Objective To identify differentially expressed genes(DEGs)during the early stage of differentiation of human embryonic stem cells(hESCs)into insulin-producing cells(IPCs)and construct the microRNA(miRNA)-mRNA regulatory network.Methods The datasets GSE42094 from Gene Expression Omnibus(GEO)were employed in this study and included hESCs,Diff1,Diff2,Diff3,Diff4 and IPCs groups.DEGs in the Diff1 group were selected and gene ontology(GO)and Keyoto Encyclopedia of Genes and Genomes(KEGG)pathway were deciphered.The miRNAs associated with DEGs were predicted and the miRNA-mRNA regulatory network was visualized.Then the predicted miRNA was validated by paper result.Results GO result demonstrated that the significant term of biological process were"cell migration involved in gastrulation"and"SMAD protein signal transduction".The KEGG pathway analysis indicated that"transformating growth factor(TGF)-beta signaling pathway"and"Signaling pathways regulating pluripotency of stem cells"played essential roles for 28 DEGs in the Diff1 group.To predict miRNA associated with DEGs,we found that miR-335-5p may regulate expressions of CDA,IFITM1,FREM1,FGF17 and ROR2 genes.There were 26 miRNAs which were validated by result of paper.Conclusion The miRNA-mRNA regulatory network plays an essential role during the early stage of the induction of IPCs.

Objective To explore the clinical effect of totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunos-tomy for gastric cancer.Methods Ninety cases of gastric cancer patients were seleted,of which 45 cases undergoing Roux-en-Y esophagoje-junostomy for digestive tract reconstruction were set as the control group,while 45 cases undergoing hand-sewn esophagojejunostomy for digestive tract reconstruction were set as the observation group.Patients in the control group underwent laparoscopic-assisted total gastrectomy combined with Roux-en-Y esophagojejunostomy to reconstruct digestive tract,while patients in the observation group underwent totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunostomy to reconstruct digestive tract.The perioperative indicators and complications of patients in the two groups were compared.Results The surgical time,time of esophagojejunostomy,and time to get out of bed after surgery of patients in the observation group were significantly shorter than those in the control group(P<0.05),the pain score 24 hours after surgery was significantly lower than that in the control group(P<0.05).There was no statistically significant difference between the two groups in terms of the incidence of complications or Clavien-Dindo grading(P>0.05).Conclusion Hand-sewn esophagojejunostomy for digestive tract reconstruction has a good clinical effect in gastric cancer during totally laparoscopic total gastrectomy.It can shorten the surgical time and time of esophagojejunostomy,reduce postoperative pain,and accelerate postoperative recovery,whose safety is comparable to Roux-en-Y esophagojejunostomy.

Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P＜0.05 orP＜0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P＜0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P＜0.05 or P＜0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P＜0.05 orP＜0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.

Objective To explore the clinical effect of totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunos-tomy for gastric cancer.Methods Ninety cases of gastric cancer patients were seleted,of which 45 cases undergoing Roux-en-Y esophagoje-junostomy for digestive tract reconstruction were set as the control group,while 45 cases undergoing hand-sewn esophagojejunostomy for digestive tract reconstruction were set as the observation group.Patients in the control group underwent laparoscopic-assisted total gastrectomy combined with Roux-en-Y esophagojejunostomy to reconstruct digestive tract,while patients in the observation group underwent totally laparoscopic total gastrectomy combined with hand-sewn esophagojejunostomy to reconstruct digestive tract.The perioperative indicators and complications of patients in the two groups were compared.Results The surgical time,time of esophagojejunostomy,and time to get out of bed after surgery of patients in the observation group were significantly shorter than those in the control group(P<0.05),the pain score 24 hours after surgery was significantly lower than that in the control group(P<0.05).There was no statistically significant difference between the two groups in terms of the incidence of complications or Clavien-Dindo grading(P>0.05).Conclusion Hand-sewn esophagojejunostomy for digestive tract reconstruction has a good clinical effect in gastric cancer during totally laparoscopic total gastrectomy.It can shorten the surgical time and time of esophagojejunostomy,reduce postoperative pain,and accelerate postoperative recovery,whose safety is comparable to Roux-en-Y esophagojejunostomy.

Aim To explore the effect of Danggui Shaoyao San on edema in rats with nephrotic syndrome and the underlying mechanism.Methods Rats were randomly divided into control group,model group,Danggui Shaoyao San group(17.2 g·kg-1·d-1),losartan group(30 mg·kg-1·d-1)and tolvaptan group(3 mg·kg-1·d-1).The rat model of nephrot-ic syndrome was established by tail vein injection of adriamycin.After four weeks of treatment,the levels of renal function and 24 h urinary protein were detected.The distribution of aquaporin 2(AQP2)and pS256-AQP2 in renal tissue was detected by immunohisto-chemistry.The levels of plasma arginine vasopressin(AVP)and angiotensin Ⅱ(Ang Ⅱ)were measured by radioimmunoassay.The expressions of renal AQP2,pS256-AQP2,angiotensin type 1 receptor(AT1R),arginine vasopressin receptor 2(V2R)protein and mRNA were measured by Western blot and RT-PCR,respectively.Results The three drugs could improve renal function,reduce proteinuria,decrease plasma AVP and Ang Ⅱ levels,and down-regulate AQP2 and pS256-AQP2 protein and mRNA expression in model rats.Danggui Shaoyao San and tolvaptan were more ef-fective than losartan in reducing plasma AVP levels.Conclusions Danggui Shaoyao San may regulate the expression of AQP2 by reducing the levels of AVP and Ang Ⅱ,and improve the edema of nephrotic syndrome rats.

