ObjectiveTo clarify whether epigallocatechin gallate （EGCG） is involved in the clearance of amyloid β-protein （Aβ） and autophagy induction by microglia， so as to explore the potential mechanisms of EGCG in the prevention and treatment of Alzheimer's disease （AD）. MethodsSix-month-old APP/PS1 mice were randomly divided into model and EGCG groups， with some additional wild type （WT） mice as the control group， each group consisting of 15 mice. The EGCG group received continuous gavage administration［5 mg/（kg·d）］ for 8 weeks， followed by the open field test and Y-maze to assess the learning and memory abilities of the mice. Thioflavin-S staining was used to evaluate the content and distribution of amyloid β-protein （Aβ）in the brain parenchyma of the mice， and immunofluorescence was employed to detect the expression levels of Aβ_1-42， glial fibrillary acidic protein （GFAP）， and ionized calcium-binding adapter molecule 1 （Iba1） in the hippocampal tissue of the mice. Additionally， N9 mouse microglial cells were induced with 20 µmol/L Aβ_1-42， and the cell viability was measured after treatment with different concentrations of EGCG （5 µmol/L， 10 µmol/L， 20 µmol/L）. Western blotting was used to detect the levels of Aβ_1-42， low density lipoprotein receptor-related protein 1（LRP1）， receptor for advanced glycation endproducts （RAGE）， amyloid precursor protein （APP）， insulin degrading enzyme （IDE）， neprilysin （NEP）， microtubule associated protein 1 hydrogen chain 3（LC3）-Ⅱ/LC3-Ⅰ， phosphatidylinositol 3-hydroxy kinase（PI3K）， p-PI3K， protein kinase B （AKT）， p-AKT， mammalian target of rapamycin （mTOR）， p-mTOR， and histone deacetylase 6（HDAC6）. Finally， through the co-culture of microglial cells and neuronal SH-SY5Y cells， cell viability and Caspase-3 levels were measured to verify the protective effect of EGCG-mediated Aβ clearance on neurons. ResultsEGCG increased the activity time and frequency of APP/PS1 mice in the central area of the open field （P<0.05）， and enhanced the percentage of alternation in the Y-maze test （P<0.01）； EGCG reduced Aβ deposition in the hippocampal tissue of APP/PS1 mice and increased the number of microglia； in vitro experiments showed that EGCG improved the survival rate of Aβ-induced N9 cells （P<0.01）， upregulated RAGE activity （P<0.05）， and promoted the internalization and phagocytosis of Aβ （P<0.01）. ECGC activated microglial autophagy by downregulating the level of HDAC6 （P<0.05）， inhibiting the phosphorylation of PI3K， AKT， mTOR （P<0.001）， and increasing the LC3-Ⅱ/LC3-I ratio （P<0.001）； EGCG improved the survival rate of SH-SY5Y cells （P<0.05） and reduced the activity of Caspase-3 （P<0.01） by clearing Aβ_1-42 through microglia， and had a protective effect on neurons. ConclusionEGCG activates microglial autophagy to clear Aβ by targeting and inhibiting the HDAC6-PI3K/AKT/mTOR axis.

Objective To analyze pathogen distribution and drug resistance in a tertiary hospital in Shenyang in 2022 and provide evi-dence-based guidance for this and other hospitals to formulate antibacterial drug application strategies.Methods In 2022,bacterial iso-lates collected from patients in a tertiary hospital in Shenyang were identified and subjected to drug sensitivity tests based on the require-ments of the national clinical laboratory operation procedures.The data were analyzed using Whonet 5.6 software.Results In total,4968 pathogenic strains were isolated from this hospital in 2022.The top five isolates were Escherichia coli,Klebsiella pneumoniae,Acineto-bacter baumannii,Enterococcus faecalis,and Pseudomonas aeruginosa.The resistance rates of Escherichia coliand Klebsiella pneumo-niaeto carbapenems were 1.9%and 17.7%,respectively.The resistance rates of Enterobacter cloacaeto imipenem and meropenem were 26.7%and 25.0%,respectively.The isolation rate of methicillin-resistant Staphylococcus aureus(MRSA)was 15.6%.The resistance rates of vancomycin-resistant Enterococcusand linezolid-resistant Enterococcus faecaliswere 7.1%and 11.6%,respectively.The resist-ance rates of tropical yeasts to fluconazole was>20%.Conclusion The distribution and drug resistance of pathogens in this hospital differed from those in other regions of China.The drug resistance of strains in this hospital should be closely monitored to understand the distribution and drug resistance of pathogens in a timely manner and to provide guidance for the diagnosis and treatment of infections.

