The biological function and mechanism of IDH1 gene in intrahepatic cholangiocarcinoma cell HuCCT1 / 解放军医学杂志

Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1)gene in proliferation and migration of intrahepatic cholangiocarcinoma(iCCA)cell HuCCT1.Methods HuCCT1 cells with IDH1 gene knockout(HuCCT1IDH1-/-)were constructed by CRISPR/Cas9 gene editing technology.To investigate the capacities of proliferation,migration and invasion of HuCCT1WT(HuCCT1 cells with wild-type IDH1 gene)and HuCCT1IDH1-/-cells,assays of CCK-8,clone formation,scratch and transwell were performed.Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT)associated proteins E-cadherin,N-cadherin,Vimentin,MMP-9,Wnt3a and β-catenin in two groups of cells.The transcriptome sequencing data of HuCCT1WT and HuCCT1IDH1-/-cells were analyzed by bioinformatics methods,Western blotting was used to verify the expression of signaling pathway-related proteins.Results Compared with HuCCT1WT cells,HuCCT1IDH1-/-cells showed the number of proliferation and clone formation significantly reduced(P<0.05),the proportion of cells blocked in G2/M phase was significantly increased(P<0.01),the rate of scratch healing was significantly decreased(P<0.01),and the number of migrated cells(P<0.001)and invaded cells(P<0.05)was significantly reduced.qRT-PCR assay showed that the expression levels of IDH1,Vimentin,MMP-9 and genes related to the regulation of G2/M cycle proliferation,Cyclin A2,Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1IDH1-/-cells(P<0.05),and the expression of CDH1 mRNA encoding E-cadherin was up-regulated(P<0.01);Western blotting assay showed that the expression level of E-cadherin in HuCCT1IDH1-/-cells was significantly increased(P<0.05),and the expression level of N-cadherin,Vimentin and MMP-9 protein was significantly decreased(P<0.05)than that in HuCCT1WT cells.Data of transcriptome sequencing revealed 1476 differentially expressed genes(DEGs)between two groups of HuCCT1 cells.Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response,cell signaling and cell metabolism.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK,Rap1,Hippo and TNF,which are closely related to the regulation of proliferation and invasion of tumor cells.Western blotting verification results showed that compared with HuCCT1WT cells,the relative expression of Wnt3a and β-catenin proteins of HuCCT1IDH1-/-cells was significantly decreased(P<0.05).Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells,including cell proliferation,migration,invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Mechanism of lncRNA MIR4435-2HG targeting miR-376a-3p to regulate the biological behavior of cholangio-carcinoma cells / 局解手术学杂志

Objective To explore the effects of long non-coding RNA(lncRNA)MIR4435-2HG(MIR4435-2HG)on the proliferation,migration,invasion and apoptosis of cholangiocarcinoma cells and its regulatory effect on microRNA-376a-3p(miR-376a-3p).Methods qRT-PCR method was used to detect the expression of MIR4435-2HG and miR-376a-3p in human intrahepatic bile duct epithelial cells HIBEpic and human cholangiocarcinoma cells RBE.si-NC,si-MIR4435-2HG,miR-NC,miR-376a-3p mimics,si-MIR4435-2HG and anti-miR-NC,and si-MIR4435-2HG and anti-miR-376a-3p were transfected into RBE cells,respectively,as the si-NC group,the si-MIR4435-2HG group,the miR-NC group,the miR-376a-3p group,the si-MIR4435-2HG+anti-miR-NC group,the si-MIR4435-2HG+ anti-miR-376a-3p group.MTT method,Transwell chamber method and flow cytometry were used to detect cell proliferation,migration,invasion and apoptosis;dual luciferase reporter gene assay was used to verify the targeting relationship between MIR4435-2HG and miR-376a-3p.Western blot was used to detect the expression of related proteins.Results The expression of MIR4435-2HG was increased in RBE cells,while the expression of miR-376a-3p was decreased(P<0.05).Compared with the si-NC group,the MIR4435-2HG expression,cell viability,and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG group were reduced(P<0.05),the numbers of migrating and invading cells were reduced(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).Compared with the miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the miR-376a-3p group were decreased(P<0.05),the numbers of migrating and invading cells were decreased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).MIR4435-2HG was of targeted regulation on miR-376a-3p.Compared with the si-MIR4435-2HG+ anti-miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG+anti-miR-376a-3p group were increased(P<0.05),the numbers of migrating and invading cells were increased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were decreased(P<0.05).Conclusion Knockdown of MIR4435-2HG can inhibit the proliferation,migration,invasion and induce apoptosis of RBE cells by targeting miR-376a-3p.

