Effects of miR-214 on the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts by targeting sex determining region Y-box 4 / 中华风湿病学杂志

Objective:To investigate the effect of miR-214 targeting sex determining region Y-box 4 (SOX4) on the proliferation and apoptosis of rheumatoid arthritis (RA) synovial fibroblasts.Methods:Synovial tissue samples from 45 patients with rheumatoid arthritis and 30 patients with joint trauma who underwent joint replacement surgery from 2017 to 2019 in Shangqiu First People's Hospital samples were collected. The expression levels of miR-214 and SOX4 in synovial tissues were detected by real time quantitative polymerase chain reaction (RT-qPCR); The expression levels of serum rheumatoid factor (RF) and C-reactive protein (CRP) were detected by enzyme-linked immunosorbent assay (ELISA) test. The correlation between miR-214 or SOX4 and RF, CRP, erythrocyte sedimentation rate (ESR) was tested by Pearson's analysis. Human fibroblast-like synoviocytes (HFLS)-RA cells were derived from the control group, miR-214 mimic group, mimic-NC group and miR-214 mimic+pcDNA3.1-SOX4 group and se-parated by Lipofectamine 3 000. The cell viability of each group was detected by CCK8, the apoptosis of each group was detected by flow cytometry, the target relationship was verified by dual luciferase experiment, Western-blot was used to detect the protein expression levels of related indicators. Independent sample t test was used for the comparison between the two groups, one-way nalysis of variance (ANOVA) was used for multi-group comparison, and LSD- t test was used for the comparison between the two groups. Results:Compared with the control group (4.6±0.7, 1.9±0.7) and HFLS cells (1.00±0.06, 1.00±0.09), miR-214 was expressed lower in RA tissues (2.6±0.9) and HFLS-RA (0.30±0.05) ( t=10.026, P<0.05; t=15.815, P<0.05). Compared with SOX4 was highly expressed in RA tissues (4.6±0.9) and HFLS-RA cells (3.89±0.41) ( t=14.772, P<0.05; t=12.020, P<0.05). Serum RF, ESR and CRP expression levels in RA group [(46±7) U/ml, (46.4±9.6) mm/1 h, (34.8±9.8) mg/ml] were signifi-cantly higherthan those in the control group [(16±4) U/ml, (9.2±2.0) mm/1 h, (2.1±0.7) mg/ml] ( t=22.906, P<0.05; t=25.338, P<0.05; t=22.314, P<0.05). miR-214 was negatively correlated with serum RF, CRP and ESR was negatively correlated with miRNA( r=-0.574, P<0.05; r=-0.448, P<0.05; r=-0.549, P<0.05), while was positively correlated with SOX4 ( r=0.492, P<0.05; r=0.369, P<0.05; r=0.325, P<0.05). Compared with the control group and the mimic-NC group, cell viability, Ki-67 and p-p65 protein expression decreased significantly after miR-214 mimic transfection for 24 h ( F24 h=16.980, P<0.05;, F48 h=42.735, P<0.05; F72 h=164.448, P<0.05; FKi-67=290.112, P<0.05; Fp-p65/p65=223.548, P<0.05), while the apoptosis rate and Bax protein expression increased significantly ( F=344.360, P<0.05; F=106.376, P<0.05). Overexpression of SOX4, reverses the effect of miR-214. Conclusion:miR-214 targets SOX4 to inhibit the proliferation of synovial fibroblasts and promote apoptosis in rheumatoid arthritis. This may relate to the inhibition of NF-κB signaling pathway by miR-214.

Risk factors of urinary incontinence in Chinese women based on random forest / 中华妇产科杂志

