Objective To investigate microbial characteristics and predisposing factors in gram-negtive bacteria blood stream infection. Methods A descriptive retrospective study was conducted. Patients diagnosed as sepsis with blood culture of G- bacilli and without sepsis were enrolled. The patients were all admitted to ICUs of Guangdong General Hospital from October, 2012 to December, 2014. The clinical characteristics and outcomes were compared. Multiple logistic regression was used to analyse the predisposing factors for sepsis of G- bacilli. Results A total of 148 patients suffered from sepsis of G-bacilli including Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were enrolled. Single-factor analysis showed that patients with sepsis of G- bacilli infection had older ages, higher incidence of coronary heart diseases or congestive heart failure, cerebrovascular diseases or chronic renal insufficiency, hypertension, also higher incidence of longer length of hospital stay before blood was drawn for culture, and higher incidence using of vasoactive agents and pre-admission intravenous antibiotics and lower plasma albumin level (P < 0.05). Conclusions Coronary heart disease or congestive heart failure, chronic renal insufficiency and pre-admission intravenous antibiotics were independent predisposing factors for sepsis of G-bacilli.

Objective To investigate the risk factors and prognosis of blood stream infection in patients of intensive care unit (ICU).Methods Clinical data of all patients with culture-positive sepsis were collected from all ICUs of Guangdong General Hospital from October 12th, 2012 to December 1st, 2014 for retrospective study.Physiological characteristics and laboratory data were compared between patients with blood culture-positive sepsis group and patients without sepsis of control group.Logistic regression analysis was made to identify the risk factors for blood stream infection.Patients with blood culture-positive sepsis group were further divided into survivor and non-survivor groups according to the clinical outcomes.Physiological and laboratory data were compared between two groups.Logistic regression analysis was also performed to identify the risk factors for mortality.Results There were 299 patients with positive blood culture sepsis admitted in the ICUs in two years.Of them, 250 patients infected with Gram positive cocci including staphylococcus haemolyticus, staphylococcus epidermidis, staphylococcus capitis and staphylococcus aureus accounting for the majority.There were 174 patients infected with Gram negative bacilli including acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniaesubsp.pneumoniae accounting for the majority.A univariate analysis demonstrated that there were significant differences in hypertension (P =0.001), diabetes (P =0.01), coronary heart diseases and heart failure (P =0.000), chronic renal insufficiency (P =0.000), prolonged mechanical ventilation (P =0.000), pre-admission intravenous administration of antibiotics (P =0.000), and hypoalbuminemia (P =0.008) between culture positive group and control group.A logistic regression analysis demonstrated that diabetes [OR =2.158, 95％ CI (1.230, 3.787), P =0.007], chronic renal insufficiency [OR =13.410, 95％ CI (1.715, 104.879), P =0.013], pre-admission intravenous administration of antibiotics [OR =8.375, 95％ CI (5.267, 13.317), P=0.000] were independent risk factors for bloodstream infections in ICU.In patients with positive blood culture, the non-survivor group had patients with higher advance of old age, higher rate of hypertension, coronary heart diseases or congestive heart failure, tumor and chronic renal insufficiency, prolonged mechanical ventilation and higher incidence of surgery and pre-admission intravenous administration of antibiotics compared with the survivor group.The advance of old age [OR =1.023, 95％ CI (1.008-1.037), P =0.002], prolonged mechanical ventilation [OR =1.055, 95％ CI (1.024, 1.088), P =0.000] and hypoalbuminemia [OR =0.933, 95％ CI (0.898, 0.971), P =0.001] were independently associated with mortality of bloodstream infection in ICU.Conclusions Diabetes, chronic renal insufficiency and pre-admission intravenous administration of antibiotics were associated with the development of blood stream infection in ICU.The advance of old age, prolonged mechanical ventilation and hypoalbuminemia were independent risk factors for mortality in patients with culture-positive sepsis in ICU.

Objective To investigate effects of physical exercise (PE) on object recognition memory in adult rats of postnatal isoflurane (Iso) exposures.Methods One hundred and ten postnatal 7-day SD rats (P7) were randomly divided into four groups: normal control group (Naive), Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks), Iso group (three times of 2-hour Iso exposure in P7, P9, and P11), and Iso+PE group (received PE in P21 after postnatal Iso exposures). In P67, behavioral testing was conducted including open field and object recognition task (ORT), recording the time (Discrimination Ratios, DR) that rats spent on exploring each object, evaluating effects of PE on object recognition memory.Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05). Compared with Naive, there was no group difference in DR (P>0.05) for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034). Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group:P67,P=0.050,P=0.017; P95,P=0.037,P=0.019); in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036), but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004). Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group:P=0.022,P=0.011); but in P95, the DR of non-Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE:P=0.008,P=0.017).Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These Results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise benefits have gender differences.

Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
Adult ; Amino Acid Sequence ; Animals ; Binding Sites ; Epitopes ; chemistry ; immunology ; metabolism ; Female ; Genotype ; HEK293 Cells ; HLA-A2 Antigen ; metabolism ; Hepatitis B Core Antigens ; chemistry ; immunology ; metabolism ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Middle Aged ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

Objective To investigate the possible presence of radiation brain injury (RBI) in vascular injury and blood-brain barrier (BBB) damage.Methods Seventy 8 weeks old male BALB/C mice were randomly divided into irradiation group and control group;mice in the two groups received whole-brain exposure with a single dose of 10 Gy irradiation or sham irradiation.Tissue samples were taken 1,7,30,90 and 180 days after irradiation (7 mice in each time point per group);HE staining was used to observe the microvascular morphology and density changes;immune-fluorescence staining was used to visualize the differential expressions of factor Ⅷ related antigen (vWF) and zonulaoccludens-1 (ZO-1).Results Micro-vascular disorders began to appear from the first day of irradiation,deteriorating with time extension gradually.After the X-ray irradiation exposure,the protein expressions of vWF and ZO-1 in the irradiation group were significantly decreased as compared with those in the control group 1,7,30,90 and 180 days after irradiation (vWF:23.17±2.93 vs 15.80±2.39,21.25±2.33 vs 11.60±2.3,19.78±2.16 vs 8.20±1.64,17.21±3.31 vs 6.00±2.12 and 16.98±1.92 vs 3.80±2.59;ZO1:26.17±3.31 vs 15.40±1.82,23.20±2.93 vs 12.00±1.58,20.88±2.20 vs 9.10±2.55,18.32±1.87 vs 6.20±1.92 and 17.50±1.91 vs 2.40±1.52,P＜0.05);besides,the decreased expression ofvWF and ZO-1 in the irradiation group showed a time-depended manner,with significant differences between each two time points (P＜0.05).Conclusion X-rays may induce persistent micro-vascular injury and destroyed BBB tight junctions,which may be closely related to the occurrence and development of RBI.

Cholelithiasis is a kind of common and multiple diseases.In recent years,traditional laparotomy has been challenged by a minimally invasive surgery.Through literature review,the therapeutic method,effect,and complications of minimally invasive treatment of intrahepatic and extrahepatic bile duct stones by combining our practical experience were summarized as follows.(1) For intrahepatic bile duct stones,the operation may be selected by laparoscopic liver resection,laparoscopic common bile duct exploration (LCBDE),or percutaneous transhepatic cholangioscopy.(2) For concomitant gallstones and common bile duct stones,the surgical approach can be selected as follows:laparoscopic cholecystectomy (LC) combined with endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilatation,LC plus laparoscopic transcystic common bile duct exploration,LC plus LCBDE,and T-tube drainage or primary suture.(3) For concomitant intrahepatic and extrahepatic bile duct stones,laparoscopic liver resection,choledochoscopy through the hepatic duct orifice on the hepatectomy cross section,LCBDE,EST,and percutaneous transhepatic cholangioscopic lithotripsy could be used.According to the abovementioned principle,the minimally invasive treatment approach combined with the surgical technique and equipment condition will be significant in improving the therapeutic effect and avoiding the postoperative complications or hidden dangers of intrahepatic and extrahepatic bile duct stones.

Objective To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition(MMT)of peritoneal mesothelial cells(HMrSV5),and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3(STAT3)on rat peritoneal fibrosis(PF)model.Methods The animals were divided into three groups:the sham group,the model group,and the STAT3 inhibitor group.A miniature per-itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate.After 10 weeks,HE staining was used to evaluate the histology of the peritoneum,and the level of transforming growth factor-β1(TGF-β1)in the peritoneum was measured by immuno-histochemistry.HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot.High glucose was used to stimulate HMrSV5 after successful transfection with si-STAT3 and Western blot was used to measure the protein level of STAT3,p-STAT3,and the key enzymes of glycol-ysis 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)and lactate dehydrogenase A(LDHA).Results HE staining showed that administration of STAT3 inhibitor(BP-1-102)could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats.The expression of TGF-β1 in the rats perito-neum of the model group was significantly higher than that in the sham group,and the level of TGF-β1 was marked-ly lower in the STAT3 inhibitor group compared to the model group(P<0.05).Compared to the control group,high glucose induced the up-regulation of α-smooth muscle actin(α-SMA),the down-regulation of E-cadherin and STAT3 activation in HMrSV5(P<0.05).Mesothelial cells treated with high glucose also exhibited high expres-sion of the key enzymes of glycolysis(PFKFB3,LDHA)(P<0.05),and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose(P<0.05).Conclusion STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT,and targeting STAT3 alleviates peritoneal fibrosis and an-giogenesis during peritoneal dialysis treatment in rats.

Histopathology is still the golden standard for the diagnosis of clinical diseases. Whole slide image (WSI) can make up for the shortcomings of traditional glass slices, such as easy damage, difficult retrieval and poor diagnostic repeatability, but it also brings huge workload. Artificial intelligence (AI) assisted pathologist's WSI analysis can solve the problem of low efficiency and improve the consistency of diagnosis. Among them, the convolution neural network (CNN) algorithm is the most widely used. This article aims to review the reported application of CNN in WSI image analysis, summarizes the development trend of CNN in the field of pathology and makes a prospect.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.

Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.