The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.

Dendritic cells (DCs) as a rare type of leukocytes play an important role in bridging the innate and adaptive immune system. A subset of DCs, monocyte-derived dendritic cells (moDCs), exists in very low numbers at steady state but become abundant in inflammatory states. These inflammation-associated DCs are potent producers of pro-inflammatory cytokines and potent inducers of T helper differentiation. They behave as a "double-edge" sword so that they not only mediate protective immunity but also immuno-pathology. It is still incompletely understood how their function is regulated. Emerging evidence indicates that microRNAs (miRNAs), as a new class of gene regulators, potently regulate the function of moDCs. Here we summarize recent progress in this area.
Animals ; Antigen Presentation ; genetics ; Cell Differentiation ; Cytokines ; genetics ; metabolism ; Dendritic Cells ; metabolism ; physiology ; Humans ; Inflammation ; immunology ; pathology ; MicroRNAs ; metabolism ; physiology ; RNA Interference

Objective To investigate the changes of brain function in moderate and high myopia patients using fractional amplitude of low frequency fluctuation (fALFF),and discuss the correlation between brain function changes and clinical data of patients with myopia.Methods Totally 21 moderate and high myopia patients (myopia group),and 21 healthy volunteers (normal control group) who were matched with myopia patients in age and gender,were selected to take rs-fMRI examination.The difference of fALFF of brain functional activity in patients with myopia and normal controls was compared,and the correlation between the changes of fALFF and clinical data of patients with myopia was analyzed,Results Compared with normal control group,the fALFF values of myopia group in the region of the left inferior frontal gyrus,putamen and right inferior frontal gyrus,putamen and insula were significantly lower (all P ＜ 0.05,AlphaSim corrected).However,in bilateral cingulate gyrus,bilateral anterior cingulate gyrus,left postcentral gyrus,left superior parietal lobule and region,fALFF values were increased (all P ＜ 0.05,AlphaSim corrected).Conclusion Patients with myopia are accompanied by abnormal neuronal activity in many brain areas,which may reflect the dysfunction of language understanding and attention control in myopic patients.

Objective: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients.Methods: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013.The 3 and 5-year can-cer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.Results: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients.The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months.The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively;the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively.The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001).The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009).Conclusion: T2N0M0 UTUC has a better cancer-specific survival.The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier.The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality;the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

Objective To explore the reasons for withdrawal from peritoneal dialysis (PD) in our hospital.Methods This was a single-center,retrospective cohort study.Patients who started PD in the Department of Nephrology,the First Affiliated Hospital of Nanchang University from November 1st,2005 to February 28th,2017,were enrolled,and followed up to May 31,2017.Patients who continued PD after May 31,2017 were as the control group.Patients who withdrew from PD were divided into 4 subgroups:death group,hemodialysis group,kidney transplantation group and loss of follow-up group.The clinical characters of 4 subgroups were compared with the control group.Results A total of 998 patients were enrolled with age of (49.36± 14.94) when PD started and median dialysis duration of 27.13(12.84,42.29) months,in whom 570 patients (57.11％) were male.Five hundred and seventeen dropout events were recorded,and the dropout rate was 51.80％.The main reason for withdrawal from PD was death (258 patients,49.90％),followed by hemodialysis (166patients,32.11％),kidney transplantation (66 patients,12.77％) and loss to follow-up (27 patients,5.22％).The leading cause of death was cardio-cerebro-vascular diseases (136 cases,52.71％),followed by infection (42 cases,16.28％),dyscrasia (20 cases,7.75％) and tumor (5 cases,1.94％).The main reason for transfering to hemodialysis was insufficient dialysis (76 cases,45.78％),followed by peritonitis (55 cases,33.13％) and catheter dysfunction (24 cases,14.46％).Compared with those in the control group,in the death group patients were older at PD commencement,and had higher proportions of hypertension,diabetes and cardio-cerebro-vascular diseases (all P ＜ 0.05).The proportions of male and diabetes mellitus were higher in the hemodialysis group than those in the control group (both P ＜0.05).Biochemical indicators showed that serum albumin and blood phosphorus were lower in the death group than those in the control group (both P ＜ 0.05);blood albumin was significantly lower in the hemodialysis group than that in the control group (P ＜ 0.05).Conclusions The main reasons for withdrawal from PD in our center are death and transfering to hemodialysis.The cardio-cerebro-vascular disease is the leading cause of death,and inadequate dialysis is the main reason for transfering to hemodialysis.

OBJECTIVETo compare the perioperative safety and efficacy between hand-assisted laparoscopic surgery(HALS) and conventional open sigmoidectomy.

METHODSA total of 291 patients with sigmoid colon cancer who underwent surgery in our hospital from January 2010 to June 2013 were seperated into (HALS) group (n=200) and conventional open surgery (COS) group (n=91) with a non-randomized method. The perioperative safety and efficacy of two groups and perioperative outcomes were compared.

RESULTSThese two groups were comparable in operative time, lymph node harvest, and postoperative complications. However, HALS group had less intraoperative bleeding [(57.9±28.3) ml vs. (82.5±47.6) ml, P=0.000], shorter time to flatus [(3.0±1.4) d vs. (3.3±0.9) d, P=0.000], and shorter hospital stay [(7.3±4.2) d vs. (8.9±4.4) d, P=0.004]. There werer no significant differences in overall survival time and disease-free survival time between the two groups during 6 months to 3 years follow-up.

CONCLUSIONSHALS results in similar outcomes of conventional open surgery for sigmoidectomy with the advantage of minimal invasiveness.

Colectomy ; Disease-Free Survival ; Hand-Assisted Laparoscopy ; Humans ; Length of Stay ; Lymph Nodes ; Operative Time ; Postoperative Complications ; Postoperative Period ; Prospective Studies ; Sigmoid Neoplasms ; Treatment Outcome

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC).Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied.There were 69 males and 79 females,aged from 34 to 82 years old (average 68 years old).83 patients were accompanied with hydronephrosis.80 patients were renal pelvic carcinoma.32 patients had the history of smoking.24 patients had the history of ureteroscope.68 patients had the tumor larger than 3 cm.Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions.We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher' s exact test.Cancer specific survival was analyzed using the Kaplan-Meier method,with the log-rank test used to assess significance.A Cox proportional hazard model was used for multivariate analysis.Results Of the 148 patients,non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51 (34.5％) and 119 (80.4％),respectively.High grade (G3) tumors of primary UTUC and bladder recurrence were 41 (27.7％) and 53(35.8％),respectively.During follow-up,94 (63.5％) experienced bladder recurrence once and 54 (36.5％) experienced multiple bladder recurrence.The median follow-up time was 59.5 (rang 8-142) months,48 (32.4％) patients died of UTUC.The grade of bladder cancer recurrence correlated with the grade (P =0.046),muscle-invasion (P =0.002) and tumor architecture (P =0.034) of the primary UTUC;muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P =0.009);bladder multiple recurrence related to gender (P =0.007).On multivariate logistic regression analysis,the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR =5.512,95％ CI 1.654-18.37,P =0.004) and high grade (HR =3.948,95％ CI 1.589-9.813,P =0.004) bladder recurrence tumor.The muscle invasion of primary UTUC (HR =3.498,95％ CI 1.569-7.803,P =0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis.Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor,and the female could be more likely to appear multiple recurrence tumor.The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival.

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′s exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.