ObjectiveTo investigate the mechanism of the modified of Bazhentang combined with Guishentang in improving pregnancy outcomes in mouse models of embryo implantation dysfunction by regulating T helper 1/T helper 2 （Th1/Th2） immune balance. MethodsEighty ICR female mice were randomly divided into four groups （n=20 per group） on gestational day 1 （GD1）： control， model， western medicine， and traditional Chinese medicine （TCM） groups. Except for the control group， all mice received mifepristone solution （0.2 mg/mouse） via oral gavage on GD4 to induce embryo implantation dysfunction. The TCM group received a water decoction of the modified of Bazhentang combined with Guishentang （20.8 g·kg^-1）， with the western medicine group administered dydrogesterone （3.9 mg·kg^-1）， and the control/model groups given equal volumes of saline. All treatments were administered once daily from GD1 until one day before sample collection. Outcomes included implantation site counts （macroscopic observation）， pregnancy rates， body weight， endometrial histopathology （hematoxylin-eosin staining）， uterine expression of T-box expressed in T cells （T-bet）， GATA-binding protein 3 （GATA3）， interferon gamma （IFN-γ）， and interleukin-4 （IL-4） at protein （Western blot） and mRNA （real-time polymerase chain reaction， Real-time PCR） levels， serum IFN-γ and IL-4 levels （enzyme-linked immunosorbent assay， ELISA）， and Th1/Th2 immune balance evaluated by calculating T-bet/GATA3 and IFN-γ/IL-4 ratios. ResultsCompared to the control group， the model group showed no significant change in pregnancy rate but exhibited a marked reduction in average implantation sites and body weight （P<0.01）. Histopathological analysis revealed endometrial abnormalities， including decreased glandular density， stromal compaction， and absence of nucleolar vacuoles. At the molecular level， uterine tissue in the model group demonstrated significantly upregulated expression of T-bet and IFN-γ （P<0.05， P<0.01）， alongside markedly downregulated GATA3 and IL-4 expression （P<0.05， P<0.01）. Serum analysis confirmed markedly elevated IFN-γ （P<0.01） and reduced IL-4 levels （P<0.01）， resulting in significantly increased T-bet/GATA3 and IFN-γ/IL-4 ratios （P<0.01）. Compared to the model group， pregnancy rates in all treatment groups showed no significant change. Implantation sites and body weight increased substantially （P<0.01）， with restored endometrial morphology characterized by enhanced glandular density， stromal edema， and reappearance of nucleolar vacuoles. Significant downregulation of T-bet and IFN-γ （P<0.01） and upregulation of GATA3 and IL-4 （P<0.05， P<0.01） in uterine tissue were observed. Serum IFN-γ levels were significantly reduced （P<0.05， P<0.01）， while IL-4 levels were significantly elevated （P<0.05）. The Th1/Th2 ratios were significantly decreased （P<0.01）. ConclusionThe modified of Bazhentang combined with Guishentang significantly enhances the number of embryo implantation sites in mice with embryo implantation dysfunction， potentially through modulating T-bet/GATA3 expression， restoring Th1/Th2 immune balance， and improving endometrial receptivity.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

OBJECTIVES: To construct vocal recognition classification models using 6 machine learning algorithms and vocal emotional characteristics of individuals with subthreshold depression to facilitate early identification of subthreshold depression. METHODS: We collected voice data from both normal individuals and participants with subthreshold depression by asking them to read specifically chosen words and texts. From each voice sample, 384-dimensional vocal emotional feature variables were extracted, including energy feature, Meir frequency cepstrum coefficient, zero cross rate feature, sound probability feature, fundamental frequency feature, difference feature. The Recursive Feature Elimination (RFE) method was employed to select voice feature variables. Classification models were then built using the machine learning algorithms Adaptive Boosting (AdaBoost), Random Forest (RF), Linear Discriminant Analysis (LDA), Logistic Regression (LR), Lasso Regression (LRLasso), and Support Vector Machine (SVM), and the performance of these models was evaluated. To assess generalization capability of the models, we used real-world speech data to evaluate the best speech recognition classification model. RESULTS: The AdaBoost, RF, and LDA models achieved high prediction accuracies of 100%, 100%, and 93.3% on word-reading speech test set, respectively. In the text-reading speech test set, the accuracies of the AdaBoost, RF, and LDA models were 90%, 80%, and 90%, respectively, while the accuracies of the other 3 models were all below 80%. On real-world word-reading and text-reading speech data, the classification models using AdaBoost and Random Forest still achieved high predictive accuracies (91.7% and 80.6% for AdaBoost and 86.1% and 77.8% for Random, respectively). CONCLUSIONS Analyzing vocal emotional characteristics allows effective identification of individuals with subthreshold depression. The AdaBoost and RF models show excellent performance for classifying subthreshold depression individuals, and may thus potentially offer valuable assistance in the clinical and research settings.
Humans ; Machine Learning ; Emotions ; Depression/diagnosis* ; Algorithms ; Voice ; Support Vector Machine ; Male ; Female

