N6-methyladenosine(m6A)is produced by methylation of the 6th nitrogen atom of ade-nine.The m6A methylation modification is the most common internal modification of RNA,and the modifica-tion process mainly relies on m6A-related enzymes,including methyltransferases,demethylases and binding proteins.The core structure of the methyltransferase complex(MTC)is methyltransferase-like 3(METTL3).The pathogenesis of osteoarthritis(OA)is intricate and complex,and various factors interact with each other.This paper summarizes the mechanism of action of m6A and related enzymes,and elaborates the pathogenesis of os-teoarthritis from the aspects of chondrocytes,proteases,cytokines and signaling pathways,emphatically intro-duces the regulatory role of METTL3 on OA in m6A methylated modification.The aim is to provide new per-spectives on the pathogenesis of osteoarthritis in order to provide new ideas and approaches for the treatment of osteoarthritis.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. The high incidence rate, drug resistance rate and mortality rate of TB infection cause serious social and economic burden in developing countries. Due to high occupational exposure, medical institutions and healthcare workers take the potential risk of TB infection, which have negative impact on the public health and occupational health. As one of the countries with high burden of TB in the world, the occupational exposure of healthcare workers in China is serious, and the infection rate is far higher than that of developed countries. This article reviews the prevalence of latent tuberculosis infection among health care workers and the status quo of occupational protection in medical institutions in China.

Objective:To investigate the effects of poly (ADP-ribose) polymerase-1(PARP-1) in intestinal mucosal barrier injury in rat model with severe acute pancreatitis (SAP).Methods:Twenty healthy male Wistar rats were divided into four groups ( n=5 each group) using a random table method: control, SAP, 3-aminobenzamide (3-AB), and 3-AB control groups. The SAP model was induced by intraperitoneal injection of cerulean with lipopolysaccharide. At 30 min, the rats were treated with the PARP-1 inhibitor, 3-AB, or normal saline,separately. After 12 h, all rats were sacrificed to harvest pancreas tissues, intestines tissues, and blood from the hearts for index detection. Serum amylase (AMY) and interleukin (IL)-6 levels were measured using an automatic biochemical instrument and enzyme-linked immunosorbent assay (ELISA), respectively.The protein expression of PARP-1 and nuclear factor (NF-κB) were measured using Western blot and that of occludin was measured using an immunohistochemical test. One-way analysis of variance was used for comparison of multiple groups of variables. Non-parametric tests of rank conversion were used when variances were not uniform. A P <0.05 was considered statistically significant. Results:Compared to the control group, the following indexes in the SAP group were significantly increased: ascites (with serious hemorrhage and necrosis in the pancreas and disordered intestinal villi),serum AMY and IL-6 levels, and the expression of PARP-1 and NF-κB. However, Occludin expression was significantly decreased. There was no significant difference between 3-AB group and 3-AB control group. Compared to the SAP group, the severity of SAP and pancreatitis-associated intestinal injury was significantly attenuated with the administration of 3-AB. Serum AMY and IL-6 levels were significantly decreased (serum AMY: 1 879.25 ± 736.6 U/L vs 5 569.33 ± 1993.48 U/L; IL-6: 77.98 ± 20.65 pg/mL vs 209.14 ± 79.08 pg/mL, both P<0.05), but the expression of PARP-1 and NF-κB were significantly increased (PARP-1: 1.44 ± 0.09 vs 1.49 ± 0.13; NF-κB: 0.63 ± 0.09 vs 0.96±0.08, both P<0.05). Similarly, Occludin expression was significantly decreased (6.7±1.5 vs 3.2±1.1, P<0.05). Conclusions:Inhibition of PARP-1 has protective effects on SAP associated intestinal mucosal barrier damage. The mechanism may be related to the inhibition of NF-κB signaling pathway and increase intestinal mucosal Occludin protein expression.

