Objective:To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB).Methods:144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ2 test between groups. Results:41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline ( OR = 0.090, 95% CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level ( OR = 7.788, 95% CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95% CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two ( Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95% CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification ( Z = 3.017, P = 0.003) and 24-week drop in HBsAg level ( Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks ( HR = 0.364, 95% CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion:The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

Objective:To investigate the relationship between glycemic variability and glycosylated hemoglobin (HbA1c) level during follow-up in elderly male patients with type 2 diabetes.Methods:Retrospective cohort study. A total of 200 elderly male patients who received continuous glucose monitoring from January 2007 to January 2011 were recruited in the Second Medical Center of PLA General Hospital. The subjects were divided into two groups according to baseline mean amplitude of glycaemic excursion (MAGE) level, including MAGE <3.9 mmol/L group ( n=114) and MAGE ≥3.9 mmol/L group ( n=86). The correlation between baseline MAGE and mean HbA1c during follow-up were evaluated by univariate Pearson correlation analysis and multivariate linear regression analysis. Results:Baseline characteristics including age, body mass index, waist circumference, smoking, drinking, fasting blood glucose, blood lipid and blood pressure were comparable between MAGE <3.9 mmol/L group and MAGE ≥3.9 mmol/L group. The average follow-up period was 12.5 years. The mean HbA1c during follow-up in MAGE ≥3.9 mmol/L group was significantly higher than that in MAGE <3.9 mmol/L group (7.23%±0.72% vs. 6.91%±0.77%, t=-2.94, P=0.004). The proportion of mean HbA1c <7.0% during follow-up in MAGE ≥3.9 mmol/L group was 44.2% (38/86), which was significantly lower than that in MAGE <3.9 mmol/L group [60.5% (69/114), χ 2=5.26, P=0.022]. In univariate analysis, MAGE at baseline was correlated with the mean HbA1c during follow-up ( r=0.306, P<0.001). Multivariate linear regression analysis suggested that the baseline MAGE remained an independent influential factor of mean HbA1c ( β=0.09, 95% CI: 0.03 to 0.15, P=0.006, R2=0.31) after several confounding factors were adjusted. Conclusions:With the increased glycemic variability at baseline, mean HbA1c level during follow-up is accordingly elevated. The glycemic variability at baseline is independently related to mean HbA1c level during follow-up in elderly male patients with type 2 diabetes.

