Objective To investigate the effect of Danshou decoction on autophagy,proliferation and apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.Methods HTR-8/Svneo cells were divided into control,Danshou decoction low-dose(Danshou decoction-L,100 μmol/mL),medium-dose(Danshou decoction-M,150 μmol/mL),high-dose(Danshou decoction-H,200 μmol/mL),the mTOR pathway activator MHY1485(100 nmol/mL),and Danshou decoction-H+M HY1485 groups.After 24 hours of treatment,cell proliferation,apoptosis,invasion,and migration were detected by using CCK-8,flow cytometry,Transwell,and wound healing assays.Autophagosome changes were observed,and the expres-sion levels of LC3,p62,Beclin1 mRNA and mTOR/S6K pathway related proteins were detected.Results Compared with the control group,the proliferation rate,invasion rate,migration rate,the proportions of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression reduced,and the apoptosis rate and p62 mRNA expression increased in Danshou decoction group at different dosages.The proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the MHY1485 group(all P＜0.05).Compared with the Danshou decoc-tion-H group,the proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the Danshou decoction-H+M HY1485 group(all P＜0.05).Conclusion Danshou decoction inhibits autophagy and proliferation,and induces apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.

Objective To explore the causal relationships of anxiety,depression and neuroticism with recurrent spontaneous abortion(RSA).Methods Genome-wide association study(GWAS)data were used to extract single nucleotide polymorphisms(SNPs)closely related to anxiety,depression and neuroticism as instrumental variables(IVs).Inverse variance weighting(IVW),weighted median estimator(WME),weighted mode(WM)and Mendelian randomization(MR)-Egger regression were employed for MR analysis to evaluate the causal effects of anxiety,depression and neuroticism with RSA,and to analyze heterogeneity,gene pleiotropy and sensitivity.Results A total of 46 SNPs were extracted from GWAS data as IVs(5 anxiety SNPs,9 depression SNPs,and 32 neuroticism SNPs).IVW,WME,WM and MR-Egger regression analysis revealed that the odds ratio(OR)and 95%confidence interval(CI)of anxiety data were 1.07(0.86-1.32),1.10(0.85-1.43),1.14(0.81-1.59)and 1.18(0.53-2.61);those of depression data were 1.11(0.93-1.32),1.05(0.83-1.32),0.96(0.67-1.38)and 0.57(0.25-1.31);those of neuroticism data were 1.01(0.75-1.36),1.07(0.73-1.56),1.02(0.49-2.12)and 2.40(0.46-12.44),but none of the above causal analyses were statistically significant(all P>0.05).After reliability analysis,the Cochran's Q test for heterogeneity evaluation was not significant(P>0.05),the MR-Egger regression intercepts for gene pleiotropy evaluation were all close to 0(P>0.05),and the sensitivity evaluation"Leave-one-out"test also shows that the combined causal effect values are similar.Conclusion There dose not exist causal relationships of anxiety,depression and neuroticism with RSA.The reliability test shows that the results are relatively robust.

Objective To investigate the effect of Danshou decoction on autophagy,proliferation and apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.Methods HTR-8/Svneo cells were divided into control,Danshou decoction low-dose(Danshou decoction-L,100 μmol/mL),medium-dose(Danshou decoction-M,150 μmol/mL),high-dose(Danshou decoction-H,200 μmol/mL),the mTOR pathway activator MHY1485(100 nmol/mL),and Danshou decoction-H+M HY1485 groups.After 24 hours of treatment,cell proliferation,apoptosis,invasion,and migration were detected by using CCK-8,flow cytometry,Transwell,and wound healing assays.Autophagosome changes were observed,and the expres-sion levels of LC3,p62,Beclin1 mRNA and mTOR/S6K pathway related proteins were detected.Results Compared with the control group,the proliferation rate,invasion rate,migration rate,the proportions of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression reduced,and the apoptosis rate and p62 mRNA expression increased in Danshou decoction group at different dosages.The proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the MHY1485 group(all P＜0.05).Compared with the Danshou decoc-tion-H group,the proliferation rate,invasion rate,migration rate,the proportion of autophagosomes/total cytoplasmic area,LC3,Beclin1 mRNA,p-mTOR/mTOR,and S6K protein expression increased,and the apoptosis rate and p62 mRNA expression decreased in the Danshou decoction-H+M HY1485 group(all P＜0.05).Conclusion Danshou decoction inhibits autophagy and proliferation,and induces apoptosis of human villous trophoblast cell HTR-8/Svneo by regulating the mTOR/S6K pathway.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Maintenance hemodialysis can improve many symptoms of patients with end-stage renal disease, but long-term dialysis can cause various physiological symptoms and psychological negative emotions. As a positive psychological change, post-traumatic growth plays a role in relieving patients' psychological pressure and reducing their pain. However, the post-traumatic growth of patients with maintenance hemodialysis needs to be improved. This article reviewed the status, influencing factors and interventions of post-traumatic growth in maintenance hemodialysis patients in order to provide reference for psychological care of such patients.