Construction and application value of a predictive model for prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective:To investigate the construction and application value of a predictive model for prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 534 patients who underwent Da Vinci robotic radical gastrectomy for gastric cancer in the Fujian Medical University Union Hospital from August 2016 to August 2021 were collected. There were 389 males and 145 females, aged (60±11)years. All 534 patients were randomly divided into the training dataset of 374 cases and the validation dataset of 160 cases with a ratio of 7∶3 based on random number method in the SPSS 25.0 software. Observation indicators: (1) incidence of prolonged surgical duration; (2) intraoperative and postoperative conditions in patients with prolonged surgical duration and without prolonged surgical duration; (3) complications in patients with prolonged surgical duration and without prolonged surgical duration; (4) analysis of risk factors influencing prolonged surgical duration; (5) construction and evaluation of an artificial neural network predictive model for pro-longed surgical duration. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or per-centages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparametric test. Univariate and multivariate analyses were conducted using the Logistic regression model. Based on the results of univariate analysis, a multilayer perceptron was employed to train an artificial neural network pre-dictive model for prolonged surgical duration. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to assess the model′s performance. Results:(1) Incidence of prolonged surgical duration. Of 534 patients, 284 cases underwent total gastrectomy, and 250 cases underwent distal gastrectomy, with operation time of (206±42)minutes and (187±36)minutes, res-pectively. Cases with prolonged surgical duration and without prolonged surgical duration who under-went total gastrectomy were 41 and 243, and cases with prolonged surgical duration and without prolonged surgical duration who underwent distal gastrectomy were 40 and 210. The gender (male, female), age, body mass index (BMI), tumor diameter, tumor location (upper stomach, middle stomach, lower stomach, mixed type), cases with neoadjuvant therapy, cases with preoperative American Society of Anesthesiologists (ASA) score as 1, 2, 3, cases with clinical T staging as stage T1, stage T2, stage T3, stage T4a, cases with clinical N staging as stage N0, stage N1, stage N2, stage N3, cases with clinical TNM staging as stage Ⅰ, stage Ⅱ, stage Ⅲ, cases with surgical resection scope as total gastrec-tomy or distal gastrectomy, cases with digestive tract reconstruction method as Billroth-Ⅰ anasto-mosis, Billroth-Ⅱ anastomosis, Roux-en-Y anastomosis, cases with surgeon experiences as ≤20 cases or >20 cases were 61,20, (61±9)years, (24±3)kg/m2, 4.0(2.5, 5.0)cm, 34, 10, 33, 4, 1, 3, 73, 5, 3, 6, 26, 46, 14, 41, 19, 7, 5, 13, 63, 41, 40, 1, 33, 47, 5, 76 in the 81 patients with prolonged surgical duration, versus 328, 125, (60±11)years, (23±3)kg/m2, 3.5(2.0, 5.0)cm, 129, 71, 227, 26, 6, 45, 382, 26, 73, 100, 118, 162, 211, 180, 52, 10, 138, 108,207, 243, 210, 13,200, 240, 15, 438 in the 453 patients without prolonged surgical duration, showing significant differences in the BMI, clinical T staging, clinical N staging, clinical TNM staging ( t=-3.68, Z=-4.63, -5.53, -5.56, P<0.05), and no significant difference in the gender, age, tumor diameter, tumor location, preoperative ASA score, surgical resec-tion scope, digestive tract reconstruction method, and surgeon experiences ( χ2=0.29, t=-0.95, Z=-1.27, χ2=5.92, Z=-1.46, χ2=0.25, 1.35, 0.87, P>0.05). There was no significant difference in cases with neoadjuvant therapy between them ( P>0.05). (2) Intraoperative and postoperative conditions in patients with prolonged surgical duration and without prolonged surgical duration. The operation time, volume of intraoperative blood loss, the number of lymph nodes dissected, time to postopera-tive