Objective To explore the synergism efficacy and mechanism of Warm Purgative and Strengthening Spleen (WPSS) therapy combined with antibiotics in the treatment of sepsis. Methods Thirty-two SPF Spargue-Dawley (SD) rats were used to replicate the rat sepsis model by cecum ligation perforation (CLP) method and equally divided into model control (MC) group, ceftriaxone group, Chinese herbal medicine (CHM) group and ceftriaxone +CHM group. Eight SD rats underwent sham surgery were used as a sham operation (Sham) group. Rats in Sham and MC groups were administered with 0.9% normal saline (NS) by intraperitoneal injection and gavage. Rats in CHM group were administered with modified Dahuang Fuzi Decoction (DFD, 8 mg/kg) by gavage + 0.9% NS by intraperitoneal injection, Bid. Rats in ceftriaxone group were administered with 0.9% NS by gavage and ceftriaxone (120 mg/kg) by intraperitoneal injection, Bid. Rats in ceftriaxone + CHM group were administered with modified DFD (8 mg/kg) by gavage and ceftriaxone (120 mg/kg) intraperitoneal injection, Bid. The drugs were given for 2 days. The mortality of rats in each group was observed after treatment. The intestinal flora changes and intestinal permeability [intestinal mucosa injury index (IMII), intestinal mucosa secretory immunoglobulin (sIgA), serum D-lactic acid, diamine oxidase (DAO) and sIgA] were detected. Meanwhile, the levels of serum inflammation indexes [lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were detected. Results ① Mortality: ceftriaxone+CHM group (25.0%) < CHM group (37.5%) and ceftriaxone group (37.5%) < MC group (50.0%), the differences between groups were statistically significant (all P < 0.05). ② 16S rDNA sequencing analysis: the ratio of Bacteroidetesin in MC group was lower than that in the Sham group [(24.36±7.15)% vs. (45.20±6.05)%], and the ratio of Proteobacteria in MC group was higher than that in Sham group [(10.03±7.55)% vs. (0.41±0.21)%]. The diversity of intestinal flora in ceftriaxone group was significantly lower than that in Sham and CHM groups (404.60±17.09 vs. 470.80±16.97, 469.20±14.59), the differences between groups were statistically significant (all P < 0.05). The principal component analysis (PCA) suggested that the composition of CHM group was closer to that of Sham group, which indicated that WPSS therapy could reduce intestinal flora disorders in rats with sepsis. ③The pathological changes of intestinal mucosa: light microscope showed the intestinal mucosa of Sham group was intact; the intestinal mucosa became thinner, and local inflammatory cells had infiltration in MC group. The thickness of intestinal mucosa in CHM, ceftriaxone and CHM+ceftriaxone groups was slightly thicker, and the infiltration of local inflammatory cells was less than that in MC group. The thickness of intestinal mucosa in CHM group and ceftriaxone+CHM group was slightly thicker than that in the ceftriaxone group, and the arrangement was more regular than that in MC group and ceftriaxone group.④Intestinal mucosa permeability and inflammatory state: IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in MC group were higher than those of rats in Sham group [IMII: 4.37±0.56 vs. 0.26±0.29, D-lactic acid (mg/L):12.35±0.83 vs. 7.30±1.29, DAO (kU/L): 2.16±0.43 vs. 0.32±0.06, LPS (kU/L): 0.663±0.012 vs. 0.095±0.003, TNF-α (μg/L): 251.03±82.69 vs. 52.15±6.25, IL-6 (μg/L): 160.50±4.77 vs. 54.30±3.36], while sIgA in MC group was lower than that in Sham group (mg/L: 11.57±0.17 vs. 26.76±1.99). IMII, D-lactic acid, DAO, LPS, TNF-α and IL-6 of rats in CHM, ceftriaxone and CHM+ ceftriaxone groups were significantly lower than those of rats in MC group, while sIgA in CHM, ceftriaxone and CHM+ceftriaxone groups were significantly higher than that of rats in MC group. The change of CHM+ceftriaxone group was more significant than those of CHM group and ceftriaxone group [IMII:1.78±0.23 vs. 1.96±0.62, 3.39±0.43, D-lactic acid (mg/L): 8.56±0.37 vs. 9.62±0.57,11.42±0.39, DAO (kU/L):1.14±0.12 vs. 1.72±0.24, 2.01±0.32, sIgA (mg/L): 25.34±1.49 vs. 23.99±7.85, 17.46±1.20, LPS (kU/L):0.302±0.007 vs. 0.387±0.004, 0.715±0.013, TNF-α (μg/L): 57.10±3.98 vs. 101.49±21.49, 141.91±20.20, IL-6 (μg/L): 93.71±2.39 vs. 87.12±7.31, 104.27±1.84]. Conclusion WPSS therapy may improve the efficacy of antibiotics in the treatment of sepsis by regulating the intestinal flora and reducing the intestinal mucosa permeability and inflammation level.

