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.

Objective To construct a global model of cardiac surface motion based on average intensity projection(AIP)image.Methods The cine magnetic resonance imaging data were divided into training set and test set for model construction and validation.The datum points were obtained on the AIP surface point cloud,and the corresponding points of each cardiac phase surface point cloud were found based on surface features.Principal component analysis was used to extract feature information,establish the mapping relationship between the datum points and the corresponding points,and construct a model for predicting each temporal phase surface point cloud from the AIP surface point cloud.Results The RMSE of the model on test set for corresponding point prediction ranged from(0.209±0.020)mm to(0.841±0.074)mm,while the Euclidean distance for each time phase surface point cloud prediction ranged from(1.399±0.029)mm to(1.658±0.100)mm.Conclusion The proposed global model exhibit high accuracy and can provide a reference for image segmentation and clinical treatments.

Objective To construct a global model of cardiac surface motion based on average intensity projection(AIP)image.Methods The cine magnetic resonance imaging data were divided into training set and test set for model construction and validation.The datum points were obtained on the AIP surface point cloud,and the corresponding points of each cardiac phase surface point cloud were found based on surface features.Principal component analysis was used to extract feature information,establish the mapping relationship between the datum points and the corresponding points,and construct a model for predicting each temporal phase surface point cloud from the AIP surface point cloud.Results The RMSE of the model on test set for corresponding point prediction ranged from(0.209±0.020)mm to(0.841±0.074)mm,while the Euclidean distance for each time phase surface point cloud prediction ranged from(1.399±0.029)mm to(1.658±0.100)mm.Conclusion The proposed global model exhibit high accuracy and can provide a reference for image segmentation and clinical treatments.

Objective To predict the intervention targets of empagliflozin(EMPA),a specific inhibitor of sodium-glucose cotransporter 2(SGLT2),in gastric adenocarcinoma through comprehensive network pharmacology,and to validate the effects and the molecular mechanisms of EMPA through cellular and molecular biology experiments.Methods Bioinformatics analysis of gastric adenocarcinoma was conducted to assess the correlation between gastric adenocarcinoma prognosis and SGLT2 expression.Network pharmacology was utilized to identify shared targets of EMPA and gastric adenocarcinoma.AGS cells,a human gastric adenocarcinoma cells line,were incubated with EMPA at different concentrations for 24 h and,then,cell proliferation was assessed using the CCK8 assay.After AGS cells were incubated with EMPA at the doses of 0,3,and 6 mmol/L,real-time cell analysis(RTCA)and 5-ethynyl-2-deoxyuridine(EdU)incorporation were used to evaluate EMPA's inhibitory effects on the proliferation of the AGS cells.In addition,wound healing and Transwell assays were performed to assess the inhibitory effect of EMPA on the migration and invasion of the APC cells and Western blot analysis was conducted to examine the expression of mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR).BALB/c(nu/nu)nude mice were implanted with 5x106 AGS cells in the axilla.The mice were divided into three groups,a control group,a low-dose group,and a high-dose group,each consisting of 7 mice.After one week,the control group received daily intraperitoneal injections of normal saline,while the low-dose group and high-dose group received daily intraperitoneal injections of EMPA at the doses of 3 mg/kg and 5 mg/kg,respectively.The tumor volume was measured one week after the drug intervention started.Results Gastric adenocarcinoma patients with low expression of SGLT2 exhibited longer survival time and higher survival rate than those with high expression of SGLT2 did.A total of 104 EMPA-related potential targets and 2028 targets associated with gastric adenocarcinoma were identified.Among these,45 targets associated with gastric adenocarcinoma overlapped with potential targets of EMPA.Further analysis revealed 10 relevant pathways and 4 core genes.The core genes were cyclin-dependent kinase 4(CDK4),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),mTOR,and cyclin El(CCNE1).CCK-8 assay revealed that EMPA at concentrations ranging from 0.39 to 50 mmol/L effectively inhibited the proliferation of AGS cells.RTCA results indicated a downward shift in the cell growth curve.In comparison to the findings for the control group,EdU assay demonstrated that EMPA at the concentrations of 3 mmol/L and 6 mmol/L significantly inhibited AGS cell proliferation(P＜0.05).Results from wound healing and Transwell assays indicated a decrease in the levels of cell migration and invasion(P＜0.05)and,notably,there was a significant difference between the high and low-dose EMPA groups(P＜0.05).Western blot showed no statistically significant difference in the expression of total mTOR protein between the groups.However,the expression of p-mTOR in the 3 mmol/L and 6 mmol/L EMPA groups decreased compared to that of the control group(P＜0.05),with the 6 mmol/L EMPA group exhibiting a more pronounced reduction(P＜0.05).Nude mice xenograft tumor experiment demonstrated that,compared to that of the control group,the tumor volumes in the EMPA-treatment groups were significantly reduced(P＜0.05),with the high-dose group showing a more pronounced reduction(P＜0.05).Conclusion EMPA inhibits the abnormal proliferation and migration of gastric adenocarcinoma cells,potentially through the modulation of mTOR protein activation.This study provides new potential medication and intervention targets for gastric adenocarcinoma treatment.