first ambulation, time to postoperative anal exhaust, time to postoperative first intake of liquid diet, time to postoperative first intake of semi-liquid diet, duration of postoperative hospital stay were (261±34)minutes, 50(30, 50)mL, 39±15, (2.3±0.6)days, (3.4±0.9)days, (4.1±1.2)days, (5.7±1.2)days, 8.0(7.0, 9.0)days in the 81 patients with prolonged surgical duration, versus (186±29)minutes, 30(20,50)mL, 42±14, (2.2±0.6)days, (3.4±0.8)days, (4.1±1.1)days, (5.7±1.4)days, 8.0(7.0, 9.0)days in the 453 patients without prolonged surgical duration, showing significant differences in operation time, volume of intraoperative blood loss ( t=-20.46, Z=-3.32, P<0.05), and no significant difference in the number of lymph nodes dissected, time to postoperative first ambulation, time to postopera-tive anal exhaust, time to postoperative first intake of liquid diet, time to first intake of semi-liquid diet, duration of postoperative hospital stay ( t=1.87, -0.87, -0.16, 0.28, 0.03, Z=-1.45, P>0.05). (3) Complications in patients with prolonged surgical duration and without prolonged surgical duration. The overall incidence of complications, incidence of surgical complications (abdominal infection, anastomotic fistula, abdominal bleeding, incision-related complications, intestinal obstruction, lymphatic fistula), incidence of medical complications (pulmonary infection, liver-related complications) were 22.22%(18/81), 0, 0, 2.47%(2/81), 0, 8.64%(7/81), 1.23%(1/81), 12.35%(10/81), 1.23%(1/81) in the 81 patients with prolonged surgical duration, versus 13.47%(61/453), 2.65%(12/453), 0.44%(2/453), 1.77%(8/453), 0.44%(2/453), 3.31%(15/453), 0, 7.28%(33/453), 1.55%(7/453) in the 453 patients without prolonged surgical duration, showing a significant difference in the overall incidence of complications ( χ2=4.18, P<0.05), and no significant difference in the incidence of abdo-minal infection, anastomotic fistula, abdominal bleeding, incision-related complications, intestinal obstruction, lymphatic fistula, liver-related complications ( P>0.05). There was no significant difference in the incidence of pulmonary infection between them ( χ2=2.38, P>0.05). (4) Analysis of risk factors influencing prolonged surgical duration. Results of univariate analysis showed that BMI ≥25 kg/m2, tumor located in the lower stomach, clinical T3-T4a stage, clinical N1-N3 stage were correlated factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer ( odds ratio=1.88, 0.40, 6.24, 6.51, 3.08, 3.39, 17.15, 95% confidence interval as 1.03-3.42, 0.21-0.76, 1.40-27.76, 1.50-28.30, 1.43-6.60, 1.29-8.92, 4.84-60.74, P<0.05). Results of multivariate analysis showed that BMI ≥25 kg/m2, clinical T3 stage, clinical N3 stage were independent risk factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer ( odds ratio=2.31, 4.97, 11.08, 95% confidence interval as 1.19-4.46, 1.05-23.55, 2.72-45.13, P<0.05). (5) Construction and evaluation of an artificial neural network predictive model for pro-longed surgical duration. The BMI, tumor location, clinical T staging, and clinical N staging were incorporated into a multilayer perceptron to construct an artificial neural network predictive model for prolonged surgical duration. Results of ROC curve showed that the AUC, accuracy, sensitivity, specificity, positive predictive value, negative predictive value of the predictive model in the training dataset were 0.73 (95% confidence interval as 0.68-0.78), 91.4%, 68.1%, 94.8%, 65.3%, 95.4%. The above indicators of the predictive model in the validation dataset 0.72 (95% confidence interval as 0.65-0.79), 88.1%, 67.6%, 93.7%, 74.2%, 91.5%. Conclusions:BMI ≥25 kg/m2, clinical T3 stage, clinical N3 stage are independent risk factors influencing prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer. The artificial neural network predictive model con-structed based on BMI, tumor location, clinical T staging, and clinical N staging can effectively predict patients at high risk of prolonged surgical duration in Da Vinci robotic radical gastrectomy for gastric cancer.