Objective:To explore the risk factors of urinary incontinence (UI) in China by using random forest algorithm, and to evaluate the predictive effect of each risk factor on UI.Methods:A baseline survey with a multistage stratified cluster sampling design was conducted between February 2014 and January 2016, and followed up by telephone from June to December 2018. A total of 55 477 adult women from six provinces of China participated the survey. According to the ratio of 1:1, under sampling method was used to randomly select the same number of women as UI from the non UI women. The data were randomly divided into training set and verification set according to 7:3. The training set was used to establish the random forest model, which including the candidate variables with P<0.2 in univariate analysis, and the verification set was used to verify the predictive effects. Results:A total of 30 658 patients (55.26%, 30 658/55 477) completed the follow-up, the median follow-up time was 3.7 years. Among the 24 985 women without UI at baseline, 1 757 (7.03%, 1 757/24 985) had UI at followed up, including 1 117 (4.47%, 1 117/24 985) with stress UI, 243 (0.97%, 243/24 985) with urgency UI and 397 (1.59%, 397/24 985) with mixed UI. When fixed the number of features as 2 and the number of random trees as 300 in the random forest model, the out of bag error rate estimation was the lowest; with such parameter settings, the classification accuracy was 64.3%, the sensitivity was 64.2%, and the specificity was 64.4%. The top10 predictive UI factors that screening by the variable importance measure in random forest model were obtained as follows: age, parity, delivery pattern, body mass index (BMI), menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.Conclusion:We identified the top10 predictive UI factors that screening by the variable importance in random forest model as follows: age, parity, delivery pattern, BMI, menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.

Effects of programmed cell death protein 4 targeting by microRNA-21-5p on the proliferation and apoptosis of peripheral blood B lymphocytes in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective:To investigate the regulatory effect of miRNA-21-5p on peripheral blood B lymphocyte proliferation and apoptosis in systemic lupus erythematosus (SLE) patients by targeting program-med cell death protein 4 (PDCD4) .Methods:Thirty patients with SLE diagnosed clinically in our hospital were enrolled. Peripheral blood lymphocyte (PBL) was extracted by gradient centrifugation, and B cells were separated by magnetic beads. The proportion of B lymphocyte in peripheral blood was detected by flow cytometry. The cells were divided into five groups by electrotransfection: blank control group, miRNA-21-5p negative control (NC) group, miRNA-21-5p group and miRNA-21-5p inhibitor group, PDCD4 negative control group and PDCD4 siRNA group. Cells were collected 48 hours after transfection. The expression levels of miRNA-21 and PDCD4 were detected by real-time polymerase chain reaction (RT-PCR). Western blotting assay was used to detect the expression of PDCD4 in cells of each group. The targeting relationship between miRNA-21-5p and PDCD4 was verified by double luciferase target experiment. Flow cytometry was used to detect the apoptosis of cells in each group, and CCK-8 method was used to detect the proliferation of cells in each group. Western blotting and RT-PCR were used to detect the expression levels of Fas, FasL, CD40 and CD40L, respectively. Independent sample t test was used to compare the data between the two groups; single factor analysis of variance was used to analyze the results of multiple samples; chi square test was used to compare the positive rate of anti dsDNA antibody. Results:The levels of serum complement [C3 (0.85±0.11) g/L and C4 (0.54±0.09) g/L] in patients with SLE were lower ( t=7.524, P<0.05; t=38.471, P<0.05) than [C3 (1.16±0.17) g/L and C4 (1.57±0.09) g/L] in healthy controls. The levels of anti-dsDNA antibodies (47%), IgG(15.46±0.75) g/L, and IgA (2.68±0.20) g/L were increased than the levels of anti-dsDNA antibodies (17%), IgG (11.95±0.80) g/L, and IgA (2.16±0.11) g/L in healthy controls ( χ2=4.427, P<0.05; t=15.218, P<0.05; t=10.125, P<0.05). The proportion of B lymphocyte [(6.78±0.29)%] and the expression levels of miRNA21-5p (7.52±0.59) in peripheral blood of SLE patients was significantly higher than the proportion of B lymphocyte [(2.03±0.24)%] and the expression levels of miRNA21-5p (3.60±0.62) in healthy controls ( t=59.064, P<0.05; t=19.317, P<0.05), while the expression levels of PDCD4 gene (1.54±0.35) in peripheral blood of SLE patients was significantly lower than that (4.42±0.42) in healthy controls ( t=19.126, P<0.05). Compared with the blank control group and the miRNA-21-5p NC group, cell proliferation in the miRNA-21-5p Inhibitor group was inhibited, and the proportion of apoptotic cells increased ( F=5.244, P<0.05; F=37.903, P<0.05). Compared with the blank control group and PDCD4 NC group, cell proliferation in PDCD4 siRNA group was significantly enhanced, and apoptotic rate decreased ( F=5.956, P<0.05; F=25.431, P<0.05). The results of double luciferase reporter gene assay showed that PDCD4 is the target gene of miRNA-21-5p. Conclusion:miRNA-21-5p may promote the proliferation of peripheral blood B lymphocyte in SLE patients by inhibiting the expression of PDCD4, leading to abnormal lymphocyte apoptosis. miRNA-21-5p can be used as a new target gene for the treatment of systemic lupus erythematosus.

