BACKGROUND: Bile acids (BAs) facilitate the progression of gastric intestinal metaplasia (GIM). Long non-coding RNAs (lncRNAs) dysregulation was observed along with the initiation of gastric cancer. However, how lncRNAs function in GIM remains unclear. This study aimed to explore the role and mechanism of lncRNA PVT1 in GIM, and provide a potential therapeutic target for GIM treatment. METHODS: We employed RNA sequencing (RNA-seq) to screen dysregulated lncRNAs in gastric epithelial cells after BA treatment. Bioinformatics analysis was conducted to reveal the regulatory mechanism. PVT1 expression was detected in 21 paired biopsies obtained under endoscopy. Overexpressed and knockdown cell models were established to explore gene functions in GIM. Molecular interactions were validated by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (Ch-IP). The levels of relative molecular expression were detected in GIM tissues. RESULTS: We confirmed that lncRNA PVT1 was upregulated in BA-induced GIM model. PVT1 promoted the expression of intestinal markers such as CDX2 , KLF4 , and HNF4α . Bioinformatics analysis revealed that miR-34b-5p was a putative target of PVT1 . miR-34b-5p mimics increased CDX2 , KLF4 , and HNF4α levels. Restoration of miR-34b-5p decreased the pro-metaplastic effect of PVT1 . The interactions between PVT1 , miR-34b-5p, and the downstream target HNF4α were validated. Moreover, HNF4α could transcriptionally activated PVT1 , sustaining the GIM phenotype. Finally, the activation of the PVT1 /miR-34b-5p/ HNF4α loop was detected in GIM tissues. CONCLUSIONS BAs facilitate GIM partially via a PVT1/miR-34b-5p/HNF4α positive feedback loop. PVT1 may become a novel target for blocking the continuous development of GIM and preventing the initiation of gastric cancer in patients with bile reflux.
Humans ; RNA, Long Noncoding/metabolism* ; MicroRNAs/metabolism* ; Hepatocyte Nuclear Factor 4/genetics* ; Bile Acids and Salts ; Kruppel-Like Factor 4 ; Metaplasia/metabolism*

Rheumatoid arthritis (RA) is an autoimmune disease with a complex etiology. Monocyte-derived macrophages (MDMs) infiltration are associated with RA severity. We have reported the deletion of G-protein-coupled receptor kinase 2 (GRK2) reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling. However, as more GRK2-interacting proteins were discovered, the GRK2 interactome mechanisms in RA have been understudied. Thus, in the collagen-induced arthritis mouse model, we performed genetic GRK2 deletion using GRK2^f/fLyz2-Cre^+/- mice. Synovial inflammation and M1 polarization were improved in GRK2^f/fLyz2-Cre^+/- mice. Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptor γ (PPARγ) as a new GRK2-interacting protein. We further confirmed that fms-related tyrosine kinase 1 (Flt-1), which promoted macrophage migration to induce angiogenesis, was inhibited by GRK2-PPARγ signaling. Mechanistically, excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγ ligand-binding domain and enhanced Flt-1 transcription. Furthermore, the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology, Flt-1⁺ macrophages induced-synovial inflammation, and angiogenesis. Altogether, we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling. Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration, affording a distinct way to control joint inflammation and angiogenesis of RA.

The key measure to effectively alleviate the risks and economic burden of chronic diseases is to pro-mote the integration of medical and preventive measures in the management of chronic diseases.As the top of medi-cal service technology,public hospitals play an indispensable role in chronic disease management.Analyzing the problems of public hospitals participating in the integration of chronic disease management and medical prevention,it is believed that the main reason restricting public hospitals'participation in the integration of medical prevention is the lack of endogenous motivation caused by the imperfect compensation mechanism.Exploring the compensation mechanism for chronic disease management suitable for the development environment of public hospitals from the perspective of medical prevention integration.

