but retained in 2 patients as needed.The reduction quality,complications and outcomes at the final follow-ups were recorded.Results All the 28 patients were followed up for 10 to 36 months (mean,15.6 months).By the Matta criteria,anatomical reduction was achieved in 26 cases,unsatisfactory reduction in one and poor reduction in one,yielding an anatomic reduction rate of 92.9%.By the improved Mere d'Aubigne & Postel criteria,the clinical outcomes at the final follow-up were excellent in 27 cases and good in one,yielding a good to excellent rate of 100%.Postoperatively,heterotopic ossification of different severities occurred in 11 cases but did not affect their joint function;transient paralysis of the sciatic nerve was reported in 6 cases but recovered 3 months after surgery.No complications like avascular necrosis of the femoral head or walking pain were observed during follow-ups.Conclusion Temporary fixation with titanium plate screws during open reduction and internal fixation for displaced acetabular fractures can effectively improve the reduction and fixation of the articular surface,leading to satisfactory short-term clinical outcomes.

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