The aim of the present study was to investigate the effects and possible mechanism of tetramethylpyrazine(TMP)on morphine-induced microglia activation and tolerance. The antinociception and morphine tolerance were assessed in mice using hot-water tail flick test. IBA-1(ionized calcium binding adapter molecule 1), the marker of microglia, was detected by immumofluorescence method. The expression of p-p38 MAPK and total p38 MAPK(mitogen-activated protein kinase, MAPK)was analyzed by Western blot; real-time polymerase chain reaction(RT-PCR)was used to detect the expression level of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β). Results showed that TMP(15, 30, 60 mg/kg, ip)inhibited morphine-induced up-regulation of IBA-1, p-p38, TNF-α and IL-1β in a dose-dependent manner, yet with no effect on the expression of total p38 MAPK. In conclusion, TMP significantly inhibited the activation of microglia evoked by morphine via p38 MAPK signaling pathway, thus attenuating morphine antinociception tolerance.

To investigate the neuroprotective effect and possible mechanism of masitinib on cerebral ischemia-reperfusion injury in rats, healthy adult male Sprague-Dawley rats were divided into sham group (n = 12), model group (n = 12), masitinib low dosage group (n = 12), masitinib middle dosage group (n = 12), and masitinib high dosage group (n = 12). All rats was subjected to middle cerebral artery occlusion (MCAO) for two hours and reperfusion except sham group, and received treatment twice per day for 7 days once reperfusion started.Neurological score, infarct volume, and brain water content were detected; some autophagic markers, apoptotic and inflammatory cytokines were evaluated by Western blot and PCR after 7 d of reperfusion. Treatment with masitinib significantly ameliorated neurologic deficit, infarct volume and brain water after I/R injury. Masitinib also decreased the ratio of LC3II/I and the expression of Beclin-1 and increased the expression of p62 in the brain tissues of rats with I/R injury.Furthermore, it could inhibit apoptosis-related proteins and NF-κB expression. Masitinib could relieve the cerebral ischemia-reperfusion injury in rats through inhibiting autophagy and apoptosis.

Objective To investigate the effect of EP4 gene silencing on the growth and migration of K1 cells. Methods K1 cells with stable knockdown of EP4 were constructed with lentiviral vector. QRT-PCR and western blot analysis were used to detect the expression of EP4 mRNA and protein in K1 cells. CCK8 assay and flow cytometry were employed to measure cell viability and apoptosis. Transwell assay was applied to detect cell migration. Results Compared with the negative control group,the mRNA and protein expression of EP4 were sig-nificantly decreased in K1 cells with stable knockdown of EP4. Furthermore,shRNA-mediated silencing of EP4 gene remarkably suppressed cell viability and induced apoptosis of K1 cells.The migration of K1 cells with knock-down of EP4 was decreased compared with the negative control group. Conclusions EP4 gene silencing can in-hibit growth and induce apoptosis of K1 cells.Downregulation of EP4 can significantly reduce migration of K1 cells.

LC3-associated phagocytosis (LAP) is a special phagocytosis occurring at the intersection of the two pathways of phagocytosis and autophagy. A hallmark event of the LAP process is the recruitment of microtubule-associated proteinⅠlight chain type 3-Ⅱ(LC3Ⅱ) to the phagosome surface of the monolayer membrane structure. The LAP pathway relies on the functions of the RUN domain and cysteine-rich domain containing, Beclin 1-interacting protein (Rubicon) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The LC3-associated phagosome (LAPosome) binds to the lysosome to digest and degrade the contents. In recent years, increasing studies have found that LAP plays an important role in the infections caused by pathogenic microorganisms including fungi and bacteria. LAP is a crucial way in the host to resist and degrade the infection of pathogenic microorganisms. However, some pathogenic microorganisms can effectively escape from LAP in the host and even use LAPosome as a place for colonization and replication. This article summarized the recent progress in the role of LAP in host defense against pathogenic microorganism infection and the significance of it in the occurrence and development of diseases.