ObjectiveTo evaluate the effect of Rhubarb associated preparations (rhubarb or prescriptions of traditional Chinese medicine including rhubarb) on sepsis patients with acute gastrointestinal dysfunction (AGI).Methods The retrieval of databases from libraries including PubMed, Medline, Cochrane Central Register of Controlled Trials, CNKI, CBMdisc, Wan Fang Database, VIP database were searched to identify randomized controlled trials (RCTs) about Rhubarb associated preparations for treatment of sepsis patients with AGI from the foundation of the various databases to March 2016. And in the mean time, the references of the studies accepted were also retrieved. The retrieving and screening of literatures were performed independently by two researchers, the methodological quality and data extraction of the enrolled literatures were assessed by Jadad scale, and Cochrane Collaboration 5.3 software was used to perform Meta analyses to observe the effects of rhubarb associated preparations on gastrointestinal function score, acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ) score and 28-day mortality in sepsis patients with AGI; the bias of published literatures was evaluated by funnel plot.Results ① Finally, 16 studies involving 1 171 patients (610 in rhubarb preparation group and 561 in the control group) were identified and enrolled. 12 studies had a Jadad score ≥ 3 and 4 studies < 3. The random method was used in classification of groups in all the studies in which the intergroup baseline data being comparable was clearly indicated. The blind method was applied in 5 contained RCTs.② The results of Meta-analyses showed that rhubarb associated preparation could improve gastrointestinal function score [mean difference (MD) = -0.52, 95% confidence interval (95%CI) = -0.55 to -0.48, P < 0.000 01], reduce the APACHEⅡ score (MD = -3.66, 95%CI = -5.00 to -2.33,P < 0.000 01) and 28-day mortality [odds ratio (OR) = 0.46, 95%CI = 0.30 to 0.71,P < 0.000 01] compared with those in the control group, the differences being statistically significant. No publication bias was seen in 16 literatures containing RCTs from the funnel plot.Conclusions Compared with the control group, the rhubarb associated preparations combined with conventional theraph can significantly improve the gastrointestinal function score, reduce APACHE Ⅱ score and 28-day mortality of sepsis patients with AGI, which suggests the rhubarb associated preparations have better efficacy. In addition, the result of sensitivity analysis has not substantially changed the results of Meta-analysis.

Objective The aim of the study was to evaluate the association of fasting plasma glucose (FPG) level over 5.3 mmol/L to the development of abnormal glucose metabolism and cardiovascular diseases (CVD).Methods This was a retrospective cohort study with 1 064 non-diabetic subjects(980 males;84 females) aged 60 or over, who carried out annual health check-up in Chinese PLA General Hospital from May, 1996 to May, 2015.Based on the average FPG level of 3 years before enrollment, the subjects were divided into four groups : ＜ 5.3 mmol/L, 5.3-＜ 5.6 mmol/L, 5.6-＜ 6.1 mmol/L and 6.1-＜ 7.0 mmol/L.Glucose metabolic changes, complications and mortality were follow-up until May, 2015.Results (1)The initial 3-year average FPG levels were (4.9 ±0.4) mmol/L in the total 1 064 subjects.Among them, 126 subjects developed diabetes mellitus (DM) and 144 subjects developed impaired glucose regulation (IGR) during the follow-up visits.The proportions of IGR and diabetes increased with the FPG levels (P ＜ 0.05).The risk for developing IGR was significantly higher in subjects with FPG≥5.3 mmol/L than in those with FPG ＜ 5.3 mmol/L (RR =3.08, 95％ CI 2.02-4.81, P ＜0.01).The risk for incident DM was markedly increased in subjects with FPG ≥ 5.6 mmol/L than in those with FPG ＜5.6 mmol/L (RR =6.73, 95％ CI 3.90-11.52, P ＜0.01);(2)The risk for CVD was eight folds higher in subjects with FPG ≥5.3 mmol/L than in subjects with FPG ＜ 5.3 mmol/L (RR =8.42,95％ CI 5.11-13.82, P ＜ 0.05);(3) Survival analysis showed that the risk of death was 1.47 times higher in subjects with FPG ≥ 5.3 mmol/L than in subjects with FPG ＜ 5.3 mmol/L after years of followed-up (RR=l.47, 95％CI 1.09-1.98, P=0.0127).Conclusion The risks for IGR, CVD and mortality are higher in the elderly with FPG ≥5.3 mmol/L, which highlights the importance for the disease prevention in elder people with FPG 5.3 mmol/L or more.

