Intestinal flora is closely associated with chronic hepatitis B (CHB). Recent studies have shown that the imbalance of intestinal flora is associated with the development, progression, and prognosis of CHB, and the environment of intestinal flora may also change with disease progression, suggesting that intestinal flora and CHB interact with each other. This article reviews the influence of intestinal flora on the progression of CHB and related liver diseases and the role of intestinal flora regulation in the diagnosis and treatment of CHB and related liver diseases, in order to provide new ideas for the clinical treatment of CHB.

Diabetic nephropathy (DN) is considered the primary causes of end-stage renal disease (ESRD) and is related to abnormal glycolipid metabolism, hemodynamic abnormalities, oxidative stress and chronic inflammation. Antagonism of vascular endothelial growth factor B (VEGF-B) could efficiently ameliorate DN by reducing renal lipotoxicity. However, this pharmacological strategy is far from satisfactory, as it ignores numerous pathogenic factors, including anomalous reactive oxygen species (ROS) generation and inflammatory responses. We found that the upregulation of VEGF-B and downregulation of interleukin-22 (IL-22) among DN patients were significantly associated with the progression of DN. Thus, we hypothesized that a combination of a VEGF-B antibody and IL-22 could protect against DN not only by regulating glycolipid metabolism but also by reducing the accumulation of inflammation and ROS. To meet these challenges, a novel anti-VEGFB/IL22 fusion protein was developed, and its therapeutic effects on DN were further studied. We found that the anti-VEGFB/IL22 fusion protein reduced renal lipid accumulation by inhibiting the expression of fatty acid transport proteins and ameliorated inflammatory responses

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.
Animals ; Dentate Gyrus ; Dopamine ; Hippocampus ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; Spatial Memory

Objective:To investigate the indication of pre-cut-endoscopic mucosal resection (pre-cut-EMR) on the treatment of colorectal laterally spreading tumors (LSTs).Methods:A retrospective study was performed on data of colorectal LSTs patients, who underwent pre-cut-EMR in Wuxi Second People’s Hospital and Zhongshan Hospital from January 2014 to June 2019. The relationships between the clinical characteristics of the lesions and the success rate and complications of pre-cut-EMR were analyzed.Results:Data of 132 colorectal LSTs cases were included in the study. Morphology of 29 (22.0%) LSTs were homogeneous granular type, 43 (32.6%) LSTs were mixed non-granular type, 58 (43.9%) LSTs were flat elevated type, and 2 (1.5%) LSTs were pseudo-depressed type. The diameter of lesions was 2.3±1.5 cm (ranged from 2.0 cm to 5.0 cm). Among the 132 LSTs, 36 (27.3%) tumors were located in rectum, 15 (11.4%) in sigmoid colon, 10 (7.6%) in descending colon, 17 (12.9%) in splenic flexure of colon, 21 (15.9%) in transverse colon, 24 (18.2%) in hepatic flexure of colon, 6 (4.5%) in ascending colon, and 3 (2.3%) in cecum. The histopathological diagnoses of the 132 LSTs included low grade intraepithelial neoplasia in 58 cases (43.9%), high grade intraepithelial neoplasia in 69 cases (52.3%), intramucosal carcinoma in 2 cases (1.5%), and canceration in 3 cases (2.3%). Pre-cut-EMR was achieved in all 132 patients, and the operation time was 25.3±13.6 min (ranged 20-65 min). The rate of en bloc resection and complete resection were 95.5% (126/132) and 100.0% (132/132), respectively. Two cases (1.5%) had intraoperative perforation, and were both located in the sigmoid colon with the diameter of 4.0 cm and 4.5 cm, respectively. Twelve cases (9.0%) had immediate bleeding during operation, and 2 cases (1.5%) had delayed bleeding after operation. Patients had been followed up for 6-24 months, the wound healed well after operation, and no local recurrence was found.Conclusion:Pre-cut-EMR is an effective and safe therapy for colorectal LSTs with diameter less than 4.0 cm.