ObjectiveTo explore the current status and influencing factors of intensive care unit (ICU) nurses' knowledge-attitude-practice (KAP) about patients' early ambulation, so as to provide guidance for formulating appropriate early ambulation intervention strategies. MethodsFrom March to April of 2018, 220 ICU nurses from 4 ClassⅢ Grade A general hospitals were selected as participants in this study by convenience sampling. General Information Questionnaire and Investigation Questionnaire for KAP on Patients' Early Ambulation were used and the multivariate stepwise regression analysis was conducted to analyze the influencing factors. ResultsA total of 211 valid questionnaires were collected. The ICU nurses achieved (7.60±1.35)points from the knowledge on patients' early ambulation and (19.13±2.25) points from the attitude and (15.02±4.13) points from the practice; regression analysis indicated that working length in ICU, and whether there was any early ambulation plan were the influencing factors of the ICU nurses' knowledge on patients' early ambulation; job title, whether had related training experience and whether there was any early ambulation plan were the influencing factors of the ICU nurses' attitude on patients' early ambulation; whether specialized in ICU and whether there was any early ambulation plan were the influencing factors of the ICU nurses' practice on patients' early ambulation(P＜ 0.05). ConclusionsICU nurses' knowledge and attitude on patients' early ambulation are good, however the practice is not satisfying. ICU managers should face up to the current status of patients' early ambulation, work out patients' early ambulation plans for this medical institution, strengthen the training for the ICU medical staff, and promote ICU patients' standard early ambulation.

Objective Through studying the extracorporeal membrane oxygenation (ECMO)alleviating kidney damage caused by unstable circulation function following brain deaths to improve the utilization rate of donation after brain death (DBD) for renal transplantation.Methods Randomly selected 60 DBD patients with unstable circulatory function were randomly divided into 3 groups according to the time of perfusion by ECMO.The first group used ECMO perfusion for 2 h,group 24 h and group 36 h.At the same time,20 cases of stable DBD were randomly selected as the control group.The incidence of primary graft failure,delayed graft function and acute rejection,renal function recovery time,urine volume on the first day after surgery,creatinine and urea nitrogen one year after surgery were compared between two groups.Results The incidence of delayed recovery of renal function in experimental groups 1,2,3 and control group was 10％ (2/20),15％ (3/20),5％(1/20) and 10％ (2/20) respectively.The incidence of acute rejection in experimental groups 1,2,3 and control group was 30％ (6/20),25％ (5/20),35％ (7/20) and 25％ (5/20) respectively.There were no statistically significant differences between the experimental groups and the control group (P ＞0.05).The mean renal function recovery time in the experimental groups 1,2,3 and control group was (9.6 ± 2.0),(9.7 ± 2.7),(9.5 ± 1.9) and (7.3 ± 3.1) days respectively.The average urine volume in experimental groups 1,2,3 and control group was (3 405 ± 755),(3 300 ±600),(3 810±825),and (3 600 ± 80) mL respectively.In experimental groups 1,2,3 and control group,the average creatinine level was (92 ± 28),(92 ± 28),(101 ± 31),and (98 ± 30) μmol/L respectively.The average urea nitrogen in experimental groups 1,2,3 and control group was (4.2 ± 2.2),(5.6 ± 2.6),(5.2 ± 2.6) and (5.5 ± 2.5) mmol/L respectively.The recovery time of renal function in the experimental groups was longer than that in the control group (P＜0.05),but there was no significant difference among the experimental groups (P＞0.05).There was no statistically significant difference between the experimental groups and the control group in urine volume one day after surgery and kidney function one year after transplantation (P＞0.05).Only recovery time after operation of the DBD with the unstable circulation function assisted by EMCO was slightly longer than that with stable circulation function,while the rest indexes showed no statistically significant difference.Conclusion DBD with unstable circulation function with ECMO auxiliary circulatory function can protect the renal function and increase the utilization rate of donor organs.