Objective To evaluate the safety and effect of one-way barbs line (absorbable sutures v - locTM180) in primary suturing of laparoscopic choledocholithotomy. Methods From July 2014 to June 2015, clinical data of 86 cases performed primary suturing in laparoscopic choledocholithotomy by the same performer were retrospectively analyzed. The patients were divided into three groups, One-way barbs line continuous full-thickness suture group (A group), ordinary absorption line continuous full-thickness suture group (B group) and ordinary absorption line discontinuous full-thickness suture group (C group). The bile duct suture needed time, intraoperative blood loss, postoperative eating time, postoperative hospital stay and postoperative bile fistula were compared. Results All the 86 cases underwent successful operation without T tube, and none of them received alternative open operation. Compared with group B and C, time needed for bile duct suturing in A group have statistical significance. There was no significant difference in the intraoperative blood loss, postoperative eating time, postoperative hospital stay between the three groups (P > 0.05). The incidence of postoperative bile fistula in A group were none. The incidence of postoperative bile fistula in B group was 1 case, the incidence of postoperative bile fistula in C group was 2 cases.Conclusions The method of one-way barbs line continuous full-thickness suture were simple and secure in primary suturing of laparoscopic choledocholithotomy.

OBJECTIVE:To investigate the inhibitory effects mechanism of scallop skirt glycosaminoglycan(SS-GAG)on inju-ry in human umbilical vein endothelium cells (HUVEC). METHODS:In the test,there was a negative control group,a model group and the groups of SS-GAG at high,middle and low concentrations(mass concentrations of 200,100 and 50 mg/L respective-ly). The cells in latter 3 groups were cultured in SS-GAG at different mass concentrations for 12 h,and then in 50 μmol/L oxidized low-density lipoprotein(OX-LDL)for 24 h. MTT method was used to detect cell viability and the activity of lactic dehydrogenase (LDH),the flow cytometer to determine the level of reactive oxygen species (ROS),real-time fluorescence quantitative poly-merase chain reaction (RT-PCR) to detect mRNA expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and Western blot to detect NOX4 protein expression. RESULTS:Compared to the cells in the negative control group,those in the model group demonstrated lower viability,higher activity of LDH,higher level of ROS,and stronger expressions of LOX-1 mRNA and NOX4 protein. There was statistical significance (P<0.01). Compared to the cells in the model group,those in the groups of SS-GAG at high,middle and low concentrations showed higher viability,lower activity of LDH,lower level of ROS and weaker expressions of LOX-1 mRNA and NOX4 protein. There was statistical significance (P<0.01). CONCLUSIONS:SS-GAG can protect HUVEC to some degree by a mechanism which may be related to inhibiting ROS production via LOX-1/NOX4 pathway and relieving oxidative stress injury.

Objective To study the impact of different insulin levels on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2DM),through analysis of different glycometabolism condition among quinquagenarian population.Methods Subjects enrolled were Beijing habitants who received annual physical examination [ including oral glucose tolerance test (OGTI) ] in the Chinese PLA General Hospital from 2005-2007.According to the OGTT results,the subjects were divided into three groups,including normal glucose tolerance-non-hyperinsulinemia group (NGT-NHIns),IGT-hyperinsulinemia group (IGT-Hins) and IGT-non-hyperinsulinemia group (IGT-NHINS).The prognosis between the year 2009 and 2010 of the three groups was observed.Hyperinsulinemia was diagnosed with fasting serum insulin ≥ 15 mU/L and/or 2-hour serum insulin ≥ 80 mU/L after glucose loading.Results The rate of case number of conversion to T2DM in IGT-NHIns group (42/133) was higher than that in IGT-Hins group (24/154) or NGT-NHIns group (12/126).The HOMA insulin resistance index (HOMAIR) of individuals with IGT-NHIns was lower than that of IGT-Hins [ 0.96 (0.40,3.53 ) vs 2.04 (0.59,23.20),P ＜ 0.05 ],while whole body insulin sensitivity index (WBISI) was higher than that of IGT-Hins [ 7.48 (3.20,31.35 ) vs 3.28 ( 0.86,7.67 ),P ＜ 0.05 ].Modified β-cell function index ( MBCI ) and insulin secretion index (ISI) in IGT-NHIns was poorer than that of IGT-Hins respectively [ 2.57 (0.58,10.98) vs5.17(1.04,65.09); 7.66 (0.99,28.40) vs 17.56 (4.18,96.46),allPvalues ＜0.01].Conclusions The risk of IGT-NHIns progressing into T2DM is higher than that of IGT-Hins. For the prevention of T2DM,individuals with IGT-NHIns should be paid more attention than keeping an eye on IGT-Hins patients.Early control of risk factors could protect β cell function and prevent the progression to T2DM.