Objective To investigate the characteristics of gut microbiota dysbosis in septic and non-septic patients in ICU.Methods A prospective observational research was conducted.Ten septic patients(septic group),ten patients without sepsis(non-septic group) were admitted to Department of Critical Care Medicine of General Hospital of Ningxia Medical University from February 2017 to June 2017 were enrolled.And ten healthy persons was enrolled as control group.Stool samples were collected from septic and non-septic patients within two days following admission to the intensive care unit (ICU);healthy persons' was random.High throughput 16S rRNA gene sequencing technology was used to detect fecal bacterium of three groups.Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score,Sequential Organ Failure Assessment (SOFA) score of patients were recorded on the first day after admission to ICU.Results Compared with the control group,the α diversity of gut microbiota in non-septic and septic groups showed a downward trend,the [3 diversity showed that the structure of gut microbiota in non-septic and the septic groups was significant different,and the individual differences were more obvious.At the level of phylum,compared with the control group,the proportion of Firmicutes+Bacteroidetes in non-septic and septic groups decreased significantly(P=0.013,0.028),and the proportion of Proteobacteria increased(P=0.017,0.026),while the proportion of Fusobacteria just increased in the non-septic group(P ＜ 0.01).At the level of genus,compared with the control group,the proportion of beneficial symbiotic genus in non-septic and septic groups can be seen decreased,such as Ruminococcus(P=0.045,0.026),Pseudobutyrivibrio(P=0.009,＜ 0.01),Anaerostipes(P=0.011,0.003),Coprococcus(P=0.045,0.011),Phascolarctobacterium(P=0.008,0.022),Subdoligranulum(P=0.006,0.026).The proportion of Lactobacillus,Dorea,Faecalibacterium,Roseburia and Blautia showed downward trend in non-septic and septic groups,but only the decline of Lactobacillus in non-septic group had statistical difference(P=0.005),and the decline of Dorea,Faecalibacterium,Roseburia and Blautia in septic group had statistical differences(P=0.037,0.038,0.002 and 0.017,respectively).The proportion of conditional pathogenic Fusobacterium,Actinomyces,Peptstreptococcus,Streptococcus increased in non-septic group(P=0.001,0.019,0.011 and 0.014,respectively),the proportion of pathogenic Staphylococcus(P=0.035,0.006),Enterococcus(P=0.001,0.001),Anaerococcus(P=0.006,0.006) and Bacillus(both P ＜ 0.01) increased in non-septic and septic groups.Conclusions Gut microbiota dysbiosis occured in septic and non-septic patients in the ICU,and showed that diversity decreased,structure of intestinal flora changed,obligate anaerobic bacteria decreased,facultative anaerobic bacteria increased,benefical symbiotic bacteria decreased,pathogenic bacteria increased and can be the dominate genus.

OBJECTIVETo analyze the risk factors of carcinogenesis of large colorectal polyps (diameter ≥ 10 mm) found by colonoscopy.

METHODSClinicopathological and follow-up data of 418 consecutive patients who were diagnosed as colorectal polyps with diameter≥10 mm by colonoscopy at two endoscopy centers of the Affiliated Wuxi Second People's Hospital, Nanjing Medical University (n=207) and Zhongshan Hospital, Fudan University (n=211) from January 2015 to December 2016 were retrospectively collected. High-grade intraepithelial neoplasia and cancer were defined as malignancy in this study. Chi square test was used for univariate analysis, and logistic regression was used for multivariate analysis (in patients with multiple polyps, if the pathological findings were all low grade intraepithelial neoplasia, one polyp with the largest diameter was selected to enter the model; in patients with high grade intraepithelial neoplasia, one polyp of high grade intraepithelial neoplasia with the largest diameter was selected to enter the model). Associated risk factors of malignancy were analyzed.