Aim To investigate the protective effect of total flavonoids of Dracocephalum moldavica(TFDM)on atherosclerosis in rats and the inflammation of mouse macrophage RAW264.7 aggravated by trimeth-ylamine N-oxide(TMAO)and its possible mecha-nism.Methods The AS model of SD rats was estab-lished by high-fat diet feeding combined with intraper-itoneal injection of vitamin D3.The rats were divided into control group,model group,simvastatin group(15 mg·kg-1)and TFDM group(60,30,15 mg·kg-1).Biochemical method was used to detect the levels of se-rum total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C).HE staining was used to detect the pathological changes of aortic tissue.ELISA kit was used to detect the expression of TMAO,IL-1β,IL-6 in serum and TNF-α in liver tis-sue.Western blot was used to detect the expression of JAK,STAT and TNF-α protein in aorta.In addition,RAW264.7 macrophages were cultured in vitro,and LPS+TMAO was used to establish a macrophage in-flammation model,which was intervened by TFDM(100,50,25 mg·L-1).CCK-8 was used to determine cell viability and proliferation,and RT-qPCR was used to detect the expression of TNF-α,IL-6,JAK and STAT mRNA in cells.Results TFDM could significantly down-regulate the levels of serum TC,TG,LDL-C,ser-um TMAO,IL-1β,IL-6 and liver TNF-α,reduce aortic plaque deposition,and down-regulate the protein ex-pression of TNF-α,JAK and STAT in aorta.In addi-tion,TFDM intervention can significantly down-regulate the expression of TNF-α,IL-6,JAK,STAT mRNA and the expression of JAK,STAT protein.Conclusion TFDM can reduce the content of TMAO in serum,in-hibit JAK/STAT inflammatory signaling pathway and slow down the occurrence of inflammation,playing an anti-AS role.

Objectives:To develop a novel prediction model for mitral valve repair failure based on machine learning algorithms.Methods:Clinical and echocardiographic data were analyzed on patients,who underwent mitral valve repair in Fuwai Hospital from 2009 January 1st to 2022 December 31st.End points included immediate mitral valve repair failure (mitral replacement secondary to mitral repair failure) and recurrence regurgitation (moderate or severe mitral regurgitation before discharge).Risk factors of mitral valve repair failure were analyzed by XGBoost and shapley additive explanation (SHAP),and a machine learning model was established based on mixture of experts (MoE) as a risk prediction model and compared with conventional mitral valve repair complexity scores.Results:A total of 2314 patients were included in this study.Mitral repair was unsuccessful in 4.2％ (98 of 2314) of patients.Patient factors such as tricuspid regurgitation pressure gradient,A3 and A3P3 lesions,left ventricular end-systolic volume,and left atrium anterior and posterior diameter are associated with mitral valve repair failure;in addition,surgeon factors,such as cumulative repair failure rate,cumulative repair volume,and surgeon seniority,are also risk factors for mitral valve repair failure.The MoE model has an AUC value of 0.79,and the prediction performance is significantly better than traditional complexity scores.Conclusions:The MoE based machine learning model can predict the risk of mitral valve repair failure well.This evaluation system can effectively assist surgeons in assessing the risk of mitral valve repair failure and in selecting suitable treatment options for patients.

Objectives:To develop a novel prediction model for mitral valve repair failure based on machine learning algorithms.Methods:Clinical and echocardiographic data were analyzed on patients,who underwent mitral valve repair in Fuwai Hospital from 2009 January 1st to 2022 December 31st.End points included immediate mitral valve repair failure (mitral replacement secondary to mitral repair failure) and recurrence regurgitation (moderate or severe mitral regurgitation before discharge).Risk factors of mitral valve repair failure were analyzed by XGBoost and shapley additive explanation (SHAP),and a machine learning model was established based on mixture of experts (MoE) as a risk prediction model and compared with conventional mitral valve repair complexity scores.Results:A total of 2314 patients were included in this study.Mitral repair was unsuccessful in 4.2％ (98 of 2314) of patients.Patient factors such as tricuspid regurgitation pressure gradient,A3 and A3P3 lesions,left ventricular end-systolic volume,and left atrium anterior and posterior diameter are associated with mitral valve repair failure;in addition,surgeon factors,such as cumulative repair failure rate,cumulative repair volume,and surgeon seniority,are also risk factors for mitral valve repair failure.The MoE model has an AUC value of 0.79,and the prediction performance is significantly better than traditional complexity scores.Conclusions:The MoE based machine learning model can predict the risk of mitral valve repair failure well.This evaluation system can effectively assist surgeons in assessing the risk of mitral valve repair failure and in selecting suitable treatment options for patients.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

The PRR11 gene (Proline Rich 11) has been implicated in lung cancer; however, relationship between PRR11 and immune infiltration is not clearly understood. In this study, we used The Cancer Genome Atlas (TCGA) data to analyze the lung adenocarcinoma patients; PRR11 gene expression, clinicopathological findings, enrichment, and immune infiltration were also studied. PRR11 immune response expression assays in lung adenocarcinoma (LUAD) were performed using TIMER, and statistical analysis and visualization were conducted using R software. All data were verified using Gene Expression Profiling Interactive Analysis (GEPIA), and the Human Protein Atlas (HPA). We found that PRR11 was an important prognostic factor in patients with LUAD. PRR11 expression was correlated with tumor stage and progression. Gene Set Enrichment Analysis (GSEA) showed that PRR11 was enriched in the cell cycle regulatory pathways. Immune infiltration analysis revealed that the number of T helper 2 (Th2) cells increased when PRR11 was overexpressed. These results confirm the role of PRR11 as a prognostic marker of lung adenocarcinoma by controlling the cell cycle and influencing the immune system to facilitate lung cancer progression.
Humans ; Prognosis ; Adenocarcinoma of Lung/genetics* ; Lung Neoplasms/genetics* ; Biological Assay ; Cell Cycle