Expression and clinical significance of serum miR-202-3p in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To study the value of miR-202-3p detection in the diagnosis and treatment of systemic lupus erythematosus (SLE) patients.Methods Two hundred and fifty cases of SLE and 100 cases of healthy controls from January 2017 to December 2018 were involved in the study.The expression of serum miR-202-3p in the 2 groups was detected by real-time quantitative polymerase chain reaction method,and its association with the clinicopathological features was analyzed.Statistical analyses were performed using t/Z-test,one-way analysis of variance,Pearson correlation,and receiver operating characteristic (ROC) curve.Results Compared with that in the control group (26.30±0.43),RA group (25.59±0.38)],the expression level of serum miR-202-3p in the SLE group (9.84±0.46) was significantly decreased (F=320.5,P＜0.01).The expression was lower in patients with active SLE (2.10±0.140) than that in those with stable SLE(14.67±0.39) and the difference was statistically significant (t =24.864,P＜0.01).The expression of miR-202-3p was negatively correlated with disease activity in systemic lupus erythematosus (SLEDAI) (r=-0.809 3,P＜0.01).The expression of miR-202-3p in patients with lupus nephritis combined with SLE (0.74±0.06) was significantly lower than that in patients without nephritis (2.81 ±0.15) and the difference was statistically significant (t=9.991,P＜0.01).The area under the ROC curve of serum miR-202-3p as a diagnosis of SLE was 0.974 [95％CI(0.955,0.988),P＜0.01],and its sensitivity and specificity was 90％ and 96.4％,respectively.Conclusion Serum miR-202-3p is highly expressed in SLE patients and is related to disease activity and renal injury in SLE patients.miR-202-3p may be used for SLE diagnosis.

Key anatomies of DeLancey's three levels of vaginal support theory: an observation in laparoscopic surgery / 浙江大学学报·医学版

OBJECTIVE@#To observe and verify the key anatomies of DeLancey's three levels of vaginal support theory through laparoscopic surgery by space dissection technique.@*METHODS@#The features and stress performance of related anatomies were observed and analyzed in laparoscopic type C hysterectomy and pelvic lymphadenectomy for cervical cancer by natural space exposures.@*RESULTS@#The main ligament-like structure at level Ⅰ was the uterosacral ligament, which acted as the main apical fixation in the sacral direction, while the cardinal ligament was mainly composed of vascular system, lymph-vessels and loose connective tissue around them, lacking the tough connective tissue structures, which was connected to the internal iliac vascular system. There were no strong ligaments connected to the tendinous arch of pelvic fascia (ATFP) at the lateral side of vaginal wall at level Ⅱ. ATFP was the edge of the superior fascia of pelvic diaphragm, which was bounded by the fascia of the obturator. Its surface was smooth and close to the levator ani muscle and fuses with the vaginal fascia in about one thirds of middle lower segments of the vagina. When the ureter tunnel is separated, dense connective structures can be found in both anterior and posterior walls near the intersection of the ureter across uterine artery, fixing the bilateral angle of the bladder triangle, starting from the cervix and vagina and ending in the tunica muscularis vesicae urinariae.@*CONCLUSIONS@#Based on the laparoscopic anatomy, the pelvic floor fascia ligament support above the levator ani muscle can be considered mainly around the vagina, and fascial ligament above the levator ani muscle can be simply considered as two parallel planes forming a "double hammock" structure, which may provide more anatomic data for pelvic floor reconstruction.