Objective: To survey on the home blood pressure measurement and blood pressure control rate among patients with hypertension in Beijing Yuetan community. Methods: A questionnaire survey was conducted among 504 hypertensive patients, who were visiting Beijing Yuetan Community Health Service Center and selected by convenience-sampling method during June 2018 to January 2019. The status of home blood pressure measurement, the awareness of hypertension, the blood pressure control rate and factors related to not regularly measuring were surveyed. Results: Of the 504 patients, 93.7% (472/504) took regular medication, but only 61.5% (310/504) had regular blood pressure measurements; 92.5% (466/504) had sphygmomanometers at home with electronic type mainly; 89.9% (453/504) patients knew the method of blood pressure measurement, but only 11.5% (52/453) had their sphygmomanometer calibrated. Among those who measured blood pressure, 77.4% (240/310) measured per week. The main reason for not measuring blood pressure regularly was that there was no need to measure blood pressure without any discomfort, accounting for 50.0% (97/194). The office blood pressure control rate (with desktop mercury sphygmomanometer) was 62.3% (314/504); the blood pressure control rate both in the morning and at bed time was 61.3% (73/119), that in the morning was 68.1% (81/119) and at bed time was 75.6% (90/119). The control rates of systolic blood pressure and heart rate by home measurement at morning and bedtime were significantly higher than those by office measurement (χ²=5.02, 9.97, 15.51, 13.72; all P<0.05). Conclusions The home blood pressure monitoring rate and knowledge level of hypertension among patients with hypertension in Yuetan community are relatively low. There are some differences in blood pressure control rate between office measurement and home measurement. Comprehensive evaluation is needed in the management process, and the treatment plan should be adjusted according to the specific condition of patients.

Background: MicroRNAs (miRNAs) are key regulators during tumor initiation and progression. MicroRNA-375 (MiR-375) has been proven to play a tumor-suppressive role in various types of human malignancies; however, its biological role in clear cell renal cell carcinoma (ccRCC) remains unclear. The purpose of this study was to explore the biologic role as well as the underlying mechanism of miR-375 in ccRCC progression. Methods: Quantitative polymerase chain reaction (qPCR) was applied to test the expression of miR-375 in tissues and cell lines by t-test. Functional experiments were used to investigate the biological role of miR-375 utilizing a gain-of-function strategy. The target of miR-375 was investigated by bioinformatic analysis and further verified by luciferase reporter assay, qPCR, Western blotting, and functional experiments in vitro. Results: Our study demonstrated that miR-375 was significantly downregulated in ccRCC tissues (cancer vs. normal, 0.804 ± 0.079 vs. 1.784 ± 0.200, t = 5.531 P < 0.0001) and cell lines, and loss of miR-375 expression significantly associated with advanced Fuhrman nuclear grades (Grade III and IV vs. Grade I and II, 1.000 ± 0.099 vs. 1.731 ± 0.189, t = 3.262 P = 0.003). Functional studies demonstrated that miR-375 suppressed ccRCC cell proliferation, migration, and invasion (all P < 0.05 in both 786-O and A498 cell lines). Multiple miRNA target prediction algorithms indicated the well-studied oncogene YWHAZ as a direct target of miR-375, which was further confirmed by the luciferase reporter assay, qPCR, and Western blotting. Moreover, restoration of YWHAZ could rescue the antiproliferation effect of miR-375. Conclusions The data provide the solid evidence that miR-375 plays a tumor-suppressive role in ccRCC progression, partially through regulating YWHAZ. This study expands the antitumor profile of miR-375, and supports its role as a potential therapeutic target in ccRCC treatment.
14-3-3 Proteins ; metabolism ; Carcinoma, Renal Cell ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms ; pathology ; MicroRNAs ; physiology ; Phenotype

Purpose To observe the shape of postnatal early female pelvic diaphragmatic hiatus and the mobility of lower urinary tract bladder neck with three-dimensional transperineal ultrasound,and to analyze the related parameters of postnatal early stress urinary incontinence (SUI) to screen SUI early after delivery and provide objective indices for pelvic floor rehabilitation.Materials and Methods 170 primiparae,including 13 cases of SUI group and 157 cases of asymptomatic group,were operated pelvic floor ultrasonic examination,human pelvic floor midsagittal sections and pelvic diaphragmatic hiatus rebuilding images were obtained,and such related biological parameters as bladder neck mobility and pelvic diaphragmatic hiatus indicators were determined.Results The incidence of SUI at 6-8 weeks after delivery was 4.55％,and that after vaginal delivery was 9.61％,the difference was not statistically significant (P＞0.05).The lower migration of the bladder neck (1.83±0.54) cm on Valsalva maneuver,and transverse diameter (421±0.73) cm,vertical diameter (5.89±0.97) cm and area (20.38±6.30) cm2 of pelvic diaphragmatic hiatus in SUI group were greater than those in the asymptomatic group (P＜0.05),and the difference between parameters of the two groups in resting state and anal shrinkage was of no statistical significance (P＞0.05).Conclusion The shape of urethra,lower migration of bladder neck and the parameters of pelvic diaphragmatic hiatus on Valsalva maneuver are sensitive indicators in ultrasonic evaluation of SUI,are conductive to screening of SUI after early delivery in combination with patient symptoms and can guide the high risk puerpera for early pelvic floor rehabilitation.

