BACKGROUND:Superovulation is a common therapy in assisted reproductive technology.In clinical practice,some patients experience repeated superovulation to get pregnant. OBJECTIVE:To explore the effect of repeated superovulation on the developmental potential of oocytes in mice and humans. METHODS:Both animal experiments and retrospective clinical research were conducted.The animal study involved 90 SPF grade ICR 8-week-old female mice,who were randomly divided into three groups for 1,3,and 5 superovulations,respectively.The clinical study involved 306 patients who had undergone three consecutive in vitro fertilization cycles.The number of ovules obtained and embryonic development in different cycles were compared. RESULTS AND CONCLUSION:(1)The animal study indicated that repeated superovulation did not affect the embryonic development or developmental speed of mouse embryos.Similarly,there was no significant difference in the mouse blastocyst apoptosis,DNA damage,or the formation of inner cell mass and trophectoderm(P>0.05).(2)The clinical study also revealed no significant differences in the number of retrieved oocytes(8.60±5.04,8.58±4.87,and 8.38±4.63,P=0.81)and transferable embryos(2.42±1.99,2.40±1.92,and 2.64±2.00,P=0.26)over the three cycles.(3)In both the young group(<35 years)and the old group(≥35 years),the embryo quality was not affected by repeated superovulation(P>0.05).(4)These findings show that repeated superovulation does not affect the developmental potential of oocytes in mice and humans.

Objective To study the expression and clinical significance of neural Wiskott-Alrdich syndrome protein(N-WASP)in pla-centas with preeclampsia.Methods This study included a total of 65 pregnant women:15 in the early-onset preeclampsia group,15 in the early-onset control group,15 in the late-onset preeclampsia group,and 20 in the late-onset control group.Real-time fluorescence quan-titative PCR(RT-qPCR)was used to detect the relative expression of N-WASP mRNA in placental tissues.Western blotting and immu-nohistochemistry were used to detect the expression and position of N-WASP protein in placental tissues from each group.Results RT-qPCR revealed significantly lower N-WASP mRNA expression levels in the placental tissue of the early-onset preeclampsia group compared to those in the early-onset control group(0.50±0.19 vs.0.93±0.73,P＜0.05).The N-WASP mRNA expression levels in late-onset preeclampsia placenta were significantly lower than those in the late-onset control group(0.83±0.34 vs.1.15±0.34,P＜0.05).Western blotting revealed significantly lower N-WASP protein expression in the placental tissue of early-onset preeclampsia compared to that in the early-onset control group(0.35±0.17 vs.0.72±0.21,P＜0.05).The N-WASP protein expression in late-onset preeclampsia placenta was significantly lower than that in the late-onset control group(0.39±0.16 vs.0.76±0.20,P＜0.05).The N-WASP mRNA expression in the placenta negatively correlated with the occurrence of early-onset(r =-0.37,P = 0.042)and late-onset preeclampsia(r =-0.39,P = 0.019).Immunohistochemistry revealed that N-WASP protein was localized in the cytoplasm of syncytiotrophoblasts,cytotrophoblasts,villous stromal cells,and vascular endothelial cells.Conclusion The low expression of N-WASP may be closely associated with preeclampsia.

OBJECTIVE To evaluate the innovation and sustainable development ability of traditional Chinese medicine(TCM) preparation in medical institutions, and to provide reference for the decision-making of administrative departments and the sustainable development of TCM preparation in hospitals. METHODS Based on the information data of 133 medical institutions in Zhejiang Province, analytic hierarchy process was used to construct the evaluation system of innovation and sustainable development ability of TCM preparation of medical institutions, and the prediction model of evaluation system of TCM preparation room/center was built by back propagation neural network. RESULTS The evaluation index system for innovation and sustainable development of TCM preparations in medical institutions included 4 second-level indexes and 19 third-level indexes. Among them, the number of varieties developed, the number of over one million varieties, the number of registered varieties, the way of research and development, and the area of preparation room had higher weight values, which were 0.15758, 0.12928,0.09343, 0.07879 and 0.07458, respectively. The entropy weight method and analytic hierarchy process index weights were used to construct the back propagation neural network. The overall correlation coefficients of the training models of the Levenberg-Marquardt algorithm and the Scaled Conjugate Gradient algorithm were 0.98983 and 0.93480, respectively. CONCLUSION This study establishes a scientific and effective comprehensive evaluation system for the innovation and sustainable development ability of TCM preparations in medical institutions, which can realize the prediction and evaluation of the comprehensive ability of TCM preparations in medical institutions.

