Tubulointerstitial renal fibrosis is an essential feature of diabetic nephropathy (DN). Pericytes play a critical role in microvascular diseases and renal fibrogenesis. However, the role of pericytes in DN remains unclear. Herein, we aimed to explore the properties and possible mechanisms of pericytes in renal fibrosis in DN. Methods: We used multiplex immunofluorescence staining to evaluate the location and expression of activated pericytes and to assess capillary dilation and interstitial fibrosis in the kidneys of db/db mice. Pericytes were co-stained for alpha-smooth muscle actin (α-SMA) to determine which ones differentiate into myofibroblasts in db/db mice. Expression of CD34 and platelet-derived growth factor receptor beta (PDGFR-β) was assessed in kidney tissue from patients with DN by immunohistochemical staining. Results: We found that cell staining for nerve/glial antigen 2 (NG2)+ and PDGFR-β+ was greater in the kidneys of db/db mice than in those of db/m mice. There was impaired pericyte coverage of blood vessels and capillary dilation in the renal interstitium. These changes were accompanied by increased collagen I staining and an increase in the number of pericytes with profibrotic phenotypes, as identified by increased NG2+/PDGFR-β+/α-SMA+ and decreased NG2+/PDGFR-β+/α-SMA– staining. In DN patients, expression of PDGFR-β was stronger and there was loss of CD34 compared with the findings in control patients with minor glomerular lesions. Conclusion: In this study, we demonstrated that pericyte activation accompanied by peritubular capillary dysfunction and pericytemyofibroblast transition is associated with renal fibrosis in DN.

Objective To investigate the performance of different methods in common autoantibody detec-tion,and to provide basis for the detection strategy of autoantibody.Methods A total of 2 657 cases were in-cluded in this study,whose serum antinuclear antibody(ANA)by indirect immunofluorescence method(IIF)and antinuclear antibody spectrum(ANAs,a total of 15 antibodies)by immunoblot method(IB)were tested simultaneously,and anti-double strand DNA antibody(anti-dsDNA antibody)were tested by IIF,enzyme linked immunosorbent assay(ELISA)and IB.ANCA and ANCA spectrum[anti-myeloperoxidase antibody(anti-MPO antibody),anti-protease 3 antibody(anti-PR3 antibody)]were tested by IIF and ELISA respec-tively in 2 348 cases.Results Firstly,the detection rate of ANA was significantly higher than that of ANAs(57.77％vs.30.64％,P＜0.001).Among the specimens detected with ANA,40.78％detected at least one specific antibody positive.Among the specimens detected with ANAs positive,ANA was not detected in 23.10％of cases.Secondly,the ANA positive cases were mainly of lower titers,and cases with titer of ≤1∶320 accounted for 84.95％of the total detected cases.But the higher the titer,the higher the detection rate of ANAs specific antibodies(29.63％in 1∶100,48.56％in 1∶320,77.78％in 1∶1 000,92.42％in≥1∶3 200).Thirdly,among the specimens detected ANAs positive,the composition ratios of anti-Scl-70,anti-PM-Scl and anti-PCNA antibodies in ANA positive cases was significantly lower than those in ANA negative cases(P＜0.001).Fourthly,the detection rate of anti-dsDNA antibody by ELISA was the highest(4.14％),which was significantly higher than those by IIF or IB(both P＜0.001),and the difference in detection efficacy of the latter two methods was also statistically significant(P＜0.001).Even so,the IIF and IB for the detection of anti-dsDNA antibody still had a certain complementary effect on ELISA.Fifthly,the positive rate of ANCA by IIF was significantly higher than that of ANCA spectrum(9.16％vs.2.43％),but among those who were detected anti-MPO antibodies and/or anti-PR3 antibodies positive,47.37％were ANCA negative.Conclusion Different methods for detecting autoantibodies have significantly different detection efficacy,and it is partic-ularly necessary to adopt correct detection strategies based on evidence-based medicine.

Objective:To investigate the effect of lncRNA SNHG6 on the proliferation and radiotherapy sensitivity of cervical cancer SiHa cells and its potential mechanism.Methods:The expression levels of lncRNA SNHG6 and miR-485-3p in cervical cancer tissues, paracancer tissues, SiHa cells and SiHa cells exposed to X-ray were detected. The relationship between lncRNA SNHG6 and miR-485-3p was analyzed. After overexpression or knockdown of SNHG6 and miR-485-3p, cell proliferation ability, number of invasion and apoptosis rate were determined by MTT, Transwell chamber assay and flow cytometry, respectively. The effect of miR-485-3p on the Wnt/β-catenin pathway and the effect of XAV939 on SiHa cell proliferation and radiation sensitivity were analyzed.Results:lncRNA SNHG6 was highly expressed in cervical cancer tissues and SiHa cells, whereas was lowly expressed in X-ray irradiated SiHa cells. miR-485-3p was lowly expressed in cervical cancer tissues and SiHa cells, whereas was highly expressed in X-ray irradiated SiHa cells. lncRNA SNHG6 targeted miR-485-3p. Down-regulation of lncRNA SNHG6 expression inhibited cell proliferation and invasion, and enhanced its sensitivity to X-ray radiotherapy, while miR-485-3p inhibitor transfected cells exerted the opposite effect. The up-regulation of lncRNA SNHG6 promoted the proliferation and invasion of SiHa cells through miR-485-3p, and reduced the sensitivity of radiotherapy. Down-regulation of miR-485-3p activated the Wnt/β-catenin pathway, promoted cell proliferation and invasion of SiHa, and reduced its radiation sensitivity to X-ray.Conclusion:Overexpression of lncRNA SNHG6 targeting miR-485-3p activates the Wnt/β-catenin pathway to regulate the proliferation and radiotherapy sensitivity of SiHa cells.

Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.

Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.

Objective To analyze the clinical significance of endometrial abnormalities in patients with breast cancer after oral administration of tamoxifen, and to determine the risk factors for endometrial malignancy. Methods We collected data from 135 patients with breast cancer who underwent surgery for endometrial abnormalities after oral administration of tamoxifen at the Department of Gynecology from September 2011 to December 2017. According to the pathological results obtained, the patients were divided into groups A (benign endometrial lesion) and B (precancerous and malignant endometrial lesion). The relationships between endometrial malignancy and factors including age, menopausal status, body mass index, endometrial thickness, abnormal uterine bleeding, oral dose of tamoxifen, duration of oral medication, and complications (hypertension and diabetes) were compared between the groups. Results There were 124 patients in group A and 11 patients in group B. The difference in the incidence of abnormal uterine bleeding, which was a risk factor for endometrial malignancy, was significant different between the groups (P ＜ 0.05). Conclusion Physicians should pay close attention to abnormal uterine bleeding in patients taking tamoxifen after surgery for breast cancer. Hysteroscopy should be used to confirm the nature of lesions, and patients without symptoms should be followed up.

Endometrial cancer is a common malignancy of the female reproductive system. Despite improvement in living standards, the incidence of endometrial cancer is increasing due to the lack of effective screening. Early detection of endometrial cancer and precancerous lesions can significantly improve prognosis and survival. At present, China lacks a method for screening endometrial lesions comparable to that for cervical cancer screening. A recently introduced endometrial sampler has the advantages of simple operation, low cost, and minimal trauma, and is gradually being accepted for clinical screening of endometrial cancer and precancerous lesions in other countries.This study aims to explore current screening methods for endometrial cancer and precancerous lesions and the clinical application of an endometrial sampler for screening.

Tumor-derived exosomes (TEXs) are small membrane vesicles secreted by tumor cells.They contain various proteins and RNA which make they serve as functional mediators in cell interaction.TEXs can alter the components of extracellular matrix and induces epithelial-mesenchymal transition of tumor cells,which enhance the invasiveness of tumor cells.TEXs regulate immunity through multiple pathways,allowing circulating tumor cells to escape immune surveillance.TEXs promote pre-metastatic microenvironment in target organ before metastasis and induce angiogenesis after circulating tumor cells colonization.Understanding the role and mechanism of TEXs in this process can effectively block relevant signaling pathways which may provide new targeted therapies for clinic.

Objective To observe the effect of adenosine A1 receptor (A1AR) on the megalin defect in type 1 diabetic mice with early kidney disease.Methods 7-8 week-old,baseline body weight and fasting blood glucose matched wild type (WT) C57BL/6J mice were selected,and randomly divided into two groups:control group (n=6) and WT DM group (n=6).In the same way,male A1AR knock-out C57BL/6J mice were selected as A1AR-/-DM group (n=6).DM model was established by intraperitoneal injection of streptozocin.The blood glucose (BG),body weight (BW),kidney weight (KW),24 h proteinuria (24hUP) and albumin creatine ratio (ACR) were measured at 4 weeks.The renal pathological lesion was observed and the expression of megalin in proximal tubules was examined by immunohistochemistry.The expression of caspase-1,IL-18 and A1AR were detected by Western blotting.Results At 4th week,compared with WT control mice,the BG,BW,KW and 24hUP of WT DM mice were increased significantly (n=6,P ＜ 0.01),with the pathological glomerular enlargement,mesangial cell proliferation,extracellular matrix accumulation and renal tubule hypertrophy being observed.Immunohistochemistry revealed decreased expression of megalin,an important multiligand protein receptor on the brush border of proximal tubular epithelial cells in WT DM mice,which was correlated with 24hUP (r=-0.645,P ＜ 0.01).Compared with the control mice,the expressions of caspase-1,IL-18 and A1AR were significantly increased in WT DM mice (P ＜ 0.05).For A1AR-/-DM mice,more serious pathological lesion and megalin defect,together with increasing of casapase-1 and heavier proteinuria were observed than those in WT DM mice.Conclusion A1AR may play a protective role in megalin expression of diabetic mice with early kidney disease,in which the mechanism may be associated with caspase-1 related pyroptosis pathway.The details need further exploration.