ObjectiveTo evaluate the clinical curative effect and security by performing the clinical study ofYinggencao formula in treatment of psoriasis vulgaris with blood-heat TCM syndrome.MethodsA total of 75 patients, diagnosed with Psoriasis Vulgaris Blood-heat RCM syndrome, were randomizedly divided into the treatmeat group with 39 patients and the control group with 36. The treatment group tookYinggencao formula twice daily, while the control group tookQingdai capsules three times daily. All the patients were treated 12 weeks. PASI scores were used as the main outcome and to estimate the curative effect rates.ResultsThe PASI scores of patients in the treatment group (6.97 ± 2.02vs. 16.88 ± 2.91;t=14.380,P=0.009) and the control group (13.14 ± 3.18vs. 17.49 ± 2.32;t=7.780,P=0.013) after treatment showed significantly lower than the scores before. The PASI scores showed significant difference between the two groups after the treatment (P=0.027). The total effective rate of treatment group was significantly higher than the control group (76.9%vs. 61.1%;χ2=5.120, P<0.05).Conclusions TheYinggencao formula therapy showed better effect thanQingdai capsules therapy in treatment of psoriasis vulgaris with blood-heat TCM syndrome.

Objective To explore the authentic perioperative psychological experience of patients undergoing Da Vinci robotic surgery and provide the evidence for effective clinical nursing intervention plans. Methods A total of 12 patients undergoing Da Vinci Robotic surgery were selected and analyzed for the authentic psychological experience by using Colaizzi phenomenological approaches of qualitative research. Results After reorganization, analysis, distilling, five themes were acquired about real psychological experience of Da Vinci robotic surgery, including majority patients gradually psychologically accepting Da Vinci robotic surgeries, the close attention paid by hospital and the professional surgeon alleviateing patients'anxiety, majority patients requiring robotic surgery-associated knowledge and guidance of postoperative rehabilitation, the patients'satisfaction of curative effects about Da Vinci robotic surgery, majority patients with the potential concerns or worries about the expense of medical insurance. Conclusions The patients have potential concerns about new technology, Da Vinci robotic surgery. Thus, during the perioperative period, doctors and nurses should inform patients of the detailed procedures and the advantages of Robotic surgeries, patiently reply to the inquiries from patients, catch the psychological changes of the patients timely with providing the appropriate health guidance, and eventually reinforce their confidence on the new technology.

Objective To evaluate the effectiveness and safety of leuprolide acetate in the treatment of endometriosis. Methods From Nov. 2007 to Oct. 2012, the patients who confirmed to be endometriosis were randomly divided into test group of 113 cases and control group of 116 cases. The test drug was the sustained-release agent of leuprolide acetate. The control drug was Enantone. The drugs were used for 3 times in total. After treatment, the ovarian mass volumes measured with type-B ultrasound, the scores of the patient′s subjective symptoms during non-menstrual and menstruation days, the pelvic signs during non-menstrual days, the changes of hormones [estradiol (E2), FSH, LH], and adverse events were observed. Results After the treatment, the rate of changes of ovarian mass volume (among them, at 12 weeks after the first injection, the median was -55.83% in the test group, -68.22% in the control group, P=0.336), the distinct improvement rate of symptom scores and pelvic signs during non-menstrual days [among them, at 12 weeks after the first injection, the rate of lower abdomen pain was 47.5%(48/101) in the test group, 44.0%(44/100) in the control group, P=0.881], the hormone (E2, FSH, LH) levels [among them, at 12 weeks after the first injection, the serum level of E2, was (33±38) pmol/L in the test group, (38± 40) pmol/L in the control group, P=0.414;the serum level of FSH, was (5.1±2.8) U/L in the test group, (5.3± 2.3) U/L in the control group, P=0.666;the serum level of LH, was (0.6±0.8) U/L in the test group, (0.6±0.9) U/L in the control group, P=0.907], had no statistically significant difference between the two groups (all P>0.05). The distinct improvement rate and improvement rate of symptom (lower abdomen pain, low back pain) scores during menstruation days at 12 weeks after the first injection, the rates of lower abdomen pain were 73.9%(34/46), 15.2%(7/46) respectively in the test group, 72.3%(34/47), 2.1%(1/47) respectively in the control group, had statistically significant difference between the two groups (P=0.026). There was no serious adverse event occurred in both two groups. The incidence rate of adverse event was 33.6%(38/113) in test group, 23.2% (27/116) in control group, there was no significant difference between the two groups (P=0.082). Conclusion Leuprolide acetate is effective and safe in the treatment of endometriosis.