Objective:To explore the effect of sacubitril/valsartan(LCZ696)on intestinal microbiota and serological parameters associ-ated with its derived metabolites in rats with right ventricular remodeling due to hypoxic pulmonary hypertension(HPH).Methods:A total of 24 male rats were randomly divided into Control group,Hypoxia group,and H-LCZ696 group.Since day 1,the rats in the H-LCZ696 group were given LCZ696 by gavage,while those in the other two groups were given normal saline by gavage,both for 4 con-secutive weeks.Related indicators were measured after experiment,including hemodynamics,color Doppler ultrasound of right heart,and right ventricular remodeling.Histopathological staining and transmission electron microscopy were used to observe tissue struc-tures;the metagenomics technique was used to analyze the characteristics and functional annotation of intestinal microbiota in the fe-ces of the rats;ELISA was used to measure the serological parameters of the metabolites derived from intestinal microbiota.Results:There was a significant difference in mean pulmonary arterial pressure(mPAP)between the three groups of rats(F=101.797,P=0.000).Compared with the Control group,the Hypoxia group had an increase in mPAP,a reduction in right ventricular function,and in-creases in the indicators for pulmonary vascular remodeling and right ventricular remodeling.Compared with the Hypoxia group,the H-LCZ696 group had a reduction in mPAP,an improvement in right ventricular function,and reductions in the indicators for pul-monary vascular remodeling and right ventricular remodeling.Trans-mission electron microscopy showed that the Hypoxia group had disordered myocardial myofibrils of the right ventricle and mitochon-drial swelling,while such ultrastructural damage was improved after LCZ696 intervention.The metagenomics analysis showed that the Hypoxia group had a reduction in the diversity of intestinal microbiota,with increases in the abundance of pathogenic bacteria(such as Proteobacteria,Prevotella,and Clostridium)and reductions in the abundance of probiotic bacteria(such as Lachnospiraceae and Lacto-bacillus),and such changes were partially reversed after LCZ696 intervention,with inhibition of the proliferation of pathogenic bacteria such as Clostridiales,the failure to restore the diversity of intestinal microbiota,and a further reduction in the abundance of some probi-otic bacteria(such as Lactobacillus).ELISA showed that compared with the Control group,the Hypoxia group had increases in the serum levels of pro-inflammatory metabolites,and compared with the Hypoxia group,the H-LCZ696 group had reductions in the se-rum levels of pro-inflammatory metabolites.Conclusion:LCZ696 can alleviate right ventricular remodeling in HPH and regulate pathogenic bacteria and serum pro-inflammatory metabolites,with a main therapeutic effect on the cardiovascular system and a regula-tory effect on intestinal microbiota.

Objective:To investigate the effect of trastuzumab deruxtecan (T-DXd) in the treatment of metastatic breast cancer (MBC) patients with different expression levels of human epidermal growth factor receptor 2 (HER2) and the influencing factors of prognosis.Methods:The retrospective case series analysis and cohort study were conducted. Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd. The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results:All 20 patients were female, with a median age [ M ( Q1, Q3)] of 49 years old (40 years old, 58 years old). Of the 20 cases, 12 had low expression of HER2 [immunohistochemistry HER2+, or immunohistochemistry ++ and fluorescence in situ hybridization (FISH)-negative], and 8 had overexpression of HER2 (immunohistochemistry HER2+++, or immunohistochemistry ++ and FISH-positive); median number of lines of treatment with T-DXd was 6 lines (3 lines, 7 lines); 14 patients had partial remission, 3 patients had stable disease, and 3 patients had disease progression, with an objective remission rate (ORR) of 70% (14/20) and a disease control rate of 85% (17/20). Eight patients with overexpression of HER2 had objective remission in 6 cases, and 12 patients with low expression of HER2 had objective remission in 8 cases, and the ORR difference between the two groups was not statistically significant ( P = 1.000). The main adverse reactions of the patients were nausea (14 cases), vomiting (12 cases), leukopenia (10 cases), elevated aspartate aminotransferase (10 cases), elevated alanine aminotransferase (9 cases), anemia (8 cases), fatigue (8 cases), alopecia (8 cases), neutropenia (6 cases), and thrombocytopenia (5 cases); ≥ grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions, all with an incidence of ≤10%. The median follow-up time was 7.1 months (1.9 months, 11.5 months). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.9-9.1 months), and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2 [7.0 months (95% CI: 6.4- 7.6 months) vs. 4.0 months (95% CI: 1.7-6.3 months)], and the difference in PFS between the two groups was statistically significant ( P = 0.025). Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd ( HR = 0.265, 95% CI: 0.075-0.945, P = 0.041). Conclusions:MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd. The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd, and may serve as a biomarker for predicting PFS in such patients, but it may not affect the ORR.