RESULTSAmong the 418 patients, 278(66.5%) were male and 140(33.5%) were female, with mean age of (58.7±10.2) (range 15-87) years old. Of 398 patients undergoing endoscopic treatment with resected 456 polyps, 142 cases with 150 polyps were malignant, including 134 polyps of high-grade intraepithelial neoplasia and 16 polyps of intra-mucosal cancer. The other 20 patients showed negative elevation signs after endoscopic submucosal injection and were transferred to surgery, of whom 20 polyps were resected. Histological examination of these 20 polyps indicated invasive cancer. Univariate analysis showed that age ≥ 50 years [40.5% (150/370) vs. 25.0% (12/48), χ² =4.323, P=0.041], multiple polyps [77.5%(31/40) vs. 34.7%(131/378), χ² =12.900, P=0.001], polyp locating at rectum [59.0%(36/61) vs. 32.3%(134/415), χ² =22.736, P=0.000], polyp diameter ≥31 mm [74.1%(20/27) vs. 33.4%(150/449), χ² =36.493, P=0.000] and tubular villous adenoma [67.4%(120/178) vs. 16.8%(50/298), χ² =71.810, P=0.000] were associated with malignancy. Multivariate analysis showed that age ≥ 50 years(OR=2.473, 95%CI:1.209-5.058, P=0.013), multiple polyps (OR=2.472, 95%CI: 1.300-4.702, P=0.006), polyp locating at rectum (OR=1.253, 95%CI: 1.091-1.439, P=0.001) and the polyp diameter ≥31 mm (OR=1.500, 95%CI:1.196-1.881, P=0.000) were independent risk factors for malignancy of large colorectal polyps. The mean follow-up time was (9.6±4.2) months. During the follow-up period, 86 patients (20.5%) who received endoscopic resection developed recurrent adenoma which all were successfully removed by colonoscopic polypectomy. Two patients(0.5%) developed colon cancer 6 months after endoscopic resection and both underwent radical surgery and chemotherapy. Their previous pathology from endoscopic resection was tubular villous adenoma and high grade intraepithelial neoplasia. All the patients were alive during the follow-up period.

CONCLUSIONSAge ≥50 years old, multiple polyps, polyps locating at rectum and polyps with diameter ≥ 31 mm are the risk factors of malignancy. Emphasized examination should be recommended for those with the above mentioned risk factors to avoid missed diagnosis and misdiagnosis. The choice of endoscopic treatment must be reasonable for curative resection.

Objective To observe the effect of vancomycin-loaded calcium sulfate for one-stage treatment of chronic osteomyelitis.Methods A retrospective case series study was made on 26 patients with chronic osteomyelitis treated from January 2014 to April 2016.There were 23 males and 3 females,with a mean age of 35.8 years (range,16-90 years).After focus debridement of osteomyelitis,the cavities were filled with vancomycin-loaded calcium sulfate and systemic antibiotics were used.Meanwhile,gentamicin was added to patients showing unclear pathogens.Three patients underwent flap transfer surgery simultaneously due to the inadequate soft tissue coverage.Wound healing,local redness and swelling,sinus recurrence,recovery of osteomyelitis and repair of bone defect were detected after operation.Results All patients were followed up for 6-30 months (mean,19.5 months).Primary healing was achieved in all patients.One patient experienced wound exudate and was effectively managed by dressing change,one patient experienced inadequate local soft tissue coverage and was effectively managed by a second flap transfer surgery,and one patient remained wound unhealing after two surgeries and was cured by infected bone resection using the Masquelet induced membrane technique.Follow-up showed local bone defect was repaired in all patients without bone infection recurrence.Conclusions For patients with chronic osteomyelitis,one-stage surgery with vancomycin-loaded calcium sulfate can control infection with simultaneous repair of bone defect.Therefore,the procedure is a simple and effective method and worthy of clinical practice.

