Objective To evaluate the clinical efficiency and safety of thiazolidinediones (TZDs) on treat-ment of patients with nonalcoholic fatty liver disease (NAFLD). Methods The published controlled clinical trials about TZDs on treatment of patients with NAFLD from 1998 to 2008 were identified by searching in the full-text data base,such as Medline, PubMed, Ovid, EMCC, CBM Disc, CNKI, Wanfang, Weipu data and so on, as well as by searching of cross references from original articles and reviews. The enrollment standard was formulated strictly ac-cording to the designs of trials, and Meta analysis was performed by software package of Review Manage 4.2. Further-more, the statistic test, sensitivity and publication bias about the combined statistic data were revealed by referring to forest-graph and funnel-plot. Results All of the 473 patients in 18 controlled clinical trials were enrolled in this study. The weighted mean diffrerence of serum ALT, AST,TC,TG and BMI, HOMA-IR before and after treatment with TZDs 32. 24 (18.98-45.49) (Z=4.77,P<0.05),20.32 (2.30-38.35) (Z=2.21,P<0.05),0.26 (-0.01-0.54)(Z=1.88,P=0.06),0.63 (0.33-0.93) (Z=4.14,P<0.01),and -0.06 (-0.66-0.55) (Z=0.19, P=0.85),2.63 (1.33-3.93) (Z=3.96, P<0.01). In all papers, the improvement of hepatic tissue after treatment with TZDs in patients with NAFLD was observed in only 6 articles, which demonstrated the hepatic steatosis, inflammation and fibrosis [WMD (95% CI) 1.59 (1.08-2.10), 1.45 (0.90-2.00), 0.72 (0.12-1.32), Z= 6.08,5.16,2.33,P<0.05],especially the degree of NASH activity index,whose WMD (95% CI) was 4.21 (3.13-5.28) and Z=7.66,P<0.01, were improved significantly in the 104 NASH patients taken this kinds of drugs. There were 7 patients exiting from the all chnical trial, and the main adverse effects in patients accepting treat-ment with TZDs were debility, dizziness, edema of lower extremity, weight gain, indisposition of gastrointestinal tract, elevated liver enzyme and so on, which were similar to the control group. Conclusions The therapeutic effects of TZDs on NAFLD is confirmed. Not only are the serum liver enzyme,TC,TG and HOMA-IR in patients with NAFLD improved, but this new euglycemic agent has no acutely adverse effect in clinical application,which confirms the clin-ical efficiency and safety of TZDs on treatment of patients with NAFLD.

OBJECTIVE To evaluate the spectrum of imipenem-resistant Pseudomnas aeruginosa and the production of metallo-?-lactamase.METHODS The clinical strains of P.aeruginosa were collected from Jan to Dec 2007.The results of antimicrobial susceptibility tests and detection of metallo-?-lactamase were analyzed.Antimicrobial susceptibility tests were performed by K-B methods;the production of metallo-?-lactamase was tested by CAZ-EDTA synergy method.RESULTS Sixty strains were isolated,imipenem-sensitive and resistant strains were 40(66.7%) and 20(33.3%),respectively,and 7 strains with metallo-?-lactamase were detected.Among imipenem-resistant strains,at least 90.0% strains were resistant to meropenem,gentamicin,tobramycin,ciprofloxacin and SMZ-TMP;at least 80.0% strains were resistant to piperacillin and piperacillin/tazobactam;50.0% strains were resistant to ceftazidime and cefepime;polymyxin E was less resistant than others.Twenty strains were resistant to at least 3 antimicrobial agents,which was obviously higher than 27.5% of imipenem-resistant strains.CONCLUSIONS The resistance rate of imipenem-resistant P.aeruginosa is higher than imipenem-sensitive ones.The production of metallo-?-lactamase is one of the mechanisms of P.aeruginosa resistance to imipenem and shou1d be detected carefully,which could help us medicate reasonably in clinic and avoid using medicine which could induce and strengthen the resistance.