The influence of different modes of transport on emergency intervention time in patients with ST segment elevation myocardial infarction / 中华急诊医学杂志

Objective To study the time extended for getting emergency intervention in different modes of transportation and factors influencing the modes of transportation of patients with ST elevation myocardial infarction (STEMI).Methods A total of 564 consecutive patients with STEMI admitted from September 2013 to June 2016 were enrolled in the study.The clinical data about time consumed for getting emergency intervention and modes of transportation were collected.Results According to the mode of transportation,patients were divided into three groups:emergency care system (EMS) transportation group (n =96),self-transportation group (n =206) and referral group in which the patients were sent in from other hospitals (n =262).EMS transportation group had significantly shorter total ischemic time before emergency treatment than self-transportation group (229 rin vs.418 min,P ＜ 0.05) and referral group (229 min vs.512 rin,P ＜ 0.05),and significantly shorter length of pre-hospital time than self-arrival group (55 min vs.110 min;P＜0.05) and referral group (55 min vs.372 min;P＜0,05).The referral group had longer pre-hospital time and the self-transportation group had longer door-to-balloon time,but there was no difference in total ischemic time between the self-arrival and referral group (Z =-1.882,P =0.068).Multivariate logistic regression was used to analyze influence factors in mode of transportation:(1) patients characterized with high school or university education,profession of civil service,and their transportation distance more than 30 km were greater in number than referral group (P ＜ 0.05);(2) patients identified with senior middle school education,staff member of public sectors or company,their transportation distance less than 30 km,and with killip grade above Ⅱ were more likely to have EMS transport (P ＜ 0.05);(3) patients defined as businessmen without taking out new rural cooperative medical insurance,taking up transportation distance less than 80 km,and subjecting to killip grade Ⅰ had a higher proportion of individuals of this kind taking self-transportation (P ＜ 0.05).Conclusion Mode of transportation is an important factor that affects the time extended to get emergency intervention.Education level,occupation,medical insurance type,transportation distance,killip grade are associated with modes of transport.

Effect of tripterine on hydrochloric acid-induced acute lung injury in mice / 中华麻醉学杂志

Objective To evaluate the effect of tripterine on hydrochloric acid-induced acute lung injury(ALI)in mice.Methods Eighteen pathogen-free healthy adult male ICR mice,aged 7-9 weeks,weighing 25-30 g,were divided into 3 groups(n=6 each)using a random number table:control group(group C),hydrochloric acid-induced ALI group(group ALI)and tripterine group(group T).ALI was induced by a single intratracheal instillation of hydrochloric acid 2 ml/kg(pH 1.5)via a 24-gauge angiocatheter inserted into the trachea in pentobarbital sodium-anesthetized mice.Tripterine 3 mg/kg was injected intraperitoneally once a day for 3 consecutive days,and then the model was established in group T.The mice were sacrificed at 6 h after instillation,and lung specimens were obtained for microscopic examination and for determination of the levels of tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),macrophage migration inhibitory factor(MIF)and myeloperoxidase(MPO)in lung tissues.Results Compared with group C,the levels of TNF-α,IL-6,MIF and MPO were significantly increased at 6 h after instillation in ALI and T groups(P<0.01).Compared with group ALI,the levels of TNF-α,IL-6,MIF and MPO were significantly decreased at 6 h after instillation in group T(P<0.01).The pathological changes of lung tissues were significantly attenuated in group T compared with group ALI.Conclusion Tripterine can attenuate hydrochloric acid-induced ALI in mice.

FEA technology applied in the design of CT table / 中国医疗器械杂志

In this paper, we develop a method to build FEA model, boundary conditions and to analyse static strength and rigidity of the object based on the CT patient table. Especially to introduce the examples of how to simplify the actual models to ideal models which can easily add some loads. In the end of the paper, we compare the results analysis of FEA with the results of experiment and we confirm the high accuracy of FEA, so we summarize that FEA technology is very important for the development of medical equipment.