Study on clinical application evaluation of patient monitor based on real world data / 医疗卫生装备

Objective To establish a comprehensive evaluation system for the patient monitor clinical application based on real world data(RWD)to provide references for levels of medical institutions to purchase patient monitors.Methods RWD method was used to collect clinical application data of the monitors from 14 medical institutions in Guangxi Zhuang Autonomous Region,and a Chinese brand X(including X1 series for mid-end products and X2 series for high-end products)and a foreign brand Y(including Y1 series for mid-end products and Y2 series for high-end products)with the highest market share were selected to construct a monitor clinical application evaluation system involving in five indicators such as clinical efficacy,applicability,reliability,instrument function and service system.Data processing was carried out with Mantel-Haenszel analysis,propensity score analysis and pairwise comparison method to calculate the clinical application evaluation scores of X and Y brands of monitors.Results In the mid-end products,X series gained advantages over Y series in clinical efficacy,reliability and applicability(P＜0.05),while the differences between the service systems were not statistically signifi-cantly(P＞0.05);in the high-end products,there were no significant differences between the clinical efficacy,applicability,reliability and service systems(P＞0.05).Brand X and Y monitors were equipped with similar basic and advanced functions.Conchision The evaluation system established based on real-world data can be able to effectively evaluate the clinical appli-cation of the monitor,which provides references for clinical application evaluation of medical devices in China.[Chinese Medical Equipment Journal,2023,44(11):71-78]

Study on quantitative evaluation of China's internet plus medical service medical insurance payment policy based on three dimensional analysis framework / 中国卫生政策研究

Objective:To provide reference for improving the provincial Internet plus medical service medical insurance payment policy in China.Methods:From three dimensions of policy tools,participants and policy placement,the distribution characteristics of the Internet plus medical service and medical insurance payment related policies that have been issued in 31 provinces of China were analyzed.A total of 58 policy documents were collected,forming 1585 text items.Results:A total of 597 text items were selected for policy tools(X dimension),with supply based,demand based,and environmental based policy items accounting for 20.6%,16.6%,and 62.8%,respectively.A total of 574 text items were selected for the participating entities(Y-dimension),and 414 text items were selected for the policy placement(Z-dimension).Conclusion:There is a structural imbalance in policy tools,and complementarity and coordination should be enhanced.There are significant differences in the application of policy tools among participating entities,and the division of labor and collaboration among participating entities should be deepened.The practicality of policy implementation is not strong,and close connections between links should be strengthened.The distribution of policies among regions is not balanced enough,and policy design should be optimized according to local conditions.

Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia / 中华血液学杂志

Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.

Analgesic Effect of Intrathecal 2R， 6R-HNK on Neuropathic Pain in Female Mice / 中山大学学报(医学科学版)

ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.

Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF / 中山大学学报(医学科学版)

ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 10 mice/group, half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism.@*METHODS@#Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice.@*RESULTS@#Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05).@*CONCLUSION@#BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

The status and influencing factors of presenteeism among clinical nurses: a systematic review / 中华劳动卫生职业病杂志

Objective: To systematically review the status and factors influencing presenteeism among clinical nurses. Methods: In December 2021, CNKI, CBM, Wanfang, VIP, Web of Science, PubMed, Embase, The Cochrane Library, CINAHL, PsyclNFO and other databases were electronically searched to cross sectional studies on the current situation and factors influencing the occurrence of presenteeism among clinical nurses. The search terms mainly included presenteeism, sick at work, Stanford Presenteeism Scale, nurse, level, risk factor, influence, et al. And the search time was from the establishment of the database to November 30, 2021. Literature screening, data extraction and evaluation of the risk of bias in the included literature were done independently by two researchers, and meta-analysis was performed using Stata 15.1 software. Results: A total of 29 studies involving 13 535 clinical nurses were included.The results of the meta-analysis showed that the score of presenteeism was 17.99 [95% CI (17.02-18.95), P =0.000]. Subgroup analysis showed that presenteeism scores were higher in articles published before 2020 (ES=19.28, 95%CI: 18.41-20.15, P=0.000) and in the group of nurses aged 36 to 40 years (ES=19.27, 95%CI: 17.35~21.19, P=0.000), female (ES= 17.04, 95%CI: 14.70-19.39, P=0.000), secondary school education (ES=21.01, 95%CI: 17.76-24.26, P= 0.007), married (ES=17.49, 95%CI: 15.13-19.85, P=0.000), working for 5 to 10 years (ES=17.78, 95%CI: 16.54-19.02, P=0.000), contract (ES=17.05, 95%CI: 15.23-18.87, P=0.000), working in pediatrics (ES= 16.65, 95% CI: 15.31-17.99, P=0.000) and European region (ES =21.21, 95% CI: 20.50-21.93, P=0.000) . Conclusion: Current evidence suggests that clinical nurses are at high risk of presenteeism, which is affected by variety of factors. The managers should pay attention to the physical and mental health of nurses, identify high-risk factors as early as possible and take measures to reduce the occurrence of presenteeism and improve the quality of nursing.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

