Objective To evaluate the efficacy and safety of immunosuppressive strategy of leflunomide (LEF) combined with calcineurin inhibitor and prednisone in Chinese renal transplant recipients.Methods Prospective clinical study was performed in 16 stable renal transplant recipients treated with calcineurin inhibitor, prednisone and either mycophenolate mofetil (MMF) or azathioprine (Aza), and MMF or Aza was replaced by LEF afterward. The loading dose of LEF was 50 mg/day for 3-5 days, and the maintenance dose was 20 mg/day. Prednisone was maintained 10 mg/day. The doses of CsA were adjusted according to its blood concentration.Results One patient dropped due to economic reason 1 mouth later, and continued to take Aza. Another one patient switched back to MMF due to a slight increase of serum creatinine (from 130 ?mol/L to 143 ?mol/L) 6 months after conversion. The remaining 14 patients were still on LEF. The mean observation time under LEF was (8.7?7.2) months (1～18 month). The mean serum creatinine was (103?24) ?mol/L before conversion, (95?26) ?mol/L at 6th month, and (108?27) ?mol/L at one year post-conversion. There was one episode of biopsy proved reversible acute rejection. The observed side effect was tolerable alopecia in 2 cases and rash in 1 case, but there were no significant increases in liver function, decrease of blood WBC count, deterioration of anemia, or any serious infection in any of the patients.Conclusion Immunosuppressive strategy of LEF+calcineurin inhibitor and prednisone is effective and safe in stable Chinese renal transplant recipients.

The report described one case of vascular paralysis syndrome during kidney transplantation to provide references for clinical practice.After intraoperative opening of kidney artery and vein, the recipient developed vascular paralysis syndrome.However, the efficacy is not obvious after dosing of norepinephrine.After an intravenous infusion of methylene blue, the recipient has a successful removal of tracheal intubation and recovered well.

Objective: To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients. Methods: An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups. Results: Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred. Conclusion DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.

Objective: To investigate the clinical effect of diced cartilage in correcting nasal alar base depression after cleft lip surgery. Methods: A retrospective study was conducted in 15 patients of nasal deformity after lip surgery from January 2018 to January 2019. All the patients were taken from autologous costal cartilage to reconstruct the outline of nasal malformation, and the remaining autologous costal cartilage was cut into 0.5-1.0 mm pieces and filled into the basilar lacunar space of the nasal alar by the 1 ml syringe whose anterior needle nipples was removed. The effects of visual images before and after operation were compared and analyzed by Adobe Photoshop CS6 software. The patients were followed up for 6-15 months (mean 10months). The satisfaction and complications of the patients were investigated. Results: The nasal alar base was significantly elevated and the outline of the nasal deformity was improved in 15 patients after operation. The overall effect was satisfactory and no obvious complications were found. No obvious absorption was found in the follow-up. Conclusions The application of diced cartilage to correct the nasal alar base depression after cleft lip surgery was a feasible method with important clinical value. It advanced in taking good use of the remaining cartilage and reducing the damage to both the donor and recipient area.

AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.