Analysis of endoscopic and pathological features of 66 cases with rectum neuroendocrine neoplasm / 中华消化杂志

Objective To analyze the endoscopic and pathological characteristics of rectum neuroendocrine neoplasm (NEN).Methods From January 2005 to May 2012,the endoscopic and pathological data of 66 patients with rectum NEN were collected and graded according to historistic grade of gastroenteropancreatic-neuroendocrine neoplasm (GEP-NEN) by World Health Organization (WHO).The factors related with the metastasis of neuroendocrine tumor (NET) and neuroendocrine cancer (NEC) were analyzed by Chi square test and Fisher exact probability method.Results The locations of 66 NEN cases were between three and 15 cm from the anus.The diameters of 54 cases were less than 1 cm and under endoscopy the appearance of most tumors was submucosal hemispherical polypoid bulge.The diameters of nine cases were over 1 cm but less than 2 cm,of which the appearance of five cases was submucosal thickening or sessile polypoid bulge.The diameter of three cases was over 2 cm and the appearance was cauliflower-like or polypoid tumor which caused annular lumen stenosis.Sixty-one cases were NET (grade G1),three cases were NEC (grade G3) and two cases were mixed adenoendocrine carcinoma with both NEC and adenocarcinoma components.The metastasis of NET and NEC was not related with gender (x2 =0.158,P＞0.05) and age (Fisher exact probability method,P＞ 0.05),however was related with the diameter of tumor (Fisher exact probability method,P＜0.05).Conclusions NEN is a tumor with variety endoscopic characteristics and pathological features.The metastasis of NET and NEC seems not related with gender and age,but related with diameter.

A study of seroconversion of HBsAg in chronic hepatitis B patients with HBeAg positive by combination treatment with interferon and nucleoside analogue / 中华传染病杂志

Objective To study clinical features and mechanism in patients suffered from chronic hepatitis B achieving seroconversion of HBsAg by combination treatment with interferon (IFN) and nucleoside analogue (NA). Methods Thirty-two cases with chronic HBV hepatitis were enrolled into this retrospective study. All of them received combination treatment with IFN and Lamivudine/Adefovir, as well as achieved seroconversion of HBsAg from June, 2001 to May, 2007. All the cases in this study were followed up. Results Generally, serum HBV DNA fell below the detection limit 3 to 6 months after starting combination treatment. Virological breakthrough/relapse or new clinical resistant had not been found in all enrolments after combination treatment, including patients with previous resistant to Lamivudine, although the average length of treatment was over 2 years. The average period of following up after seroconversion of HBsAg was 13.2 months. Two cases transfered back to HBsAg positive, one of them achieved seroconversion of HBsAg again by the anti-virus treatment, and the other one gave up treatment and remained anti-HBe positive and HBeAg negative.The other 30 eases kept at the stage of seroconversion of HBsAg. Seven patients underwent liver biopsy after seroconversion of HBsAg, and 3 of them had taken liver biopsy before combination therapy too. Biopsy specimens were scored for fibrosis and neeroinflammation according to the Knodell histological activity index. Six cases showed HBsAg and HBcAg negative by immunohistochemistry,and only 1 case with HBsAg positive in liver tissue experienced relapse. Inflammation and fibrosis grade of the 3 cases who had taken liver biopsy twice were lowered after HBsAg seroconversion,although the ALT level of 1 case who had turned from G2S4 to GIS2-3 remained abnormal after HBsAg seroconversion. According to the sequence and character of HBsAg seroconversion, there were three models of HBsAg conversion. The sequence of transition was HBV DNA→HBeAg→HBsAg,which was dominant one, accounting for 59%(19/32 cases). HBV DNA negative, and the titer of HBeAg wandering at a low level, after then HBeAg and HBsAg change to negative in the same time,31% (10/32 cases). The titer of HBsAg decreased rapidly after the HBV DNA clearance, and the HBsAg clearance was earlier than HBeAg, 9% (3/32 cases). After 1 year of combination therapy,there were 15 of 21 cases (71.4%) whose titer HBsAg showed less than 100 COI by agent from Roche, and 7 of 11 cases (63.6%) whose titer HBsAg showed less than 250 IU/L by agent from Abbott. The frequency of adverse reaction was similar with that induced by IFN monotherapy, and no new adverse reaction was found. Conclusions Combination therapy and long course treatment might be the key to achieve the HBsAg seroconversion. Those with HBsAg in liver tissue and (or) low serum anti-HBs are more likely to relapse. The titer of HbsAg<100 COI (Roche, Germany) or<250 IU/L (Abbott, USA) after one year treatment may be regarded as a predict index of HBsAg seroconversion.