Objective:To understand the incidence of esophageal cancer in population at high risk in Yangzhong of Jiangsu province.Methods:Cluster random sampling method was conducted to select several natural villages from the high risk area of esophageal cancer in Yangzhong during 2011-2017. Local residents aged 40-69 years were selected as the target population and a total of 14 687 persons were diagnosed esophageal cancer by endoscopy and pathology.Results:Precancerous lesions were detected in 341 persons, with the detection rate as 2.32 % (341/14 687). Among them, there were 234 (1.59 %) cases with mild and 107 (0.73 %) cases with moderate esophageal hyperplasia. There were 77 positive cases with esophageal hyperplasia and the detection rate was 0.52 %. Among these positive cases, 41 showed severe esophageal hyperplasia/carcinoma in situ (0.28 %), with another 19 as early esophageal cancer (0.13 %) and 17 with invasive carcinoma (0.12 %). The overall early detection rate of positivity through active screening was 77.92 % (60/77), with trends of upwarding and then downwarding. The detection rate of esophageal lesions in men was higher than that in women ( P<0.05), but without significant gender specific differences seen in the detection rates of early esophageal cancer or invasive carcinoma ( P>0.05). The detection rates of all lesions other than invasive carcinoma, gradually increased with age ( P<0.05). The detection rate of invasive carcinoma reached the highest (0.39 %, 10/2 547) in the age group of 60-years and slightly decreased in the age group of 65-years old. Conclusions:Considerable numbers of patients with cancer and precancerous lesions in groups at high-risk can be found through the screening program for esophageal cancer, suggesting that the screening program is of great significance in improving the survival rate and quality of life. Attention should be paid to men, with elderly groups in particular, at high-risk in order to increase the detection rate of early cases.

Objective To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods From 2009 to 2015, 31 natural villages with high?incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub?district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost?effectiveness analysis and cost?benefit analysis, were performed to evaluate the current screening schemes. Results The mean age of all respondents were (53.60 ± 8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high?grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness?cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods From 2009 to 2015, 31 natural villages with high?incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub?district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost?effectiveness analysis and cost?benefit analysis, were performed to evaluate the current screening schemes. Results The mean age of all respondents were (53.60 ± 8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high?grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness?cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Objective To study the characteristics of hyperphenylalaninemia (HPA) and the differences in blood and urine metabolic index and their correlation.Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department,Guangdong Women and Children's Hospital,Guangzhou Medical University from January 2014 to June 2017,were enrolled.Tandem mass spectrometry (MS/MS),gas chromatography/ mass spectrometry (GC-MS) and high performance liquid chromatography (HPLC) were used to analyze the concentration of blood and urine metabolites in children,and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin (BH4) and dihydrobiopterindine reductase (DHPR) deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed.Results Among the 137 cases of HPA,there were 101 cases (73.7％) of phenylalanine hydroxylase deficiency (PAH),and among them 21 cases (15.3％) were classic phenylketonuria (PKU),37 cases were mild PKU (27.0％),43 cases (31.4％) wcrc mild HPA.Thcrc were 22 cases (16.1％) with BH4 reaction,and 79 cases (57.7％) of non-reactive type.Besides,there were 36 cases (26.3％) of tetrahydrobiopterin deficiency (BH4 D),of which 6-pyruvoyl tetrahydropterin synthase deficiency (PTPS) in 34 cases (24.8％) and dihydrobiopterindine reductase deficiency (DHPR) in 2 cases (1.5％).Urinary phenylacetic acid (r =0.673,P ＜ 0.01),phenyllactic acid (r =0.736,P ＜ 0.01),phenylpyruvic acid (r =0.642,P ＜ 0.01) were significantly correlated with blood phenylalanine (Phe) concentration,and the neopterin (N) (r =0.442,P ＜ 0.01) and biopterin (B) (r =0.398,P ＜ 0.01) had low correlation.Urinary phenylacetic acid,phenyllactic acid and phenylpyruvic acid had no correlation with urinary pterin.There were significant differences among PTPS deficiency group,BH4 response type,and non-reactive type(all P ＜ 0.05),but no significant difference between the BH4 reaction type and the non-reactive group (P ＞ 0.05).Conclusions Through the analysis of the different types of HPA metabolic profiles,it can help to master the incidence and characteristics in the region,within a certain concentration range of blood Phe,the phenylacetic acid,phenyllactic acid,phenylpyruvic acid should not be tested by GC-MS alone.Uterine erythropoietin analysis of BH4D classification and identification of BH4 reaction,non-reactive PKU have a supporting role,so master the metabolic index of various types of concentration and relevance of HPA,it can provide basis for early diagnosis,accurate treatment and follow-up.