Objective:To understand the degree of professional autonomy of nurses in Pediatric Nursing Alliance and the status of pediatric nursing practice environment, which providing guidance for the development of a series of specialized training in the alliance.Methods:Stratified random sampling method was used to conduct a questionnaire survey on nursing staff of different professional levels in Pediatric Nursing Alliance, which through the questionnaire star by using the questionnaire general information and training demand questionnaire, nurses practice professional autonomy scale, pediatric nursing staff structural empowerment questionnaire and nursing practice influencing factors questionnaire through the questionnaire star.Results:The total score for professional autonomy of nurses in the pediatric alliance was 192.66±18.63, the structural empowerment ( OR=1.137, 95% CI=1.084-1.194), lack of caring team ( OR=2.763, 95% CI=1.443-5.292) and performance evaluation ( OR=0.498, 95% CI= 0.274-0.908), specialized education and professional experience ( OR=0.548, 95% CI= 0.334-0.871) were affecting the clinical nursing practice. Conclusion:The degree of professional autonomy of nurses in the Pediatric Nursing Alliance is in the middle and high level. Key factors affecting nursing practice including insufficient structural empowerment, lack of opportunities to continue learning, lack of nursing teams, lack of effectiveness evaluation and the lack of specialized education and work experience, which guiding the pediatric nursing alliance to continuously deepen the connotation of pediatric nursing professional and innovative team collaboration new model, utilize the advantages of resources to actively cultivate specialized nursing research personnel, carry out multi-disciplinary and cross-disciplinary cooperation, improve the nursing quality evaluation index system, so as to enhance the professional nursing service capacity and value.

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ² test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ²=288.60,P<0.01),N stage(χ²=68.10, P<0.01), vascular invasion(χ²=128.70, P<0.01)and neural invasion(χ²=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ²=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Objective To investigate certified specialized nurses' willingness in building an reappraisal system and to provide a basis for further completing the appraisal system and criteria for specialized nurses, defining their roles, and encouraging them to play their leading roles in clinical work.Methods Totally 250 certified specialized nurses from 8 Class Ⅲ hospitals in Beijing were selected by convenient sampling and investigated with the self-designed questionnaire. The subjects' willingness in building the reappraisal system and criteria were analyzed.Results In terms of the 240 specialized nurses' wiliness in building the reappraisal system, their scores in clinical competence, teaching ability and research capability were (13.14±3.86), (13.60±2.27) and (9.50±2.94), respectively. There was statistical difference in the willingness in building the evaluation criteria of clinical competence between specialized nurses with different length of service and titles (P<0.05); there was also statistical difference in the willingness in building the evaluation criteria of teaching ability between specialized nurses with different educational background (P<0.05).Conclusions The specialized nurses' willingness in building the reappraisal indicators. Nursing managers shall train specialized nurses based on their shortcomings, build stricter criteria for future training for specialized nurses, and encourage the nursing team to become expert nurses.

OBJECTIVE:To prepare the lurasidone hydrochloride solid dispersion,and improve its dissolution rate. METH-ODS:Taking povidone K30 as the carrier,solvent method was used to prepare the lurasidone hydrochloride solid dispersion with different drug-load ratios(1:0.5,1:1,1:2). The in vitro dissolution rates of 3 kinds of lurasidone hydrochloride solid dispersion with physical mixture (lurasidone hydrochloride-povidone K30) and original preparation were compared. X-ray powder diffraction method was adopted to analyze the crystal structures of raw material of lurasidone hydrochloride,povidone K30 and accessories, physical mixture (1:2) and accessories,and lurasidone hydrochloride solid dispersion (1:2) and accessories. RESULTS:Com-pared with physical mixture,the dissolution rate of lurasidone hydrochloride solid dispersion with drug-load ratios of 1:0.5,1:1, 1:2 was significantly improved,and the dissolution rate of solid dispersion was increased as the increase of the carrier ratio. The in vitro dissolution rates of lurasidone hydrochloride solid dispersion with drug-load ratio of 1:2 and original preparation were respec-tively 101.2%and 100.2%in 20 min. X-ray powder diffraction showed,there were characteristic absorption peaks of lurasidone hy-drochloride and accessories in physical mixture;the characteristic absorption peak of lurasidone hydrochloride in solid dispersion disappeared basically,and the characteristic absorption peak of accessories still existed. CONCLUSIONS:The in vitro dissolution of lurasidone hydrochloride solid dispersion with drug-load ratio of 1:2 is similar to original preparation,and lurasidone hydrochlo-ride exists in the solid dispersion as amorphous form.

