Search

Yan Zhang,1 Li-Hua Hu,2,* Jia Huang,2 Ming-Qin Lu,2 Fan-Rong Zeng,2 Shao-Chun Chen1,3,* 1School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China; 2Zhejiang Provincial Institute of Dermatology, Deqing, People’s Republic of China; 3National Center for Sexually Transmitted Diseases Control, Chinese Center for Disease Control and Prevention, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Hua Hu, Email dqhlhua@163.com Shao-Chun Chen, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of China, Email chensc@ncstdlc.orgObjective: This study aimed to assess the drug susceptibility of clinical isolates of Neisseria gonorrhoeae to spectinomycin, ceftriaxone and azithromycin. Moreover, the temporal trends in the minimum inhibitory concentration (MIC) of five antibiotics from Zhejiang, China, are also in the scope of this study.Methods: A total of 1710 gonococcal clinical strains were collected between 2007 and 2021 from health-care institutions in Zhejiang. The MICs of ceftriaxone, azithromycin, spectinomycin, penicillin and ciprofloxacin were assessed by agar dilution method on 1710 Neisseria gonorrhoeae isolates. Count data were expressed as strains and rates, and MICs distribution was elucidated using descriptive statistics.Results: The total resistance rates of gonococci to azithromycin, spectinomycin, penicillin and ciprofloxacin in this study were 19.3%, 0.3%, 75.4% and 99.7%, respectively.Conclusion: The in vitro results showed a high prevalence of resistance to ciprofloxacin and penicillin. Azithromycin resistance rate has exceeded 5%, suggested a high prevalence of resistance. Ceftriaxone and spectinomycin are suggested based on this study for the treatment of Neisseria gonorrhoeae in Zhejiang.Keywords: Neisseria gonorrhoeae, agar dilution method, ceftriaxone, spectinomycin

Objective:To investigate liver histologic disease in chronic hepatitis B (CHB) patients with normal ALT (Methods:We retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtain their 1-year follow up data to establish a predict model of 1-year HBVDNA clearance rate through Logistic regression. Results:The proportion of patient with significant histological disease (significant liver necroinflammation or fibrosis) in the high nALT group was significantly higher than that in the low nALT group (56.43% vs 43.82%, p < 0.001, Table 1). HbeAg negative, GGT and ALT value (OR 0.024, 95% CI 0.011–0.055, p < 0.001; OR 1.027, 95% CI 1.006–1.050, p = 0.013; OR 1.993,95% CI 1.115–3.560, p = 0.020, Table 4) were independent predict factors. High normal ALT is an indicator of 1-year HBVDNA clearance after antiviral treatment. Conclusion: CHB patients with high-normal ALT have significantly higher histological disease rates, and these patients may benefit better from antiviral therapy. We suggest should undergo histological evaluation of liver disease as soon as possible. We also propose these patients should be offered antiviral therapy when feasible.

Sepsis refers to the body's dysfunctional response to infection and leads to life-threatening organ dysfunction. Dentritic cells (DCs), a kind of powerful functional antigen-presenting cell, plays a critical role in immune response and has been used in the field of immunotherapy for multiple diseases. Endotoxin tolerance is a phenomenon that believed to prevent the organism from producing persistent and excessive inflammatory reaction and numerous studies indicated that endotoxin tolerant dendritic cells (ETDCs) have therapeutic effects on experimental models of several diseases. MicroRNA155(miR155), which plays a pivotal role in various physiological and pathological processes in immunity, was reported associated with the formation of endotoxin tolerance. In this paper, we explored the change of properties after silencing miR155 in ETDCs then attempted to study its effects on the murine model of sepsis. Endotoxin tolerant dendritic cells were transfected with adenovirus silencing miR155 and negative control adenovirus, thereafter collected for reverse transcription polymerase chain reaction of miR155, costimulatory molecules analysis, allogeneic mixed lymphocyte reaction and cytokine concentration evaluation. 42 balb/c mice were randomly divided into control group, sham operation group, sepsis group, ETDCs treatment group and miR155-/-ETDCs treatment group. Two treatment groups respectively received tail vein injection of ETDCs and miR155-/-ETDCs 24h earlier than cacal ligation puncture. Our results revealed that silencing miR155 could deepen the immature status of ETDCs and both ETDCs and miR155-/-ETDCs performed a protective effect in murine sepsis models while miR155-/-ETDCs got a better protection. We reasoned that miR155 participates the formation of endotoxin tolerance and the protective effects of ETDCs and miR155-/-ETDCs in the early stage of sepsis may achieved by altering the concentration of mouse cytokines to affect T cell differentiation and exert negative immune regulation.