Objective:To investigate the prognostic factors of Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG) after radical resection with different surgical approaches.Methods:The retrospective case-control study was conducted. The clinicopathological data of 442 patients who were admitted to Tianjin Medical University Cancer Institute and Hospital from February 2003 to July 2011 were collected. There were 362 males and 80 females, aged from 21 to 85 years, with a median age of 64 years. Patients underwent radical resection of AEG. Observation indicators: (1) surgical situations; (2) follow-up; (3) progrostic factors analysis of AEG after radical resection; (4) survival of patients after radical resection of AEG via abdominal approach; (5) survival of patients after radical resection of AEG via thoracoabdominal approach; (6) survival of patients after radical resection of Siewert type Ⅱ type AEG; (7) survival of patients after radical resection of Siewert type Ⅲ AEG. Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to June 2018. Measurement data with skewed distribution were described as M (range). Count data were expressed as absolute numbers or percentages. Kaplan-Meier method was used to calculate survival rates and draw survival curves, and Log-rank test was used for survival analysis. Univariate analysis was conducted using the Kaplan-Meier method. Multivariate analysis was conducted using the COX proportional hazard model. Results:(1) Surgical situations: 442 patients underwent radical resection of AEG, including 204 via abdominal approach and 238 via thoracoabdominal approach. There were 391 patients with D 2 lymphadenectomy and 51 with D 2+ lymphadenectomy. (2) Follow-up: 442 patients were followed up for 8-162 months, with a median follow-up time of 37 months. All the 442 patients survived for 2-156 months, with a median survival time of 31 months. The 1-, 3-, 5-year overall survival rates were 79.2%, 42.0%, 30.0%, respectively. (3) Prognostic factors analysis of AEG after radical resection: results of univariate analysis showed that tumor diameter, Lauren type, pathological T staging, pathological N staging, pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were related factors for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( χ2=4.028, 4.885, 19.435, 17.014, 34.449, 9.707, 11.866, P<0.05). Results of multivariate analysis showed that pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration were independent influencing fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG ( hazard ratio=1.255, 0.486, 1.454, 95% confidence interval: 1.024-1.539, 0.325-0.728, 1.096-1.928, P<0.05). (4) Survival of patients after radical resection of AEG via abdominal approach: of the 204 patients undergoing radical resection of AEG via abdominal approach, the 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients with Siewert type Ⅱ AEG, respectively, versus 72.0%, 39.3%, 31.8% for 83 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=1.854, P>0.05). (5) Survival of patients after radical resection of AEG via thoracoabdominal approach: of the 238 patients undergoing radical resection of AEG via thoracoabdominal approach, the 1-, 3-, 5-year survival rates were 79.6%, 38.8%, 23.8% for 183 patients with Siewert type Ⅱ AEG, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients with Siewert type Ⅲ AEG, showing no significant difference in the survival between the two groups ( χ2=0.215, P>0.05). (6) Survival of patients after radical resection of Siewert type Ⅱ AEG: of the 304 patients with Siewert typeⅡAEG, the postoperative 1-, 3-, 5-year survival rates were 83.6%, 50.4%, 37.8% for 121 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.6%, 38.8%, 23.8% for 183 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=2.406, P>0.05). (7) Survival of patients after radical resection of Siewert type Ⅲ AEG: of the 138 patients with Siewert type Ⅲ AEG, the postoperative 1-, 3-, 5-year survival rates were 72.0%, 39.3%, 31.8% for 83 patients undergoing radical resection of AEG via abdominal approach, respectively, versus 79.1%, 37.6%, 29.3% for 55 patients undergoing radical resection of AEG via thoracoabdominal approach, showing no significant difference in the survival between the two groups ( χ2=0.640, P>0.05). Conclusions:Pathological TNM staging, lymphatic vessel invasion, and soft tissue infiltration are independent fators for prognosis of patients after radical resection of Siewert type Ⅱ and Ⅲ AEG. Siewert types and surgical approach are not related factors for prognosis of patients after radical resection of AEG. There is no significant difference in the survival between patients with different Siewert types of AEG undergoing radical resection via different surgical approaches.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

OBJECTIVETo understand the prevalence of informing doctors of the HIV infection status during medical care seeking and influential factors among people living with HIV/AIDS.

METHODSThe study was conducted among people living with HIV/AIDS in 7 provinces in China, including those receiving HIV test, HIV counsel and HIV infection treatment. The data were analyzed with software SAS 9.2. Chi-square test was used to compare the informing rates in patients with different characteristics. Univariate and multivariate logistic regression analyses were conducted to identify the influential factors.

RESULTSOf the 2 432 HIV/AIDS patients, 49.7% (716/1 442) didn't inform the doctors of their HIV infection status actively. The non-active informing rate was 51.9% (559/1 077) in males, 62.9% (212/337) in age group 18-30 years old, 58.1% (555/955) in those with a educational level >primary school, 65.7% (241/367) in those working in private/joint companies or the self employed and 62.5% (197/315) in those living in small cities. The non active informing rate was highest in those infected through sexual contact (66.3%, 275/415). Multivariate logical regression analysis indicated that those infected through illegal blood donation would like to inform of the HIV infection status actively (OR=0.083, 95% CI: 0.049-0.141) , but those working in private/joint companies or the self employed would like not to inform of the HIV infection status actively (OR=1.531, 95% CI: 1.017-2.304).

CONCLUSIONThe non active informing rate of HIV infection status was high in people living with HIV/AIDS. It is necessary to conduct the targeted health education to encourage people living with HIV/AIDS to inform of their HIV infection status actively.

Acquired Immunodeficiency Syndrome ; Adolescent ; Adult ; China ; Communicable Diseases ; Communication ; Female ; HIV Infections ; Health Behavior ; Health Education ; Humans ; Male ; Mass Screening ; Physician-Patient Relations ; Prevalence ; Sexual Behavior ; Young Adult

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.