BACKGROUND:There is no effective drug for idiopathic pulmonary fibrosis (IPF), because of a lack of the animal model imitating the complete pathogenesis of human IPF. Therefore, it is critical to establish an ideal animal IPF model used for investigating the underlying pathogenesis and developing a kind of effective drug. OBJECTIVE:To establish an animal model that can mimic more characters of human IPF. METHODS:Seventy male C57BL/6 mice were randomly divided into two groups, fol owed by subjected to the intraperitoneal injection of bleomycin (35 mg/kg) on days 1, 4, 8, 11, 15, 18, 22, and 25, twice (group A) or once (group B) a week. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the eighth injection, and the lung tissues were moved used for hematoxylin-eosin, Masson and immunohistochemical stainings. RESULTS AND CONCLUSION:There were various degrees of alveolitis and pulmonary fibrosis in the two groups at different time points after the last injection. The scores of alveolitis and pulmonary fibrosis in the group A began to gradual y increase from the 2nd week and reached the highest level at the 6th-8th weeks until the 10th week. In contrast, the scores of alveolitis and pulmonary fibrosis in the group B peaked at the 2nd week, then fluctuately decreased, and were significantly lower than those in the group A at the 6th week (P<0.05). Immunohistochemistry showed that type I col agen deposition was mainly distributed in the subpleural region, peri-vascular region and alveolar septa, which was consistent with Masson staining findings. The expression levels of transforming growth factorβ1 (TGF-β1) andα-smooth muscle actin (α-SMA) in the regions developing alveolitis and pulmonary fibrosis were significantly increased. In the group A, the expression levels of type I col agen, TGF-β1,α-SMA, and the hydroxyproline content in the lung tissues reached the peak level at 6-8 weeks. However, in the group B, al above indicators reached the highest level at the 2nd week, but gradual y decreased thereafter. At the 4th week, the expression Levels of TGF-β1 andα-SMA in the group B were significantly lower than those in the group A (P<0.05). At the 6th week, the hydroxyproline and type I col agen levels in the group B were significantly lower than those in the group A (P<0.05). In conclusion, the mouse model of pulmonary fibrosis induced by intraperitoneal injection of 35 mg/kg bleomycin twice weekly can be used to mimic the repetitive wound healing process, pathological morphology and cytokine changes of human IPF, which is prone to administration, with better stability and repeatability. This model is of great significance for the study on IPF. Subject headings:Disease Models, Animal;Pulmonary Fibrosis;Bleomycin

OBJECTIVETo determine the feasibility, safety and short-time efficacy of narrow-band imaging (NBI) combined with endoscopic submucosal dissection (ESD) for treating gastric high grade intraepithelial neoplasia (HGIN).

METHODSClinical data of 78 patients with gastric HGIN diagnosed by gastroscope and pathology undergoing NBI combined with ESD at Wuxi No.2 People's Hospital and Zhongshan Hospital of Fudan University from January 2014 to December 2015 were retrospectively analyzed. Their clinicopathological and follow-up data were analyzed.

RESULTSThere were 47 males and 31 females aged from 38 to 85 years old. Preoperative NBI showed that lesions of all the 78(100%) patients had clear resection margin, and 91%(71/78) lesions had abundant vessels in the central depression area. One case was converted to open abdominal operation due to intra-operational perforation, 77(98.7%) gastric HGIN lesions were successfully dissected under ESD, including 74 cases(94.9%) of en bloc dissection, and other 3 cases with severe adhesion of submucosa whose lesion wound after ESD was treated with argon plasma coagulation(APC). The mean maximum diameter of the lesion size was (1.2±0.8) cm. The average operation time was(48±21) minutes. Delayed hemorrhage occurred in 5 cases(6.4%) who were also treated successfully by endoscopic hemostasis. Postoperational pathology revealed en bloc dissection rate was 91.0%(71/78), positive rate of resection margin was 3.8%(3/78), and healing dissection rate was 89.7%(70/78). Thirty-two lesions (41.0%) remained the diagnosis as HGIN, 6 lesions(7.7%) were diagnosed as low grade intraepithelial neoplasia, and 40 lesions (51.3%) were diagnosed as adenocarcinoma. Fifty-seven cases were followed up for 12 months, 21 cases were followed up for 6 months, and there was no recurrence in those 3 patients with positive margin. Two cases (2.6%) relapsed and were diagnosed as adenocarcinoma by repeat pathology examination.