Associations of TNF-RII rs1061622 With Post-Traumatic Stress Disorder and Their Interplays on Serum Lipids Levels in Adolescents

Objective@#To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents. @*Methods@#PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods. @*Results@#G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD. @*Conclusion@#These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

Timosaponin A III promotes cisplatin sensitivity in A549/DDP cells via JAK-2/STAT3/PD-L1 signaling pathway / 中国药理学通报

Aim To explore the mechanism of timosaponin A III increasing cisplatin sensitization of non-small cell lung cancer cisplatin-resistant A549/DDP cells. Methods The cell proliferation was detected by CCK8,the cell apoptosis was detected by Annexin V/ PI,and the cell cycle distribution was measured by PI. The effect of the combined drug on cell proliferation was detected by cell clone formation. The mRNA expression levels of C-myc, cysteinyl aspartate-specific protease-3 (caspase-3) were detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot and Flow Cytometry were performed for the mechanism study. Results The results of CCK8 and clone formation showed that the timosaponin AM group significantly increased the sensitivity of cisplatin to A549/DDP cells. Compared with the cisplatin group a-lone,the combination of timosaponin AM and cisplatin significantly elevated the apoptosis rate of A549/DDP cells (P < 0.05) , induced cell cycle arrest in G

The Oncolytic Virus Therapy for Non-Small Cell Lung Cancer / 中国生物化学与分子生物学报

Since the oncolytic herpes simplex virus T-VEC was approved in the United States for the treatment of malignant melanoma in 2015, there has been increasing interests in the oncolytic virus therapy. The oncolytic virus therapy also occupies a certain position in the treatment research process of non-small cell lung cancer(NSCLC). Based on the rapid development of genetic engineering and protein engineering, researchers have designed many recombinant oncolytic viruses targeting various specific sites to further improve their targeting and oncolytic effect in order to alleviate symptoms and even cure NSCLC patients. This review introduces the two major classifications of oncolytic viruses, wild type and gene-edited, and how they achieve tumor lysis by specifically targeting and killing tumor cells. We focus on the research progress of oncolytic virus applied alone to treat NSCLC, or combined with chemotherapy, immunotherapies such as chimeric antigen receptor (CAR)-T cell therapy, immune checkpoint inhibitors and other current hot research to treat NSCLC. At the same time, we summarize and discuss the issue of targeted transport, which is of high concern in the academic field of oncolytic virus therapy, and point out that the use of extracellular vesicles as drug carriers has a good potential for development. Finally, we analyze the existing problems and future application prospects in the context of existing basic and clinical studies, to expend new approaches for the treatment of NSCLC, so that it is no longer limited to traditional therapies.

Relationship between home literacy environment and emotional regulation in children: the mediating effect of the parent-child relationship / 中国当代儿科杂志

OBJECTIVES@#To study the impact of the home literacy environment on children's emotional regulation skills and the mediating role of the parent-child relationship between them.@*METHODS@#A stratified cluster sampling approach was employed to select 1 626 preschool children from five kindergartens in Nanjing. Questionnaires were used to collect detailed information on the home literacy environment, children's emotional regulation skills, and the parent-child relationship. A mediation model was established using the Process program in SPSS macro, and the significance of the mediation effect was tested using the Bootstrap method.@*RESULTS@#The findings revealed a positive correlation between the home literacy environment and children's emotional regulation skills (r=0.217, P<0.001), as well as parent-child intimacy (r=0.065, P<0.01). Conversely, a negative correlation was found between the home literacy environment and parent-child conflict (r=-0.129, P<0.001). Additionally, parent-child conflict demonstrated a negative correlation with children's emotional regulation skills (r=-0.443, P<0.001), while parent-child intimacy exhibited a positive correlation (r=0.247, P<0.001). The home literacy environment exerted a significant direct effect on children's emotional regulation skills (β=0.162, P<0.001), and the mediating effect of the parent-child relationship accounted for 25.54% of the total effect.@*CONCLUSIONS@#The home literacy environment significantly influences children's emotional regulation skills, with the parent-child relationship partially mediating this relationship.