Objective To explore the effect of depression on loneliness in medical students',and the mediating effects of introverted personality and social support.Methods EPQ,UCLA,SSRS,and POMS questionnaire were used,and surveyed data was collected from Dalian Medical University medical students.Results The scores of depressive mood,introverted personality,social support and loneliness were (17.77±4.45),(11.97±5.21),(34.52±6.15) and (38.02±6.36).Depression was positively related to loneliness and introverted personality (r=0.286,0.508,P＜0.01),and social support was negatively related to loneliness (r =-0.443,P＜0.01).Introverted personality was positively related to loneliness(r=0.401,P＜0.01).The total effect value was 0.670.The mediating effect of introversion as mediator variable was 0.221,accounting for 33％ of the total effect.Social support as intermediary variable,intermediary effect value was 0.449,accounting for 67％ of the total effect.Standard value of mediating effect between depression and introverted personality showed as 0.508 (95％CI=0.475-0.725,P＜0.0i),standard value of mediating effect between depression and social support showed as-0.150 (95％CI=0.989-1.469,P＜0.01),introverted personality was the mediating variant of depression and loneliness,standard value of mediating effect was 0.156 (95％ CI=0.080-0.232,P＜0.01),social support was the mediating variant of depression and loneliness,standard value of mediating effect was 0.317 (95％ CI=0.177-0.457,P＜0.01).Conclusions Introverted personality and social support play an intermediary role between depression and loneliness.

Objective To explore the clinicopathological features and prognostic significance of human epidermal growth factor receptor 2 (HER2) in gastric carcinoma. Methods Pathological data of 127 patients with gastric carcinoma were retrospectively analyzed. HER2 expressions of all patients were detected by immunohistochemistry (IHC). 119 (93.7 %) patients were undergone R0 dissection and 123 (96.9 %) cases received D2 lymph nodes dissection. 51 (40.2 %) patients received adjuvant chemotherapy. The proportional differences of clinicopathological features for patients between HER2-positive and HER2-negative were compared, including the patients' survival. Results HER2 overexpression rate was 8.7 % (11/127) in gastric carcinoma patients. For the patients with HER2-positive and HER-negative, the lymph node metastasis rates were 100.0 % (11/11) and 81.9 % (95/116), respectively (P= 0.041). The 3-year overall survival (OS) rates for HER2-positive and HER2- negative patients with gastric carcinoma were 32.7 % and 42.9 % (P=0.413), and the 5-year progression free survival (PFS) rates were 27.3 % and 42.2 % (P = 0.354), respectively. Among patients with HER2-negative, 3-year OS rate for patients with surgery plus adjuvant chemotherapy was 55.3%, compared with 35.4%for patients with surgery alone (P=0.015), and the 3-year PFS rates were 53.3 % and 35.3 % (P= 0.038), respectively. Among patients with HER2-positive patients, 3-year OS rate for patients with surgery plus adjuvant chemotherapy was 0, compared with 75.0%for patients with surgery alone (P=0.002), and the 3-year PFS rates were 0 and 60.0% (P=0.004). Conclusions HER2 is expressed in gastric carcinoma tissue, related to lymph node metastasis. HER2 status are not correlated with the prognosis for gastric carcinoma patients, however, it is likely to be a predictive marker for adjuvant treatment after surgery for patients with gastric carcinoma.

Next generation sequencing (NGS) has developed very rapidly in the last decade. Compared with Sanger sequencing, NGS has the advantages of high sensitivity and high throughput. Movement disorders are a common type of neurological disease. Although traditional linkage analysis has become a standard method to identify the pathogenic genes in diseases, it is getting difficult to find new pathogenic genes in rare Mendelian disorders, such as movement disorders, due to a lack of appropriate families with high penetrance or enough affected individuals. Thus, NGS is an ideal approach to identify the causal alleles for inherited disorders. NGS is used to identify genes in several diseases and new mutant sites in Mendelian movement disorders. This article reviewed the recent progress in NGS and the use of NGS in Mendelian movement disorders from genome sequencing and transcriptome sequencing. A perspective on how NGS could be employed in rare Mendelian disorders is also provided.
Alleles ; Genetic Linkage ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Movement Disorders ; diagnosis ; genetics ; Sequence Analysis, DNA ; Transcriptome