Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Comprehensive Laboratory of Biochemistry and Molecular Biology is a compulsory open online course that integrates lab skill training and innovation ability training for undergraduates majoring in biology in Beijing Normal University. This course focuses on alkaline phosphatase, including cloning of the Escherichia coli alkaline phosphatase gene, expression and purification of the protein, research on its enzymatic characteristics, preparation of its antibody and determination the titers of the antibody, etc. The comprehensive lab course covers from the gene to the protein, so that students can learn and master commonly used biochemical and molecular biology experimental techniques systematically. Escherichia coli alkaline phosphatase is an ideal experimental research object. And there are very classic and systematic scientific research literature reports. As important auxiliary teaching means, these literature resources can help teachers and students to carry out learning inquiries, form rational and critical scientific attitudes and spirits, and also greatly improve the quality of teaching and students' scientific research quality, which plays an important role in the construction of first-class course of Comprehensive Laboratory of Biochemistry and Molecular Biology.

Objective:To propose a Chinese diagnostic criterion for rosacea on the basis of clinical feature analysis of rosacea, and to assess its sensitivity and specificity.Methods:A total of 3 350 Chinese patients with newly diagnosed rosacea were collected from Department of Dermatology, Xiangya Hospital, Central South University between December 2017 and July 2018, their phenotypes and clinical features were retrospectively analyzed, and a Chinese modified diagnostic criterion for rosacea was put forward. A national multi-center clinical observational trial, which included 2 269 patients with rosacea and 2 408 patients with other facial skin diseases from 28 centers, was conducted to verify this diagnostic criterion. Then, the sensitivity and specificity of the modified diagnostic criterion were evaluated by comparing with the 2017 standard classification of rosacea developed by the National Rosacea Society Expert Committee (NRSEC) .Results:Fixed centrofacial erythema occurred in 3 350 (100%) patients with rosacea. Flushing occurred before or simultaneously with fixed erythema in 1 850 (99.4%) of the 1 861 patients with erythema on the cheeks; among the 1 489 patients with erythema on the nose or perioral area, only 52 (3.5%) had flushing; all the 342 patients presenting with phymatous changes had fixed erythema before phymatous changes. Based on the above clinical findings, it was proposed that patients with periodically aggravated fixed erythema on the cheeks accompanied with flushing could be diagnosed with rosacea; patients with fixed erythema on the nose and perioral area accompanied with at least one of selective phenotypes (flushing, telangiectasia, papules and pustules, phymatous changes, or ocular manifestations) could be diagnosed with rosacea. The national multi-center clinical observational trial revealed that the sensitivity of the Chinese modified diagnostic criterion for rosacea was 99.6%, which was close to the sensitivity (100%) of the NRSEC standard, and its specificity was 91.9%, higher than the specificity (73.3%) of the NRSEC standard.Conclusion:The Chinese modified diagnostic criterion for rosacea has good sensitivity and specificity, and can facilitate the early diagnosis of phymatous rosacea.

Objective: High PM concentration is the main feature of increasing haze in developing states, but information on its microbial composition remains very limited. This study aimed to determine the composition of microbiota in PM in Guangzhou, a city located in the tropics in China. Methods: In Guangzhou, from March 5 to 10 , 2016, PM was collected in middle volume air samplers for 23 h daily. The 16S rDNA V4 region of the PM sample extracted DNA was investigated using high-throughput sequence. Results: Among the Guangzhou samples, , , , , and were the dominant microbiota accounting for more than 90% of the total microbiota, and was the dominant gram-negative bacteria, accounting for 21.30%-23.57%. We examined the difference in bacterial distribution of PM between Beijing and Guangzhou at the genus level; was found in both studies, but was only detected in Guangzhou. Conclusion In conclusion, the diversity and specificity of microbial components in Guangzhou PM were studied, which may provide a basis for future pathogenicity research in the tropics.
Air Microbiology ; Air Pollutants ; analysis ; Bacteria ; classification ; isolation & purification ; China ; Cities ; Environmental Monitoring ; Microbiota ; Particle Size ; Particulate Matter ; analysis ; RNA, Bacterial ; analysis ; RNA, Ribosomal, 16S ; analysis

Background and Objectives: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. Methods: and Results: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. Conclusions Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

OBJECTIVE: To detect the expression of CRLF2 in bone marrow mononuclear cells from children with newly diagnosed acute lymphoblastic leukemia(ALL) and to explore its clinical significance in pediatric ALL. METHODS: A total of 218 children with newly diagnosed ALL who achieveal the complete remission and had the complete follow-up information were selected, and the expression level of CRLF2 in bone marrow mononuclear cells of these children was detected by real-time fluorescent quantitative PCR, and the significance of CRLF2 expression level in clinical prognosis of ALL children was analyzed by using statistical method. RESULTS: 28 cases in 218 children with complete data showed high expression of CRLF2. The cumulative recurrence rate in the CRLF2 high expression group was significantly higher than that in the low expression group (53.6% vs 12.6%) (P＜0.01). The predicted 5-year recurrence-free survival rate (RFS) of ALL children with CRLF2 high expression was significantly higher than that of low expression group (P＜0.01). There was no significant difference in the predicted 5-year RFS between ALL children with CRLF2 low and high expression in the standard-risk(SR) group (P＞0.05). The predicted 5-year RFS of ALL children with CRLF2 low expression was higher than that of ALL children with CRLF2 high expression in the intermediate-risk (IR) and high-risk (HR) groups. (P＜0.05). Cox analysis showed that CRLF2 high expression is an independent risk factor for the relapse of children with ALL. CONCLUSION The recurrence rate of pediatric ALL with CRLF2 high expression is high, and CRLF2 high expression is an important prognostic factor for high risk of relapse in ALL children with IR and HR. It is necessary to use CRLF2 expression as an indicator of risk stratification in pediatric ALL.
Bone Marrow ; Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Receptors, Cytokine ; metabolism ; Recurrence ; Risk Factors

AIM:To study the effect of Aurora protein kinase inhibitor VX-680 on homogeneous adhesion and migration ability in human hepatocellular carcinoma cell line HepG 2.METHODS:The HepG2 cell were divided into ex-perimental group and control group, respectively.VX-680 was used in experimental groups at 3 concentrations(3.125 μmol/L group,6.25 μmol/L group and 12.5 μmol/L group).DMSO was used in the control group.The effects of VX-680 at different concentrations on the adhesion ability of human hepatocellular carcinoma HepG 2 cells were observed by cell slow aggregation test and separation experiment.The effects of VX-680 at different concentrations on the migration ability of HepG2 cells was detected by wound healing assay.The expression of E-cadherin in HepG2 cells was detected by Western blot.RESULTS:The results of the slow aggregation test showed that compared with the control group,the number of cell clumps formed in experimental groups was significantly decreased(P<0.01).The results of separation experiment showed that the ratio of NTC/NTEgradually decreased with the increased concentration of VX-680.The results of wound healing as-say showed that as the concentration of VX-680 increased, the cell scratch healing ability gradually weakened compared with control group.The results of Western blot showed that the protein expression of E-cadherin in the HepG2 cells in-creased with the increased concentration of VX-680(P<0.05).CONCLUSION:VX-680 increases the homogeneous ad-hesion and inhibits the migration of HepG 2 cells.