Carbonic anhydrase IX-based tumor imaging and therapy: a review / 生物工程学报

Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.

Analysis of in vitro activity and compatibility of Dunhuang Yifang Dabupi Decoction on gastric cancer based on computer-aided drug design / 药学学报

Based on the research system of computer-aided drug design combined with complex network analysis, the potential mechanism of Dunhuang Dabupi Decoction in preventing and treating gastric cancer (GC) is analyzed, and the scientific connotation of its prescription rules is explored through the efficacy grouping. To study the effect of Dabupi Decoction freeze-dried powder solution on the proliferation activity of gastric cancer cells through cell experiments; the TCMSP and TCMID databases were used to collect the compound components of Dabupi Decoction. Swiss Target Prediction is used to predict potential targets of compounds. DrugBank, GeneCards, TTD, and DisGeNET were used to collect potential targets for gastric cancer. Analyze protein interactions of potential targets through the STRING database. DAVID database was used for KEGG enrichment analysis; Dabupi Decoction was divided into Wenzhong group (dried ginger), Yiqi group (ginseng, licorice, Atractylodes macrocephala), nourishing Yin group (Ophiopogon japonicus, Schisandra) and Jiangni group according to its efficacy characteristics. The inverse group (inula) has 4 functional compatibility groups. Cytoscape was used to construct a network of "medicinal flavor-potential active ingredient-key target" respectively, and the network was used to analyze the scientific connotation of the compatibility of efficacy groups. The Schrödinger software was used to verify the molecular docking of the core components and the core targets. The material basis of the Dabupi Decoction to prevent and treat gastric cancer was discovered through the combination of pattern analysis and combined free energy calculation. The core drug was analyzed from the perspective of dynamics through molecular dynamics simulation. Potential targets and representative potential compounds interact with each other. Cell experiments confirmed that Dabupitang freeze-dried powder solution can down-regulate the mitochondrial membrane potential of AGS gastric cancer cells, block the cell cycle in the G0/G1 phase (P < 0.05), and inhibit its proliferation (P < 0.05). The pathways enriched by the four functional groups contained in Dabupi Decoction are mainly distributed in the body's energy metabolism, inflammation-immune system regulation, and cycle-apoptotic functions. Each module is connected by a common target gene and has its own focus. The results of molecular docking showed that the compounds liquiritigenin, quercetin, kaempferol, isorhamnetin, methylophiopogonanone A, etc. may be the effective multi-target components of Dabupi Decoction. Estrogen receptor 1, androgen receptor, ATP-binding cassette superfamily G member 2, epidermal growth factor receptor, glycogen synthase kinase-3 beta and other targets have good affinity with each potential active compound, which may be a potential target of Dabupi Decoction for preventing and treating gastric cancer. Among them, kaempferol and the drug target EGFR not only have good binding ability, but also have good binding stability. This study is based on computer-aided drug design combined with complex network analysis strategies to initially reveal the material basis and molecular mechanism of Dabupi Decoction in the prevention and treatment of gastric cancer. It also explores the scientific connotation of Dabupi Decoction in the prevention and treatment of gastric cancer with different efficacy groups, and its clinical application provide chemical bioinformatics basis.