To explore the mechanism of endotoxin tolerance(ETT) through observing the gene expression of SOCS1 and SOCS3 in the livers of ETT rats.SD male rats were divided randomly into acute liver failure model group (ALF group) and ETT group. LPS 0.1 mg/kg (ETT group) or normal saline (ALF group) was administered five consecutive intraperitoneal injections at 24 h intervals, then, the two groups were treated with intraperitoneal injection of D-GalN 800 mg/Kg and LPS 8 microg/rat 24 h later. Liver histopathology and fine structure of rats were observed by HE staining and electron microscope. The TNF-alpha level were estimated by ELISA, the concentrations of endotoxin were determined by tachypleus amebocyte lysate and the gene expressions of SOCS1 and SOCS3 in the liver were measured by RT-PCR at 0, 2, 6, 12, 24 and 48 h after the injection of D-GalN/LPS.D-GalN/LPS induced acute liver injury was attenuated significantly in ETT group. The concentrations of endotoxin and the TNF-alpha level were evidently lower in the ETT group than those in the ALF group (endotoxin: 6 h: 1.11 +/- 0.38 vs 0.74 +/- 0.22, 24 h: 1.12 +/- 0.24 vs 0.86 +/- 0.21, all P0.05, 12 h: 1.88 +/- 0.35 vs 0.62 +/- 0.16, 48 h: 1.10 +/- 0.13 vs 0.84 +/- 0.19, all P0.01; TNF-alpha: 6 h: 86.9 +/- 12.6 vs 70.0 +/- 12.8, P0.05, 12 h: 77.0 +/- 18.1 vs 48.8 +/- 12.8, 24 h: 63.8 +/- 9.2 vs 39.1 +/- 5.7, 48 h: 53.2 +/- 8.3 vs 38.2 +/- 9.9, all P0.01). In the ALF group, the expressions of SOCS-1 and SOCS-3 were obviously higher than those in the controls and reached peak at 12th hours and 6th hours respectively. The gene expression of SOCS1 and SOCS3 in the liver in ETT group were increased significantly and much higher than those in ALF groups. (SOCS1: 6 h: 0.955 +/- 0.186 vs 1.349 +/- 0.390, 48 h: 0.766 +/- 0.145 vs 0.970 +/- 0.205, all P0.05, 2 h: 0.554 +/- 0.164 vs 0.841 +/- 0.175, 12 h: 1.130 +/- 0.181 vs 1.888 +/- 0.573, 24 h: 0.990 +/- 0.212 vs 1.550 +/- 0.439, all P0.01; SOCS3: 6 h: 0.914 +/- 0.054 vs 1.039 +/- 0.109, 12 h: 0.781 +/- 0.044 vs 0.863 +/- 0.063, all P0.05, 2 h: 0.681 +/- 0.139 vs 0.898 +/- 0.058, 24 h: 0.700 +/- 0.065 vs 0.811 +/- 0.055, all P0.01).LPS pretreatment can induce endotoxin tolerance of rats, inhibited the level of TNF-alpha and endotoxin. The up-regulation of SOCS1 and SOCS3 gene expression may be one of the possible mechanisms responsible for endotoxin tolerance.

To study the changes of plasma cytokines in patients with severe hepatitis treated with a probiotic preparation.One hundred twelve patients with severe hepatitis treated with a basic regimen were randomly divided into a probiotic preparation treatment group and a control group. Their plasma cytokines such as tumor necrosis factor alpha, interleukin-2, interleukin-6, interleukin-10, were determined by conventional techniques.Clinical symptoms of 84.5% of the treatment group were obviously improved. The treatment effectiveness in this group was better than that in the control group (X2=8.888). It showed that liver functions were significantly improved compared to those of the control group . After the probiotic preparation therapy, there were significant decreases in the concentrations of TNFa and IL-6. TNFa and IL-6 in the treatment group and in the control group were (109.4+/-14.7) pg/ml vs (128.7+/-18.8) pg/ml and (84.3+/-20.1) pg/ml vs (109.1+/-18.7) pg/ml respectively. However, the concentrations of IL-10 and IL-2 in the treatment group increased obviously: IL-2 was (59.8+/-12.2) pg/ml vs (47.1+/-6.7) pg/ml and IL-10 was (30.6+/-6.6) pg/ml vs (22.5+/-6.1) pg/ml.The probiotic preparation treatment effectively reduces the TNFa and IL-6 and increases the concentrations of IL-10 and IL-2 in the blood of the patients with severe hepatitis.