In prokaryotes like Escherichia coli (E. coli), transcription tends to be coupled with translation, which is usually manifested in the mutual regulation of transcription and translation such as transcription polarity, transcription attenuation and synchronization of transcription and translation rates. Indirect coupling and physical coupling are two different models of the coupling. Indirect coupling maintained by the alarmone (p)ppGpp may require the assistance of DksA and TufA proteins. Physical coupling could be divided into those mediated by NusG or RfaH factors and those induced via “collision” under non-factor condition. Changes in transcription or translation in response to pressure will lead to mutual transitions among several coupling modes. Coupling is necessary for normal gene expression, and its release will contribute to adverse events such as transcription termination, R-loop formation, conflict between replication and transcription and mRNA cleavage. The related technologies of structural biology have clearly demonstrated the structural details and characteristics of partial coupled expressomes. These technologies, combined with methods like multiomics analysis, will provide deeper insights into the coupling. Significantly, the study of the coupling may bring new ideas for development of the targeted antibiotics.

Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

To investigate the associations of serum gamma-glutamyl transferase (GGT) levels with the risk of cardiovascular disease (CVD) and its subtypes in patients with type 2 diabetes mellitus (T2DM) in Jiangsu Province.Methods:The participants were enrolled in the Comprehensive Research project regarding 'Prevention and Control of Diabetes' in Jiangsu Province. The baseline survey was conducted from 2013 to 2014, and follow-up until December 31, 2021. After excluding the participants who self-reported with chronic liver disease/stroke/coronary heart disease at baseline survey and those with incomplete information on GGT, a total of 16 147 T2DM patients were included in the final analysis. Cox proportional hazard regression models were used to calculate the hazard ratio ( HR) and their 95% CI of GGT for CVD, myocardial infarction, and stroke. Restricted cubic spline models were applied to analyze the dose-response relationship between GGT and the risk of CVD and its subtypes. Results:During the median follow-up time of 8.02 years, 2 860 CVD cases were registered, including 196 cases of myocardial infarction and 2 730 cases of stroke. Multivariate Cox proportional risk regression model indicated that compared to the lowest serum GGT level group, the highest GGT level group had a 24% increased risk of CVD ( HR=1.24, 95% CI: 1.09-1.41) and a 23% increased risk of stroke ( HR=1.23, 95% CI: 1.08-1.40). The restricted cubic spline model showed a nonlinear dose-response relationship between GGT and the risk of CVD, myocardial infarction, and stroke in T2DM patients. Conclusions:High levels of GGT may be associated with an increased risk of cardiovascular disease in T2DM patients, which needs further exploration and validation in future clinical practice.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To construct an analytic method aimed at the characteristics of the commonly method of supplementing and pouring of acupuncture based on the analysis and modeling of ultrasound images around acupoint region in the process of acupuncture.Methods:A total of 7 healthy subjects who underwent physical examination in Beijing Zhongguancun Hospital from June,2022 to June,2023 were selected,and their Kongzui acupoints were acupunctured by 10 acupuncturists with associate senior title as 4 kinds of acupuncture manipulations included reinforcing by twisting and rotating(RFTR),reducing by twisting and rotating(RDTR),reinforcing by lifting and thrusting(RFLT),and reducing by lifting and thrusting(RDLT).The B-ultrasound diagnostic device was used to collect the images of muscle and fascial tissue below the acupoint,so as to construct the model of images.The definition of virtual acupuncture point was adopted to study the regulation of perturbation of subcutaneous tissue that was caused after the skin was acupunctured by needle.The change regulation of the virtual acupuncture point of muscle bundle below skin at Zuikong acupoint of subjects was analyzed.Results:The difference value of average absolution value between peak and trough of the trajectory of virtual acupuncture point of twisting and rotating was 0.066±0.045,and the average value of amplitude of this method was less than that(0.428±0.276)of lifting and thrusting method,and the twisting and rotating method was uniform and symmetrical,and there was difference between two kinds of acupuncture methods.The characteristics of computer graphics was used to qualify the work effect of lifting and thrusting,and reinforcing and reducing,which showed the heavy insertion and light lifting of RFLT,and showed heavy lifting and light insertion of RDLT,thus distinguished the two methods[(RFLT)and(RDLT)].Conclusions:The ultrasound imaging and computer graphics can be used to analyze the regularity of the common"reinforcing and reducing"method of acupuncture and moxibustion.

Ferroptosis is a novel form of cell death discovered in recent years, characterized by iron-dependent cell death featuring the peroxidation of polyunsaturated fatty acid phospholipids. Recent studies have found that radiotherapy can induce ferroptosis in tumor cells through ionizing radiation, and the combination of radiotherapy with small molecule or nano-scale ferroptosis inducers can inhibit tumor growth and enhance radiosensitization. This review summarizes the mechanisms of ferroptosis and the pathways through which radiotherapy induces ferroptosis, and also explores the potential application prospects of small molecule drugs and nanomaterials in mediating ferroptosis for the radiosensitization of tumor treatment.

Objective:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.