Objective To investigate the association of SLC34A1 ( rs6420094 ) and RGS14 (rs4074995) polymorphisms with serum level of phosphorus in chronic hepatitis B virus (HBV) infection patients following long-term adefovir dipivoxil ( ADV ) treatment.Methods Ninety one patients with chronic HBV infections admitted in Third Hospital of Hebei Medical University during October 2012 and August 2013 were enrolled in the study.All patients received ADV treatment ( monotherapy or combination therapy) for at least two years, among whom 31 had hypophosphatemia and 60 had normal serum phosphorus levels.rs6420094 and rs4074995 were genotyped by polymerase chain reaction-restrictive fragment length polymorphism ( PCR-RFLP ) analysis.The relationship between allele frequency and serum phosphorus concentration was analyzed by Chi-Square test.Results In hypophosphatemia group, there were 13, 13, and 5 patients with genotype A/A, A/G and G/G at rs6420094, respectively;while in patients with normal serum phosphorus levels, there were 35, 24 and 1 patients with genotype A/A, A/G and G/G at rs6420094.The frequency of allele A at rs6420094 in patients with normal serum level of phosphorus was higher than that in hypophosphatemia group ( 78.3% vs.62.9%, χ2 =4.947, P <0.05 ).In hypophosphatemia group, there were 2, 11, and 18 patients with genotype A/A, A/G and G/G at rs4074995, respectively;while in patients with normal serum phosphorus level, there were 1, 21 and 38 patients with genotype A/A, A/G and G/G at rs6420094.There was no difference in the frequencies of alleles at rs4074995 between two groups (χ2 =0.625, P >0.05).Conclusion The polymorphism of rs6420094 gene may be associated with the serum level of phosphorus in patients with chronic HBV infections following long-term treatment of ADV.

Objective: To analyze the spatio-temporal distribution of pulmonary tuberculosis (PTB) among students in Suzhou City, Jiangsu Province from 2015 to 2023, so as to provide the evidence for the prevention and control of PTB in schools. Methods: Data of PTB cases among students in Suzhou City from 2015 to 2023 were collected from Chinese Disease Prevention and Control Information System and Suzhou Report of Investigation and Disposal of Tuberculosis in Schools. The seasonal incidence of PTB among students was analyzed using seasonal index (SI). The spatio-temporal clustering characteristics of PTB among students were analyzed using spatial autocorrelation and retrospective spatio-temporal permutation scanning. Results: Totally 1 374 PTB cases among students were reported in Suzhou City from 2015 to 2023. PTB cases were reported in each month, and the SIs were 100.69%, 124.38%, 108.98%, 135.04%, 106.61% and 106.61% in April, May, July, September, October and November, respectively, indicating the prevalence of PTB among students. Spatial autocorrelation analysis showed there was a positive spatial correlation of PTB among students in 2019 and 2020 (Moran's I=0.053 and 0.089, both P<0.05). From 2015 to 2023, there were high-high clustering sites mainly in Hengtang Street and Shishan Street. Retrospective spatio-temporal permutation scanning showed a primary cluster in Hengtang Street, with aggregation time in 2017, and 6 secondary clusters covering 25 towns (streets). Conclusion From 2015 to 2023, the PTB cases among students in Suzhou City were mainly concentrated in summer and autumn, and were predominantly clustered in Hengtang Street and Shishan Street.

Objective Identify novel protein kinase Cε(nPKCε)-interacted proteins in the cortex of hypoxic preconditioned mice.Methods Immunoprecipitation (IP) and two-dimensional electrophoresis (2-DE) combining with ImageMaster 2D Platinum software were applied to analyze the differential expressions of nPKCe-interacted proteins;the target protein spots were identified by matrix-associated laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and Western blot.Results Compared with control group,there were 34 upregulated protein spots and 20 downregulated protein spots in cytosolic fraction,while 27 upregulated prtein spots and 28 downregulated protein spots were determined in particulate fraction of cerebral cortex of HPC mice.The levels of nPKCε-interacted HSP 70 and 14-3-3γ/protein expressions increased significantly in both cytosolic and particulate fractions;but the protein level of nPKCε-interacted HSP60 increased only in particulate fraction of cerebral cortex of HPC mice.Conclusion nPKCε might be involved in the development of cerebral HPC via the regulation of its interacted proteins such as HSP60,HSP70 and 14-3-3γ.