Objective To observe the clinical efficacy of ebastine combined with Runzao Zhiyang capsules in the treatment of patients with chronic urticaria. Methods A total of 126 patients with chronic urticaria admitted to Department of Dermatology of Tianjin Third Central Hospital from January 2015 to May 2017 were enrolled and they were divided into two groups by the random number table method. The patients in control group (62 cases) were given oral ebastine administration 10 mg once per day, and those in observation group (64 cases) received oral administration of ebastine 10 mg once per day combined with Runzao Zhiyang capsule 2 g, 3 times per day, the therapeutic course being 4 weeks. The changes of clinical efficacy and the symptom scores, including urticaria activity score (UAS) and dermatolo-gical disease life quality index (DLQI) scores of the two groups were observed after treatment of 4 weeks;the incidence of adverse reactions and the recurrence situation after drug withdrawal for 4 weeks at follow-up were analyzed. Results Compared with the control group, the total effective rate of the observation group was significantly increased [92.2% (59/64) vs. 79.0% (49/62), P ＜ 0.05]. After treatment, the overall UAS score and DLQI score in two groups were both significantly decreased, the degree of decrease in observation group were more siginificant than those in control group [UAS: 1.26 (0.52 - 7.35) vs. 1.68 (0.75 - 8.65), DLQI: 0.56±0.52 vs. 1.57±0.96, P ＜ 0.01]. In addition, the total decrease degree of symptom score reducing index (SSRI) in the observation group was significantly greater than that in the control group [(76±21)% vs. (69±23)%, P ＜ 0.05], the incidence of adverse reactions [7.8% (5/64) vs. 12.8% (8/62)] and recurrence rate [8.3% (3/64) vs. 23.8% (5/62)] in the observation group were obviously lower than those in the control group (both P ＜ 0.05). Conclusion The efficacy of ebastine combined with Runzao Zhiyang capsule in the treatment of patients with chronic urticaria is prominent and superior to that of using ebastine alone, the combined method is capable of elevating the therapeutic effect obviously and has less adverse reactions.

Objective To analyze the clinical data of brucellosis,and to provide references for brucellosis therapy.Methods The patients definitely diagnosed brucellosis at the First Affiliated Hospital of Zhengzhou University from January 2013 to June 2016 were assessed,data of clinical features,laboratory examination,treatment and prognosis were analyzed.Results Of all 99 cases,the mean age was (46.7 ± 15.7) years old,83 cases had a history of closely contacted with sheep,2 cases with pig and 1 case with cattle.The occupational distribution of patients included 90 farmers,1 veterinarian,2 cooks,6 children and students.All patients had clinical manifestations such as fever,fatigue,and sweating.There were 18 patients with back and joint pain,13 cases had abnormal manifestation on magnetic resonance imaging (MRI).Blood culture was positive in 54 (71.05％,54/76) and serum test tube agglutination test was positive in 61 (98.39％,61/62).Eighty-one patients received doxycycline combined with rifampicin treatment,six months laters,all patients were cured.Conclusions Sheep are the main sources of infection for brucellosis.Fatigue,sweaty and fever are the most common symptoms,and osteoarticular is the most frequently involved.Serum agglutination test and blood culture are important tests for diagnosis of brucellosis.Doxycycline combined with rifampicin was the most common used antibiotics regimen.Early,combined,regular,full-course antibiotic treatment has a better prognosis.

ObjectiveTo investigate the inhibitory effect of fibroblast growth factor-21 (FGF-21) on the carcinogenesis of L02 cells induced by diethylnitrosamine (DEN).Methods L02 cells were cultured and treated with different concentrations of DEN (1,10,20,50,100,and 150 μmol/L).MTT assay was used to measure the influence of DEN on the viability of L02 cells,and an appropriate stimulation concentration of DEN (20 μmol/L) was selected for further study.The malondialdehyde (MDA) and superoxide dismutase (SOD) detection kits were used to measure the levels of MDA and SOD in L02 cells treated by DEN (20μmol/L) and normal L02 cells.Then L02 cells were divided into model control group (treated with 20μmol/L DEN and PBS),low-dose FGF-21 group (20 μmol/L DEN + 1 μmol/L FGF-21),and high-dose FGF-21 group (20 μmol/L DEN +2 μmol/L FGF-21).The levels of MDA and SOD were measured after 12 hours of cell culture.Real-time PCR and Western blot were used to measure the expression of βKlotho (KLB),and Western blot was used to measure the level of phosphorylated protein kinase B (p-AKT).The t-test was used for comparison of continuous data between two groups;an analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results There was a significant increase in the level of MDA and a significant reduction in the level of SOD after L02 cells were treated with DEN (t =9.336 and 16.281,P =0.011 and 0.004).Compared with the model control group,the low-and high-dose FGF-21 groups had a significant reduction in the level of MDA and a significant increase in the level of SOD (P ＜ 0.05),and compared with the low-dose FGF-21 group,the high-dose FGF-21 group had a significantly lower level of MDA and a significantly higher level of SOD (P =0.030 and 0.042),and there was a significant difference between two groups.The high-and low-dose FGF-21 groups had significantly higher mRNA expression of KLB than the model control group (P ＜ 0.001),and the high-dose FGF-21 group had significantly higher mRNA expression of KLB than the low-dose FGF-21 group (P ＜ 0.001),and there was a significant difference between two groups;the protein expression of KLB showed the same trend.The model control group had a significantly higher level of p-AKT than the other two groups (P ＜0.05),and the high-dose FGF-21 group had a significantly lower level of p-AKT than the low-dose FGF-21 group (P ＜ 0.05).Conclusion DEN can increase oxidative stress in L02 cells.By upregulating the expression of KLB,FGF-21 can reduce the level of p-AKT,inhibit oxidative stress in L02 cells induced by DEN,and thus inhibit the development of hepatocellular carcinoma.

Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.

OBJECTIVE:To observe the short-term efficacy and ADR of tenofovir disoproxil fumarate(TDF)in the treatment of multi-drug resistant chronic hepatitis B(CHB). METHODS:32 patients with multi-drug resistant CHB were analyzed retrospec-tively,and HBV drug-resistant genes were detected before treatment;there were a number of points to resistance;they were gave TDF orally. The recovery rate of serum alanine aminotransferase(ALT),HBV-DNA conversion rate,lactic acid and renal function were observed before and after treatment. RESULTS:The recovery rate of ALT reached 100% at 3 months,and the conversion rate of HBV-DNA reached 96.88%. The lactic acid levels and renal dysfunction was not found during treatment. CONCLUSIONS:TDF take effect quickly on multi-drug resistant CHB,and no obvious ADR is found.

OBJECTIVETo perform a retrospective cohort study in order to determine the differences in short-term curative effect of ribavirin in combination with interferon alfa (IFNa)-2a vs. pegylated (Peg)-IFNa-2a in patients with chronic hepatitis C (CHC).

METHODSOne-hundred-and-eighty-eight treatment of the CHC patients who were administered combination therapy of ribavirin with IFNa from 2010 to 2012. One-hundred-and-thirty-three of the patients received the therapy with IFNa-2a and the remaining 55 received Peg-IFNa-2a. Hepatitis C virus (HCV) load and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at treatment weeks 4, 12, 24, and 48. Adverse reactions were recorded. Differences between the groups were assessed by statistical analysis.

RESULTSThe patients in the Peg-IFNa-2a group and the IFNa-2a group showed no significant difference in sex distribution, age, smoking habits, or drinking habits at baseline (all P more than 0.05). Both antiviral therapies significantly reduced the HCV load and levels of ALT and AST (baseline levels vs. all treatment weeks examined, P less than 0.05); however, the reduction in the HCV load at week 4 was significantly more robust with the Peg-IFNa-2a therapy (2.96 ± 0.66) log10 IU/ ml vs. (3.47 ± 1.42)1og10 IU/ml; F =4.14, P=0.04). The Peg-IFNa-2a group also showed a significant higher rate of rapid virological response (RVR) than the IFNa-2a group (72.72% vs .57.14%; x²=4.37, P=0.04), but there were no statistically significant differences found between the two groups for early virological response rate (EVR), endpoint antiviral treatment virologic response rate (ETR), biochemical response rate, or rate of adverse reactions (all P more than 0.05).

CONCLUSIONRibavirin in combination with Peg-IFNa-2a produces a better RVR than in combination with IFNa-2a .Yet, the EVR, ETR, biochemical response rate, and rate of adverse reactions is similar for the two forms of IFNa-2a. Further studies are required to determine the potential superiority of Peg-IFNa-2a for a long-term curative effect.

Adolescent ; Adult ; Aged ; Antiviral Agents ; therapeutic use ; Child ; Child, Preschool ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; therapeutic use ; Retrospective Studies ; Ribavirin ; therapeutic use ; Treatment Outcome ; Young Adult

Objective To design technique of local flap transposition to refine the aesthetic appearance of reconstructed fingers by toes transfer.Methods Nine cases with 21 reconstructed finger were included,which involved 6 males and 3 females with an average age of 21.8 years(range,18-34years).A lingual contour flap with a lateral pedicle Was shifted from the inflated distal pulp to the narrow middle part of the"finger"to refine the aesthetic appearance.Overall results were evaluated in terms of the survival of the flap,the appearance improvement and the functional influence of the reconstructed finger.Results All of the flaps survived and healed perfectly.After a mean follow-up of 9.3 months(range,6-12months),the appearance of the reconstructed fingers were impmved apparently.There was little influence on the function of the finger.The results showed that all the patients gained more acceptable fingers.Conclusion From our experience,local flap transposition is a useful method for remolding of reconstructed fingers by toes transfer.