Objective:To investigate the application value of virtual reality laparoscopic simulator training in laparoscopic transabdominal preperitoneal hernioplasty (TAPP).Methods:The prospective cohort study was conducted. Twenty young physicians from The First Affiliated Hospital of Harbin Medical University with ≥3 years of clinical experience in general surgery and no foundation in laparoscopy were selected for training during July to August 2023. Physicians were divided into two groups based on random number table method. Physicians undergoing virtual reality laparoscopic simulator training were divided into the virtual reality group, and physicians undergoing regular laparoscopic simulator training were divided into the regular group. Two groups of physicians were trained using laparoscopic simulator for 10 days (2 hours for each skill, with a total of 6 hours per day for 3 skills), and the training covered basic laparoscopic surgical skills such as clamping, cutting and suturing and knotting. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups were conducted using the independent sample t test and the paired ttest was used for intra group comparison. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups were conducted using the chi-square test. Results:(1) Physicians situation before training. A total of 20 physicians were selected for eligibility. There were 13 males and 7 females, aged 31(range, 30?34)years. There are 7 males and 3 females in the virtual reality group, with age of (31.5±1.4)years and the TAPP simulation surgery time of (42±4)minutes before training. There are 6 male and 4 female students in the regular group, with age of (31.2±1.0)years and the TAPP simulation surgery time of (42±4)minutes before training. There was no significant difference in gender, age, TAPP simulation surgery time between the two groups of physicians ( P>0.05), confounding bias ensured comparability. (2) Basic skills of physicians before and after training. For physicians in the virtual reality group, the clamping score was 5.1±1.0, the cutting score was 4.9±1.0, the suturing and knotting score was 4.7±1.5 before training. The clamping score was 8.0±1.3, the cutting score was 7.9±1.5, the suturing and knotting score was 6.6±1.3 after training. There were significant differences in the above indicators before and after training ( t=?5.75, ?5.21, ?3.07, P<0.05). For physicians in the regular group, the clamping score was 5.3±1.0, the cutting score was 5.0±1.2, the suturing and knotting score was 4.3±1.5 before training. The clamping score was 7.1±1.2, the cutting score was 6.7±1.3, the suturing and knotting score was 5.7±1.1 after training. There were significant differences in the above indicators before and after training ( t=?3.73, ?3.16, ?2.42, P<0.05). (3) Completion of simulated surgical situations before and after training. The time of completing TAPP simulation surgery for virtual reality group after training was (29±3)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=7.69, P<0.05). The time of completing TAPP simulation surgery for regular group after training was (36±4)minutes, versus (42±4)minutes before training, showing a significant difference before and after training ( t=3.75, P<0.05). The time of completing TAPP simulation surgery of virtual reality group after training was shorter than that of regular group, showing a significant difference between the two groups ( t=?3.89, P<0.05). Conclusion:Both of virtual reality and regular laparoscopic simulator can enhance the basic laparoscopic surgical skills and the proficiency of TAPP simulation surgery of physicians, and the training effect of virtual reality laparoscopic simulators is better.

Objective:To study the factors influencing survival after radical resection in patients with intrahepatic cholangiocarcinoma (ICC), and to construct a nomogram on survival prediction.Methods:The clinical data of 139 patients with ICC who underwent radical resection at the People's Hospital of Zhengzhou University from June 2018 to December 2021 were retrospectively analyzed. There are 69 males and 70 females, aged (59.5±10.2) years old. These patients were divided into two groups based on a 3: 1 ratio by using the random number method: the test group ( n=104) and the validation group ( n=35). Data from the test group was used to construct a nomagram and data from the validation group was used to validate the predictive power of the nomagram. Univariate and multivariate Cox regression analyses were used to analyse factors influencing survival on the test group patients and to construct a nomogram. The predictive accuracy of the nomogram was determined by receiver operating characteristic (ROC) curves, concordance index (C-index) and calibration curves. Results:The results of the multivariate regression analysis showed that a combined hemoglobin, albumin, lymphocyte and platelet immunoinflammation (HALP) score <37.1 ( HR=1.784, 95% CI: 1.047-3.040), CA19-9 > 35U/ml ( HR=2.352, 95% CI: 1.139-4.857), poorly differentiated tumor ( HR=2.475, 95% CI: 1.237-4.953) and vascular invasion ( HR=1.897, 95% CI: 1.110-3.244) were independent risk factors that affected prognosis of patients with ICC after radical resection (all P<0.05). The AUCs of the nomogram in the test group in predicting the overall survival at 1, 2 and 3 years of patients with ICC after radical resection were 0.808, 0.853 and 0.859, respectively. There was good consistency between the prediction of the nomogram and actual observation. The predicted C-index of the total survival period of the test group was 0.765 (95% CI: 0.704-0.826), and the C-index of the validation group was 0.759 (95% CI: 0.673-0.845). Conclusion:A HALP score <37.1, CA19-9>35 U/ml, poorly differentiated tumour and vascular invasion were independent risk factors for prognosis of ICC patients after radical resection. The nomogram was established based on the above factors and showed good performance in predicting overall survival after radical resection in patients with ICC.