Objective To study the profile of peripheral blood cortisol concentration in patients with hepatitis B virus (HBV)-related acute on chronic liver failure (ACLF) and its association with disease severity and predictive value on prognosis.Methods Forty-five patients with HBV-related ACLF,including 15 patients in early-stage,15 in medium stage and 15 in end-stage; and 15 patients with severe chronic hepatitis B (CHB) were also enrolled.Peripheral blood cortisol concentration was tested by chemiluminesence immunoassay.SPSS version 18.0 was used to compare peripheral blood cortisol concentration among different groups and analyze its correlation with prothrombin activity (PTA),total bilirubin (TBil),albumin (Alb),alanine aminotransferase (ALT),aspartate aminotransferase (AST),HBV DNA,international normalized ratio (INR) and model for end-stage liver disease (MELD) scores.The independent risk factors of prognosis in patients with HBV-related ACLF were determined by performing Logistic regression analysis.Results The concentrations of peripheral blood cortisol in severe CHB group,early stage ACLF group,medium stage ACLF group and end-stage ACLF group were (595.6±114.0),(496.0±87.2),(303.9±81.1),and (183.8±71.8) nmol/L,respectively.A decreasing trend was observed and the differences among groups were statistically significant (F =63.93,P ＜ 0.01).Peripheral blood cortisol concentration were significantly different among subgroups of patients with MELD＜30,followed by 30-40 and ＞40(F 9.01,P＜0.01).Peripheral blood cortisol concentration in patients with ACLF was positively correlated with PTA level (r=0.83,P＜0.01),and inversely correlated with TBil (r =-0.34,P＜0.05),MELDscore (r =-0.60,P＜0.01),AST/ALT (r =-0.35,P＜0.05),and INR (r=-0.59,P＜0.01).Association with Alb,ALT,AST and HBV DNA was not observed.According to multivariate Logistic regression analysis,MELD score,cortisol level,Alb and total cholesterol were independent risk factors of prognosis for patients with ACLF.Serum cortisol concentration in survival group of HBV-related ACLF was higher than that in death group,while the death group exhibited a gradually decreasing trend.Conclusions The peripheral blood cortisol concentration decreases in patients with HBV-related ACLF,which is related to the degree of liver dysfunction,disease severity and prognosis of patients.Moreover,the lower level of cortisol concentration indicates poor short-term prognosis in patients with HBV related ACLF.

Objective To detect the gene mutation of thyroid hormone receptor β ( TRβ ) in a family with thyroid hormone resistance syndrome.Methods The genomic DNA was extracted from peripheral blood leukocytes of the patient and his 5 family members.The exons 1-10 ofTRβ gene were amplified by PCR.The products of PCR were sequenced directly to detect the gene mutation.Results Two members of this family were confirmed to have the C y A transition mutation at nucleotide 1642 site within exon 10 of TRβ gene,which was a missense mutation causing the substitution of Proline to Threonine (P453T).The mutation was Heterozygous.Conclusions It was confirmed that the patient has TRβ gene mutation P453T in exon 10.The mutation may lead to the occurrence of thyroid hormone resistance syndrome.

Objective To investigate the differences of expression and activation of natural killer (NK) cell G2D (NKG2D) in patients with different immune status of chronic hepatitis B virus (HBV) infection, and to explore the significance of NKG2D-mediated immune injury in HBV infection.Methods Fifteen chronic HBV carriers (immune tolerance),15 chronic hepatitis B (CHB, immune activation) patients, 15 HBV-related acute/subacute-on-chronic liver failure (HBV-ACLF, immune over-activation) patients were enro1led in this study from January 2010 to December 2011 in the Third Hospital of Hebei Medical University.The frequencies of NK cells and NKG2D+ NK cells in peripheral blood mononuclear cells (PBMC) were detected by flow cytometry.The NKG2D mRNA expressions were measured by real-time fluorescent quantitative polymerase chain reaction.Localization and hemi-quantitative analysis of NKG2D+ cells in liver tissue were performed by immunohistochemistry staining.Concentrations of serum interferon(IFN)-γ, tumor necrosis factor(TNF)-α, perforin and granzyme B were quantified by enzyme 1inked immunosorbent assay (ELISA).Normally distributed continuous variables were analyzed using one-way analysis of variance (ANOVA), followed by Student-Newman-Keuls q test for evaluating variances between each two groups.For non-normally distributed data or heterogeneity of variance, differences between groups were analyzed using nonparametric Kruskal-Wallis H test, followed by Nemenyi test for pairwise comparisons.Pearson chi-square test was used to analyze categorical variables.Results The percentages of NK cells in PBMC were (13.58±3.24)% in healthy controls, (5.42±2.18)% in chronic HBV carriers, (7.92±2.85)% in HBV-ACLF group and (8.43±2.92)% in CHB group.The percentage of NK cells in PBMCs was lower in each chronic HBV-infected group compared with healthy controls (F=22.04, P<0.05).The frequency of NKG2D+ NK cells in HBV-ACLF group (18.92±5.85)% was the highest, followed by CHB group (12.85±3.39)%, healthy controls (8.45±2.86)%, and chronic HBV carriers (3.36±1.05%), with the statistically significant differences between each two groups (H=46.09, P<0.01).Intrahepatic NKG2D mRNA expression and NKG2D+ cells density were highest in HBV-ACLF group (6.58±1.86 and 30.69±6.67, respectively), followed by CHB group (3.25±0.95 and 17.36±4.13, respectively) and chronic HBV carriers (0.69±0.20 and 3.16±1.24, respectively), with the statistically significant differences between each two groups (H=52.10 and 52.73 respectively, both P<0.01).The similar patterns were observed in serum IFN-γ, TNF-α, perforin and granzyme B concentrations.Conclusions NKG2D expresses variously in patients with different immune status of chronic HBV infection.Activation of NKG2D may take part in the immune pathogenesis of chronic HBV infection.