Objective To summarize the puncture indications and the pathological type features of renal allografts biopsies in our center for evaluating its safety and diagnostic value .Methods The data of 773 percutaneous renal allograft biopsies in 629 kid‐ney transplants in the Pearl River Hospital of Southern Medical University from January 2005 to June 2014 were retrospectively an‐alyzed .Results The success rate of renal biopsy was 100% ,9 cases(1 .2% ) were complicated postoperative perirenal small hemato‐ma ,33 cases(4 .3% ) with gross hematuria and 1 case(0 .13% )with abdominal pain .Among the indications of 773 biopsies ,protein urine occured 205 cases(26 .5% ) of patient ,blood Cr increased in 187 cases(24 .2% )of patients ,protein urine simultaneously com‐plicating blood Cr increased ,in 313 cases of patients ,53 cases(6 .9% )had postoperative oliguria urinary ,and 15 cases(1 .9% )were get procedural biopsy .In the pathological types ,21 cases(2 .7% ) were normal ,179 cases (23 .2% ) were acute T cell‐mediated rejec‐tion after transplantation ,51 cases (6 .6% )were acute antibody‐mediated rejection ,205 cases (26 .5% ) were chronic T cell‐mediated rejection and 43 cases(5 .6% ) were chronic antibody‐mediated rejection;41 cases(5 .3% ) were drug toxicity ,29 cases(3 .7% ) were acute tubular necrosis(ATN) ,11 cases(1 .4% ) were relapsed or new nephropathy ;9 cases(1 .2% )were HBV related renal disease;39 cases (5 .0% ) were critical lesion and 145 cases(18 .8% )were others .Conclusion Rrenal allograft biopsy is safe ,it is important to the etiological diagnosis of renal disease after renal transplant ,which can guide the clinical treatment and improve the long term survival of renal graft and should be routinely carried out in clinic .

Background and objective Cetuximab is a monoclonal antibody directed against epidermal growth fac-tor receptor. Emerging evidence showed improved effcacy with the addition of cetuximab to chemotherapy in advanced non-small cell lung cancer (NSCLC), but the data in oriental population are limited. hTe aim of this study is to investigate the eff-cacy of cetuximab in combination with chemotherapy in Chinese patients with advanced NSCLC.Methods NSCLC patients receiving cetuximab in combination with chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were enrolled and retrospectively analyzed. Clinical characteristic, effcacy, outcome and toxicity data were analyzed.Results A total of 40 patients were enrolled into this study in which 29 were male, 36 with adenocarcinoma. In the 23 patients who had received palliative chemotherapy previously (with a median of 2 prior chemotherapy regimens), the median progression-free survival (PFS) atfer the last prior chemotherapy regimen was 2.3 months. For the overall population, 13 (32.5%) patients achieved partial response atfer cetuximab in combination with chemotherapy. Response rate were 52.9% (9/17) and 17.4% (4/23) in chemotherapy-naive patients and chemotherapy-treated patients, respectively (P=0.018). hTe median PFS was 4.8 months for the overall population. In chemotherapy-naive patients and chemotherapy-treated patients, the median PFS was 8.4 months and 4.1 months, respectively (P=0.062). hTe estimated median overall survival was 17.1 months. Toxicities were generally manageable and no treatment-related deaths occurred.Conclusion Cetuximab in addition to che-motherapy appears to be associated with promising effcacy and acceptable toxicity proifle in Chinese patients with advanced NSCLC. Further validation is needed.

Objective To observe the expression of MicroRNA-21(miRNA-21)in kidney tissue of unilateral ureteral obstruc-tion (UUO)rats and explore mechanisms of miRNA-21 involved in TGF-β1/Smad3 signaling pathway in renal interstitial fibrosis (RIF).Methods Totally 20 adult male SD rats were divided into UUO group and Sham operation group.The left ureter of rats in UUO group were ligated,and the rats in sham group were dissociated left ureter only,but not to be obstructed.The left kidney tis-sue was collected at the 3rd、7th days after surgery.Real-time quantitative PCR analysed the expression of miRNA-21.Masson stai-ning,HE staining and immunohislochemistry staining were used to evaluate the degree of RIF.The expression of transforming growth factor-β1(TGF-β1)、Smad3,α-smooth muscle actin (α-SMA)、and collagenⅠ(Col-Ⅰ)were examined by immunohislochemis-try staining.Results The expression of miRNA-21 in kidney tissue was higher at 3rd、7th days after surgery in UUO groups than that in Sham group(P <0.01).The expression in UUO group at 7th day was higher than 3rd day after surgery(P <0.01).The fi-brosis score,positive TGF-β1、Smad3、Col-Ⅰ、α-SMA area in UUO group were significantly higher than those of Sham group at 3rd、7th days (P <0.01),Which at 7th day were higher than 3rd day in UUO group(P <0.01).The expressions of miRNA-21 in kidney tissue was positive correlations with the fibrosis score(r=0.888,P <0.01).The expressions of miRNA-21 in kidney tissue was positive correlations with TGF-β1、Smad3、Col-Ⅰ、α-SMA(r=0.799,0.849,0.882,0.896,P <0.01).Conclusion The expres-sion of miRNA-21 was upregulated in UUO kidney tissue after model establishment.The RIF degree might be positive correlations with miRNA-21 expression,and TGF-β1/Smad3 signaling pathway positively regulate miRNA-21 to mediate rats RIF.