CONCLUSIONNBI combined with ESD for diagnosis and treatment of gastric HGIN is safe and effective, and can achieve en bloc complete resection of the lesions with a low complication rate.

Adenocarcinoma ; surgery ; Adult ; Aged ; Aged, 80 and over ; Carcinoma in Situ ; surgery ; Dissection ; Endoscopy ; Female ; Hemostasis, Endoscopic ; Humans ; Male ; Middle Aged ; Narrow Band Imaging ; Neoplasm Recurrence, Local ; Operative Time ; Retrospective Studies ; Stomach Neoplasms ; surgery

OBJECTIVETo explore the concentration-response relationship between ambient concentration of PM2.5 and daily total hospital emergency room visits in Beijing during 2012 and 2013. This study also examined the effects of ambient PM2.5 during heavy polluted days on emergency room visits compared with the light polluted days.

METHODSWe collected the daily meteorological factors monitoring data and concentrations of air pollutants in Beijing during October 1, 2012 to December 31, 2013. We also collected the daily emergency room visits from a tertiary hospital in Beijing in the same time period. Generalized additive model was fitted to estimate the association between the ambient PM2.5 and the hospital emergency room visits, by using the smooth function to adjust long term trend of time, public holidays and day of week. In addition, constrained piecewise linear function was then used to estimate the excess risk for different segment of concentration-response function.

RESULTSThe annual average concentration of PM2.5 was 90.9 µg/m(3) during October 1, 2012 and December 31, 2013. There were total 64 260 cases for total emergency room visits, of which respiratory disease had 9 849 cases and cardiovascular disease had 11 168 cases. PM2.5 was positive related with PM10, NO2 and SO2. The corresponding correlation coefficients were 0.87, 0.78 and 0.62, respectively (P<0.05). And PM2.5 was positively related with relative humidity, with correlation coefficient 0.45 (P<0.05). But PM2.5 was negatively related with mean temperature (r=-0.17, P< 0.05) and wind speed (- 0.32, P<0.05). In the single polluted model, after adjusting the effects of temperature, relative humidity and wind, every 10 µg/m(3) increase of concentration of ambient PM2.5, the corresponding excess risk of daily emergency room visits was 0.25% (95% CI: 0.07-0.43). In the two-pollutant model PM2.5+SO2 and PM2.5+NO2, every 10 µg/m(3) increase of concentration of ambient PM2.5, the corresponding excess risk of daily emergency room visits were 1.07% (95%CI:0.83-1.30) and 0.56% (95%CI: 0.32-0.80) respectively, which were higher than the effect in single pollutant model. Average concentration of ambient particulate matters (PM2.5) was 204.16 µg/m(3) during heavy pollution, higher than control period (85.24 µg/m(3)). When PM2.5 as the primary air pollutants during heavy polluted days, we observed a significant increase in emergency room visits, and the odd ratios was 1.16 (95% CI:1.09-1.22).

CONCLUSIONThere were positive correlation between high concentration of ambient particulate matters (PM2.5) and increasing daily emergency room visits. Especially during the heavy polluted days, the effects of elevated concentration of PM2.5 on hospital emergency room visits were much larger.

Air Pollutants ; analysis ; Beijing ; Cardiovascular Diseases ; diagnosis ; Emergency Service, Hospital ; statistics & numerical data ; Humans ; Meteorological Concepts ; Particulate Matter ; analysis ; Respiratory Tract Diseases ; diagnosis ; Temperature ; Tertiary Care Centers