Efficacy and Mechanism of Yishen Shengjing Prescription in Treatment of Oligoasthenospermia / 中国实验方剂学杂志

ObjectiveWe aimed to investigate the efficacy and mechanism of Yishen Shengjing Prescription （YSP） in the treatment of oligoasthenospermia in rats. MethodThe oligoasthenospermia rat model was established by injection with cyclophosphamide （35 mg·kg-1·d-1） for 5 consecutive days. Rats were randomly assigned into control group （without treating with cyclophosphamide）， model group， low- （YSP-L）， medium- （YSP-M）， and high- （YSP-H） dose （2.91， 5.83， and 11.66 g·kg-1， respectively） groups， Wuzi Yanzongwan （WYW， 1.03 g·kg-1） group， and L-carnitine （0.17 g·kg-1） group， with 8 rats in each group. After 28 days of drug intervention， the body weight， testicular weight， and testicular index of rats were recorded. The sperm quality in epididymis was detected by computer-assisted sperm analysis （CASA） system. Hematoxylin-eosin （HE） staining was employed for observation of testicular tissue morphology. The levels of malondialdehyde （MDA） and superoxide dismutase （SOD） in testicular tissue were detected by colorimetry. The levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） in serum were determined by enzyme-linked immunosorbent assay（ELISA）. TdT-mediated dUTP nick-end labeling （TUNEL） was employed to detect the apoptosis of testicular cells. The protein levels of B cell lymphoma-2（Bcl-2）， Bax， and cleaved Caspase-3 in testicular tissue were detected by Western blot. ResultCompared with the control group， the model group showed decreased body weight， testicular weight and index， sperm concentration and motility （P<0.01） and increased testicular pathological score （P<0.01）. Compared with the model group， the YSP-M， YSP-H， WYW， and L-carnitine groups showed increased body weight， testicular weight， testicular index， sperm concentration and motility and decreased testicular pathological score. After modeling， the SOD level decreased （P<0.01） while the MDA content increased （P<0.01） in the testicular tissue. YSP-H， WYW， and L-carnitine reversed the SOD and MDA level changes caused by modeling. Compared with the control group， the model group exhibited declined T level （P<0.01） and increased FSH and LH levels （P<0.01）. Compared with the model group， YSP， WYW， and L-carnitine increased the T level （P<0.01） and decreased the LH level （P<0.05， P<0.01）. The apoptosis rate of spermatogenic cells in the model group was higher than that in the control group （P<0.01）， whereas YSP-M， WYW， and L-carnitine reversed such changes （P<0.01）. The model group rats showed decreased expression of Bcl-2（P<0.05） and increased expression of Bax and cleaved Caspase-3 （P<0.05， P<0.01）. Compared the model group， YSP-M， YSP-H， WYW， and L-carnitine up-regulated the Bcl-2 expression and down-regulated the cleaved Caspase-3 expression （P<0.05， P<0.01）. ConclusionYSP improved the sperm quality of oligoasthenospermia model rats by regulating the antioxidant system and sex hormone levels and inhibiting the apoptosis of spermatogenic cells.

Chinese Herbal Medicines Prevent and Treat Atopic Dermatitis by Improving Skin Barrier： A Review / 中国实验方剂学杂志

Atopic dermatitis is a chronic， refractory and inflammatory skin disease with the clinical manifestations of severe pruritus and recurrent attacks. It has a high incidence and is closely correlated with other allergic， autoimmune or infectious diseases， which can cause a variety of secondary diseases and mental and psychological disorders， seriously affecting the life quality of patients. Chinese herbal medicines have been used for the prevention and treatment of atopic dermatitis for thousands of years， and many Chinese herbal medicines （including compound prescriptions） effective for this disease have been recorded. These medicines generally have little adverse reactions and the treated patients have low recurrence rate of atopic dermatitis. According to the evidence of modern medicine， the onset of atopic dermatitis is related to the impairment of skin barrier function， abnormal immune response， and abnormal differentiation of mast cells， antigen-presenting cells， and eosinophils. Additionally， it is associated with mental， endocrine， metabolic and other factors. The defect of skin barrier function and the dysfunction of immune system are the main pathogenesis of atopic dermatitis. In recent years， scientists have achieved certain progress in improving skin barrier function with Chinese herbal medicines. This paper systematically summarizes the studies about the application of Chinese herbal medicines in regulating the expression of epidermal proteins， epidermal lipids， aquaporins， tight junction proteins， and antimicrobial peptides in recent 10 years， aiming to clarify the pathological mechanism and provide reference for the clinical research and application of Chinese herbal medicines in the treatment of atopic dermatitis.

Efficacy of basiliximab in the treatment of 87 cases of steroid-refractory or steroid-dependent acute graft-versus-host disease / 中华血液学杂志

Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.