ObjectiveTo explore the relationship between occupational stress， psychological capital and insomnia among nurses， and to test the mediating effect of psychological capital on the relationship between nurses' occupational stress and insomnia. MethodsStratified random sampling method was utilized in selecting 810 nurses from a tertiary A-level hospital from March to May 2021. The Effort-Reward Imbalance questionnaire （ERI）， Psychological Capital Questionnaire （PCQ） and Athens Insomnia Scale （AIS） were used to evaluate the occupational stress， psychological capital and insomnia of nurses， respectively. Then the mediation effect of psychological capital on the relationship between occupational stress and insomnia in nurses was tested by PROCESS macro program. ResultsA total of 658 （81.23%） questionnaires were effectively collected. Analysis found that nurses' effort-reward ratio was positively correlated with AIS score （r=0.379， P<0.01）， and negatively correlated with PCQ score （r=-0.275， P<0.01）. Nurses' PCQ score was negatively correlated with AIS score （r=-0.402， P<0.01）. Nurses' occupational stress could negatively predict psychological capital （β=-11.024， t=-7.324， P<0.01）， and positively predict insomnia （β=4.117， t=10.478， P<0.01）. Psychological capital could negatively predict insomnia （β=-0.087， t=-9.083， P<0.01）. The predictive effect of occupational stress on insomnia was statistically significant with psychological capital introduced as a mediating variable （β=3.158， t=8.185， P<0.01）. ConclusionPsychological capital plays a partial mediating role in the relationship between occupational stress and insomnia in nurses.

To explore the influencing factors of perceived stress among frontline nurses during COVID-19, and the role of positive psychological capital in anxiety sensitivity and stress perception, so as to provide evidence for reducing the perceived stress of frontline nurses. From December 2021 to January 2022, 475 frontline nurses from 8 hospitals in X city were investigated by general data questionnaire, positive psychological capital, anxiety sensitivity index and perceived stress scale. The results showed that there were significant differences in nurses’ perceived stress in age, working years, professional title and salary. Perceived stress was positively correlated with anxiety sensitivity, negatively correlated with positive psychological capital, and anxiety sensitivity was negatively correlated with positive psychological capital. Anxiety sensitivity can not only directly predict perceived stress, but also negatively affect perceived stress through positive psychological capital. Therefore, during the epidemic prevention and control in COVID-19, nurses can obtain effective stress coping strategies by strengthening their positive psychological capital, thus reducing their anxiety and perceived stress, and better providing high-quality nursing services for patients.

OBJECTIVE: Endometrial cancer (EC) is a common gynecologic cancer worldwide. However, the pathogenesis of EC has not been epigenetically elucidated. Here, this study aims to describe the DNA methylation profile and identify favorable gene signatures highly associated with aberrant DNA methylation changes in EC. METHODS: The data regarding DNA methylation and gene expression were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially methylated CpG sites (DMCs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs) were identified, and the relationship between the 2 omics was further analyzed. In addition, weighted CpG site co-methylation network (WCCN) was constructed followed by an integrated analysis of DNA methylation and gene expression data. RESULTS: Four hundred thirty-one tumor tissues and 46 tissues adjacent tumor of EC patients were analyzed. One thousand one hundred thirty-five DMCs (merging to 10 DMRs), and 1,488 DEGs were obtained between tumor and normal groups, respectively. One hundred forty-eight DMCs-DEGs correlated pairs and 13 regional DMCs-DEGs pairs were obtained. Interestingly, we found that some hub genes in 2 modules among 8 modules of WCCN analysis were down-regulated in tumor samples. Furthermore, protocadherins (PCDHs) clusters, DDP6, TNXB, and ZNF154 were identified as novel deregulated genes with altered methylation in EC. CONCLUSION: Based on the analysis of DNA methylation in a systematic view, the potential long-range epigenetic silencing (LRES) composed of PCDHs was reported in ECs for the first time. PCDHs clusters, DDP6, and TNXB were firstly found to be associated with tumorigenesis, and may be novel candidate biomarkers for EC.
Biomarkers ; Carcinogenesis ; DNA Methylation* ; DNA* ; Endometrial Neoplasms* ; Epigenomics ; Female ; Gene Expression* ; Genome ; Humans ; Methylation