Objective:To investigate the diagnostic efficacy of MRI-based or CT-based measurements and the combined evaluation methods for preoperative bone quality assessment in patients with cervical degenerative diseases.Methods:Patients who underwent spine surgery for cervical degenerative diseases at the Department of Orthopedics, Huashan Hospital, Fudan University from September 2020 to March 2022 with available preoperative X-ray, CT, MRI and dule energy X-Ray absorptiometry (DEXA) data were included in this study. Vertebral bone quality score (VBQ) based on MRI T1-weightedimages and CT Hounsfiled unit (HU) values of the cervical spine were measured, and a combined diagnostic formula based on the binary logistic regression was constructed. The patients were divided into normal bone mass (T≥-1.0) and osteopenia/osteoporosis groups (T<-1.0). The student's t-test and Chi-square test were performed for comparisons between groups. The Pearson correlation coefficient was also used to investigate the correlation between DEXA-T scores, cervical VBQ and CT HU values. In addition, receiver operating characteristic curve (ROC) were plotted to explore the diagnostic efficacy of VBQ, CT HU and their combined diagnosis. Meanwhile, the corresponding sensitivity and specificity were obtained. Results:A total of 71 patients were included in this study (17 in the normal group and 54 in the osteopenia/osteoporosis group). The student's t-test showed that VBQ (2.90±0.70 vs. 3.83±0.83, t=4.23, P<0.001) and CT HU values (370.26±85.38 vs. 295.20±67.96, t=3.73, P=0.002) were significantly different between the two groups. The area under the ROC curve (AUC) for VBQ and CT values of the cervical spine were 0.81 and 0.75, respectively, and the AUC for the combined diagnostic value constructed on the basis of both was 0.85. Applying VBQ scores alone had a diagnostic sensitivity of 80% and a specificity of 70%, and the combined diagnosis with VBQ and CT HU had a sensitivity of 90% and a specificity of 75%. Person correlation analysis showed a significant correlation between DEXA T value, cervical VBQ value and CT HU value. The detailed formula was: DEXA T score=-0.63×cervical VBQ+0.64 ( r=-0.55, P<0.001), CT HU value=-40.20×cervical VBQ+458.40 ( r=-0.45, P<0.001), DEXA T score=0.006×CT HU-3.47 ( r=0.45, P<0.001). Conclusion:This study confirmed the feasibility of using cervical VBQ values, CT HU values and combined diagnostics for preoperative bone density screening in patients with degenerative cervical spine diseases. This method allows surgeons to perform an initial preoperative bone density screening based on the patient's existing imaging data, and thus could aid in confirming the indication and scheme of surgery. The method could be a powerful tool for preoperative bone density assessment screening in patients with cervical degenerative diseases.

Hypertensive disorder of pregnancy (HDP) involves two major public health issues: mother-infant safety and prevention and controlling major chronic disease. HDP poses a serious threat to maternal and neonatal safety, and it is one of the leading causes of maternal and perinatal morbidity and mortality worldwide, as well as an important risk factor for long-term cardiovascular disease (CVD). In order to explore effective strategies to prevent and control the source of CVD and reduce its risk, we have established a cohort of HDPs in Shenzhen for the primordial prevention of CVD. The construction of the HDP cohort has already achieved preliminary progress till now. A total of 2 239 HDP women have been recruited in the HDP cohort. We have established a cohort data management platform and Biobank. The follow-up and assessment of postpartum cardiovascular metabolic risk in this cohort has also been launched. Our efforts will help explore the pathophysiological mechanism of HDP, especially the pathogenesis and precision phenotyping, prediction, and prevention of pre-eclampsia, which, therefore, may reduce the risk of adverse pregnancy outcomes, and provide a bridge to linking HDP and maternal-neonatal cardiovascular, metabolic risk to promote the cardiovascular health of mothers and their infants.

In recent years, driven by the support of national policies and societal needs for employments, talents in biology majors have been growing rapidly. To foster high-calibre biology talents for the society in the context of the "double world-class initiative" in higher education, this study analyzed the opinion of biology undergraduates in Huzhou University on employment and their professional recognition of biology majors. The aim of this study was to propose a high-quality employments-driven talent training mode for undergraduates in biology majors, so as to serve as a reference for the reform in training modes of other relevant majors.
Humans ; Universities ; Students ; Biology/education*

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.