Objective To explore the correlation between the efficacy of lamivudine (LAM)therapy and changes of T lymphocyte subsets,CD4+ CD25+ regulatory T lymphocytes (Treg),and levels of interleukin-10 (IL-10)and interferon-gamma (IFN-γ)in the peripheral blood of patients with chronic hepatitis B (CHB).Methods Ninety CHB patients were enrolled in this study.T lymphocyte subsets in the peripheral blood were detected by flow cytometry at baseline and week 52 of LAM therapy.The frequencies of CD4+ CD25+ Treg in the peripheral blood were detected by flow cytometry and levels of IL-10 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA)at baseline,week 12,24,36 and 52.The comparisons of overall means between groups and within groups were done by analysis of variance or Dunnett's test.The comparison of means before and after LAM therapy was done by paired t test.Results In 32 complete-responders of 90 CHB patients,the proportions of CD4+ T lymphocytes,CD8+ T lymphocytes and CD4+/CD8+ ratio were increased significantly after LAM therapy (t=4.055、3.267、2.328,all P＜0.05); the frequencies of CD4+CD25+ Treg at baseline,week 12,24,36 and 52 were (5.40±0.60)%,(4.99±0.59)%,(4.54± 0.72)%,(3.86±0.95)% and (3.44±0.76)%,respectively; the levels of IFN-γ,IFN-γ/IL-10 ratio were increased,while the IL-10 level was decreased after LAM therapy.In 43 partial-responders,the proportion of CD4+T lymphocytes and ratio of CD4+/CD8+ were increased after LAM therapy (t= 3.484,2.018,both P＜0.05); the proportion of CD8+ T lymphocytes was not changed significantly after therapy; the frequencies of CD4+ CD25+ Treg at baseline,week 12,24,36 and 52 were (5.65±0.60)%,(5.23±0.63)%,(4.65±0.98)%,(4.42±0.97)% and (4.32±0.82)%,respectively;IFN-γ level,IFN-γ/IL-10 ratio were increased,while IL-10 level was decreased.In 15 non-responders,the proportion of T lymphocyte subsets,the frequency of CD4+ CD25+ Treg,the levels of IFN-γ and IL-10 were not changed significantly after LAM treatment.Conclusions In CHB patients who have achieved response after LAM therapy,the frequency of CD4+ CD25+ Treg in the peripheral blood is decreased,while ratios of CD4+/CD8+ and IFN-γ/IL-10 in the peripheral blood are increased.

Objective To observe the expressions of interferon gamma (IFN-γ) and IFN-γ-inducible protein 10 (IP-10) at different stages of chronic hepatitis B virus (HBV) infection,and to investigate the relationship between IP-10 with hepatic inflammation activity and hepatitis aggravation.Methods Fifteen chronic hepatitis B (CHB) patients,15 asymptomatic HBV carriers (AsC) and 15 chronic severe hepatitis B (CSHB) patients were enrolled in the study from January 2010 to December 2011 in the Third Hospital of Hebei Medical University.The liver samples were collected by percutaneous needle biopsy or from liver transplantation.The IFN-γ and IP-10 mRNA expressions were measured by quantitative real-time polymerase chain reaction (PCR).Localization and hemi-quantitative analysis of IFN-γand IP-10 proteins were performed by immunohistochemistry staining.Concentrations of serum IFN-γ and IP-10 were quantified by enzyme linked immunosorbent assay (ELISA).HBV markers and liver function were also evaluated for each patient.Results Serum IFN-y and IP-10 concentrations increased significantly in CHB [(415.27±145.52) ng/L and (6.98± 1.12) ng/L,respectively] and CSHB [(658.33 ± 213.52) ng/L and (10.78 ± 1.19) ng/L,respectively] patients compared with AsC [(142.09 ± 47.64) ng/L and (2.4 7 ± 0.60) ng/L,respectively] patients,and were highest in CSHB patients (F=43.48,256.98 ;both P＜0.05).Meanwhile,intrahepatic IFN-γ and IP-10 mRNA and protein expressions paralleled with IFN-γ and IP-10 concentrations in the serum,which was highest in CSHB patients,followed by CHB and AsC patients (F＝693.85,210.21,433.05,214.46; all P＜0.05).Furthermore,Spearman linear correlation analysis showed that serum IP-10 level was positively correlated with both hepatic inflammation activity and serum IFN-γ concentration in CHB and CSHB patients (r =0.76 and r 0.77,respectively;both P ＜ 0.05).Conclusions IP-10,one important immunologic marker of regulating anti HBV activation,indicates progression from immune tolerance phase to immune clearance phase.Furthermore,it may affect the degree of inflammation and hepatitis aggravation.