OBJECTIVE:To observe the effectiveness and safety of Jin's three-needle combined with Jiawei wumei pill in the treatment of menopausal insomnia.METHODS:One hundred and sixty-five patients with perimenopausal insomnia were selected from our hospital during Jan.2015-Mar.2016,and then divided into group A (n=41),group B (n=41),group C (n=41) and group D (n=42) according to random number table.Group A was given Estazolam tablet 1 mg,qd;group B was given Jin's three-needle 30 min/time,qd;group C was given Jiawei wumei pill,one pill,after breakfast and supper warm taking;group D was given Jin's three-needle combined with Jiawei wumei pill with same usage as group C.Four groups were treated for 4 weeks.PSQI score,modified Kupperman score,life quality score,serum levels of E2 and FSH were observed in 4 groups before and after treatment,and the occurrence of ADR was recorded.RESULTS:Before treatment,there was no statistical significance in above score (P＞0.05).After treatment,PSQI score and modified Kupperman score of 4 groups were decreased significantly,compared to before treatment;the group B,C,D were significantly lower than the group A;the group D was significantly lower the group B,C,with statistical significance (P＜0.05).The life quality score of 4 groups were increased significantly,and the group B,C,D were significantly higher than the group A;the group D was significantly higher than the group B,C,with statistical signifi cance (P＜0.05).E2 level of group B,C,D were significantly increased,while FSH level was decreased significantly,the improvement of group D was significantly better than group B,C;the improvement of group D was significantly better than that of group B,C,with statistical significance (P＜0.05).The incidence of ADR in group A was significantly higher than group B,C,D,with statistical significance (P＜0.01),and there was no statistical significance in the incidence of ADR among group B,C,D,with statistical significance (P＞0.05).CONCLUSIONS:Jin's three needle combined with Jiawei wumei pill is effective in the treatment of perimenopausal insomnia with good safety.

Objective To assess the expression and significance of proprotein convertase subtilisin kexin 9 (PCSK9) in patients with rheumatoid arthritis (RA).Methods Sixty-five RA patients and forty-seven healthy controls were recruited in this study.The body mass index (BMI) and serum total cholesterol (TC),triglyceride (TG),high density lipoprotein (HDL),lipoprotein a,low density lipoprotein (LDL),very low density lipoprotein(VLDL),apolipoprotein A (ApoA),apolipoprotein B (ApoB) and the ratio of LDL-C/HDL-C were tested.Other parameters included disease activity score 28 (DAS28),rheumatoid factor (RF),anti-cyclic citrullinated peptide (CCP) antibody,erythrocyte sedimentation rate (ESR),c-reactive protein (CRP).Serum PCSK9 level was measured by ELISA and compared between RA patients and healthy controls.Results (1) The serum PCSK9 levels in RA patients were higher than those in healthy controls [(409.36 ±223.52) μg/L vs (292.19 ± 109.79) μg/L,P ＜ 0.05].(2) Compared with subgroup of moderate and low active disease and patients in remission,PCSK9 was significantly higher in patients with highly active disease (P ＜ 0.05).(3) The serum PCSK9 levels were positively correlated with RF,TC,TG,LDL,very low density lipoprotein (VLDL),ApoB,with r values as 0.303,0.490,0.320,0.451,0.319,0.463,respectively (P ＜ 0.05).(4) Multiple stepwise regression analysis showed that DAS28,RF,TC and LDL-C/HDL-C were relevant factors for PCSK9 in RA patients.Conclusions The serum PCSK9 level is elevated in RA patients,which is related to RF,disease activity,TC,TG,LDL,VLDL,ApoB.This suggests that PCSK9 is potentially linked to inflammatory reaction and lipid metabolism in rheumatoid arthritis.