Eleven old male patients with hyperuricemia were collected ( hyperuricemia group,65-90 years old ).10 healthy middle-aged males ( middle-aged group,30-40 years old) and 10 healthy old males ( older group 60-70 years old ) with normal blood uric acid level were used as controls.All of the subjects were given low purine content diet ( 250 mg/d ) for 3 days followed by high purine content diet ( 800 mg/d ) consecutively for another three days.The samples of fasting blood and 24 h urine were collected for assay.The results showed that there were no significant changes of serum uric acid ( UA ) concentration in three groups after low purine content diet.But the levels of serum UA in three groups all increased significantly after high purine content diet,and the change was higher in hyperuricemia group than middle-aged group [ ( 507.7 ± 108.1 vs 378.9 ± 80.1 ) μmol/L,P＜0.05 ].24 h urine uric acid excretion in three groups was all significantly decreased after low purine content diet and increased after high purine content diet.After high purine content diet,24 h urine uric acid was lower in hyperuricemia group than middle-aged group [ ( 2.99 ± 1.21 vs 3.62 ± 1.02 ) mmol/24 h,P＜0.05 ].Blood urea nitrogen levels in all subjects decreased after low purine content diet and increased after high purine content diet ( P＜0.05 or P＜0.01 ).Creatinine clearance rate in hyperuricemia group was decreased after high purine content diet compared with baseline [ (75.3 ± 20.3 vs 80.7 ±20.0) ml/min ],and there were no significant changes in other groups after low and high purine content diet.24 h urine protein in hyperuricemia group was higher than middle-aged group ( P＜0.05 ),and increased after high purine content diet with significant difference ( P＜0.05 ).These results suggest that high purine content diet and decreased by renal uric acid clearance mainly contribute to hyperuricemia in old people.

Objective To study the correlation between hyperinsulinemia (HIns) and arteriosclerosis in one community in Beijing. Methods Subjects who received arteriosclerosis screening in physical examination annually were studied. All subjects were received 75g oral glucose tolerance test (OGTT) to evaluate glucose metabolic level, and brachial-ankle pulse wave velocity (baPWV) examination to evaluate arteriosclerosis. The correlation between hyperinsulinemia and pulse wave velocity was analyzed. Results Among all the 1046 subjects under investigation, baPWV of subjects with HIns was higher than subjects with normoinsulinemia (NIns) in different glucose metabolism status [normal glucose tolerance, ( 1381.2 ±280. 8) cm/s vs ( 1280. 3 ±218. 7) cm/s; imparied glucose regulation, ( 1557. 5 ±319.3) cm/s vs (1474.7 ±305. 1) cm/s; diabetes, (1764.3 ±476.6) cm/s vs (1664.2 ±374.6)cm/s], especially in subjects with normal glucose tolerance ( P ＜ 0.01 ). The prevalence of cardiovascular risk factors in subjects with HIns was much higher than subjects with NIns ( P ＜ 0.01 ). Multiple logistic regression analysis showed that hyperinsulinemia was the risk factor of arteriosclerosis, and the OR (95%CI) of subjects with HIns was 1.91 (1. 169-3. 105, P ＜0.01 ) as compared to the subjects with NIns. Conclusion The subjects with HIns suffered from much more metabolic risk factors than NIns.Hyperinsulinemia that closely correlated with baPWV was a risk factor of arteriosclerosis.