Objective To study changes in serum homocysteine(Hcy) and its correlation with serum levels of folic acid and high sensitivity C-reactive protein(hs-CRP)in Tibetan patients with mildto-moderate Alzheimer's disease at various high altitude areas,so as to direct the clinical diagnosis and treatment of AD in plateau hypoxia environment Method 108 cases were divided into four groups:23 AD Tibetan patients at middle altitude(AD/middle altitude group)and 23 healthy Tibetan subjects (healthy/middle altitude group) in Qinghai-Tibet Plateau Xining region,altitude at 2,260 m,31 AD Tibetan patients (AD/high altitude group)and 31 healthy Tibetan elderly subjects (healthy/high altitude group)in Yushu region at altitude of 3,800 m.Among the total study subjects,half are males,aged from 60 to 85 years.The levels of serum Hcy,Vitamin B12 and folic acid(FA)were measured by the Fluorescence Polarization Immunoassay(FPIA).Serum hs-CRP,triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)were measured by automatic biochemistry analyzer.Correlation of Hcy with FA and hs-CRP was analyzed.Result Both high altitude and middle altitude group showed the levels of Hcy and hs-CRP were significantly higher in AD Tibetan patients than in healthy control at the same altitude(allP＜0.05).The levels of Hcy,LDL-C and hs-CRP of subjects were higherat high altitude than at middle altitude(P＜0.05).In contrast,folic acid levels in AD and control groups were lower at the high altitude than at middle altitude(P＜0.05).The levels of vitamin B12 and TG were not significantly different among all four groups.Multiple logistic regression analysis showed that altitude,folacin and hs-CRP were the risk factors for Hcy in patients with AD at plateau(OR =0.351,2.794,3.021,P=0.045,0.037,0.016).Conclusion Along with increased altitude,serum level of Hcy is significantly increased in AD Tibetan patients living in high altitude area.High altitude,high hs-CRP and lower folacin may be the risk factors for hyper-homocysteine in AD Tibetan patients with high altitude,and their combined effects are involved in the occurrence and development of AD.

OBJECTIVE:To evaluate the effect of clinical antibiotics use special rectification in our hospital. METHODS:100 discharged medical records of typeⅠincision surgery were randomly sampled from our hospital during May in 2010 to Apr. in 2011,May in 2011 to Apr. in 2012,May in 2012 to Apr. in 2013,May in 2013 to Apr. in 2014,totaling 400 records. And then evaluation indicators were analyzed statistically,such as antibiotics use intensity,perioperative DDDs of antibiotics in typeⅠinci-sion surgery,DUI,types of antibiotics during perioperative period,medication time,etc. RESULTS:Since the implementation of clinical antibiotics use special rectification in May 2011,the utilization ratio of antibiotics in typeⅠincision surgery of our hospital decreased from 96% to 33%;DUI decreased from 1.44 to 0.79;while reasonable rate of drug selection increased from 19.8% to 100%,and that of medication time increased from 43.8% to 100%. CONCLUSIONS:Rational medication evaluation indicators in typeⅠincision surgery of our hospital have been improved after the implementation of clinical antibiotics use special rectification.

Objective To discuss CT,MR and~1H-MRS features of central neurocytoma(CNC).Methods Imaging findings ofneurocytomas in 7 cases confirmed by pathology were retrospectively analyzed with literature review.2 cases were examined by CT、MR and~1 H-MRS,2 cases only by MR,and 3 cases only by CT.Results All the tumors were located in the lateral ventricles.There were different degree hydrocephalus in all cases.The masses were heterogeneous appearance on CT with necrotic area and fine to course calcifications.Heterogeneous enhancement was seen in the solid portion.The tumors were isointense and hypointense on T_1WI and heterogeneous on T_2WI.Heterogeneous enhancement was also seen on MRI.The in vivo~1H-MRS showed prominent choline(Cho) and low N-acetyl aspartate(NAA) compared to the normal.Conclusion Central neurocytoma should be considered when a tumor was located at the lateral ventricles especially septum pellucidum in young patients.CT,MR and~1H-MRS are helpful in making a preoperative diagnosis.