Objective To investigate the risk factors of postoperative fecal contamination in children pa-tients with Hirschsprung's disease(HSCR),and to construct and evaluate the risk predictive model.Methods The clinical data in 377 children patients with HSCR in 3 class 3A hospitals in Guangxi from Janu-ary 2016 to June 2021were retrospectively analyzed by adopting the convenience sampling method.The pa-tients were divided into the modeling group(n=264)and testing model group(n=113)with a ratio of 7∶3.The risk factors of postoperative fecal soiling were analyzed by the single factor and multiple factors,and the risk predictive model was constructed.The receiver operating characteristic(ROC)curve was used to detect the discriminative ability of the model and the H-L test was used to determine the goodness of fit of the mod-el.The model was prospectively validated in 21 children patients with HSCR from August to December 2021.Results Among 377 children patients with HSCR,the fecal soiling occurred in 131 cases with a incidence rate of 34.75％.The constructed predictive model of fecal contamination risk after HSCR operation:logit(P)=-2.385+1.697 × special type of megacolon+0.929 × Soave+0.105 × length of bowel resection+2.065 × il-literate caregivers+0.808 × caregivers'implementation of postoperative diet+0.867 × postoperative defecation training by caregivers.The area under the curve(AUC)in the modeling group was 0.849,the Yoden index was 0.53,the optimal critical value of the model was 0.32,the sensitivity was 76.00％,and the specificity was 77.00％.The H-L test,X2=6.649,P=0.575.AUC of the testing model group was 0.736,the sensitivity was 81.25％,and the specificity was 78.46％.The prospective validation results showed that the sensitivity and specificity of the model were 66.67％and 100％respectively.Conclusion The constructed model has good i-dentification and predictive ability.

Objective To test the antimicrobial susceptibility of Staphylococcus aureus from children with impetigo,and to assess the differences in randomly amplified polymorphic DNA profiles between sensitive and resistant Staphylococcus aureus strains.Methods Secretion specimens were obtained from the impetiginous lesions of 178 children,and subjected to bacterial culture.The susceptibility of 162 Staphylococcus aureus isolates against 21 antibiotics was tested.Randomly amplified polymorphic DNA PCR(RAPD-PCR)was performed to characterize the genotype of Staphylococcus aureus.Results Totally,180 bacterial strains were isolated from 178 children with impetigo in Chengdu,including 162(90.00％)Staphylococcus aureus strains.Of the 162 Staphylococcus aureus strains,148 were methicillin sensitive Staphylococcus aureus(MSSA),14 methicillin resistant Staphylococcus aureus(MRSA).The most active antibiotic was minocycline,followed by teicoplanin,quinupristin,vancomycin and nitrofurantoin,while the resistance rate to penicillin was highest,followed by that to erythromycin,clindamycin,compound sulfamethoxazole and tetracycline.All the Staphylococcus aureus isolates were sensitive to fusidic acid,nitrofurantoin,vancomycin,minocycline and teicoplanin.According to RAPD-PCR,the 162 Staphylococcus aureus strains were divided into 8 genotypes,with the three most prevalent genotypes being Ⅲ(31.48％),Ⅱ(26.54％)and Ⅵ(25.93％),which accounted for 65.43％(106/162)in all the strains.The 148 MSSA strains fell into 8 genotypes,with genotype Ⅲ(50 strains,33.78％),Ⅵ(39 strains,26.35％)and Ⅱ(33 strains,22.30％)being the most prevalent genotypes;the 14 MRSA strains fell into 3 genotypes,i.e.,genotype Ⅱ(10 strains,71.43％),Ⅵ(3 strains,21.43％),and Ⅲ(1 strain,7.14％).Conclusions Staphylococcus aureus is the most prevalent pathogenic bacteria in children with impetigo in Chengdu area,which is highly sensitive to minocycline,teicoplanin and quinupristin,and falls into 8 genotypes according to RAPD-PCR with genotype Ⅲ being the most common genotype.

OBJECTIVETo evaluate the association between the two single nucleotide polymorphisms located in catechol-O-methyltransferase (COMT) gene and type 2 diabetes mellitus (T2DM)in Han population in Guangdong province.

METHODSTwo tagSNPs (rs4646312 and rs4680) were picked out from COMT gene. Using the SNPscan(TM) Kit, SNP genotyping was then performed, in two cohorts, including 595 cases and 725 controls. Finally, Chi-square test, logistic regression model and other methods were employed for statistical analysis.

RESULTSThe frequencies of TT, CT and CC of rs4646312 appeared to be 304(51.1%), 234(39.3%)and 57 (8.6%) in cases, 323 (44.6%), 319 (44.0%) and 83(11.4%)in controls, respectively. The frequencies of GG,GA and AA of rs4680 were 311(52.4%), 236 (39.8%) and 46(7.8%)in cases, 417(57.7%), 265 (36.6%) and 41 (5.7%) in controls, respectively.

RESULTSshowed that SNP rs4646312 was significantly associated with T2DM both in allelic association analysis (P = 0.020,OR = 1.26, 95%CI:1.04-1.53)and in recessive model (P = 0.022, OR = 1.35, 95% CI:1.05-1.74)after adjustment for sex,BMI and TG. The association between rs4680 and T2DM was not significant, but BMI was remarkably different among the three genotypes of rs4680 after controlling for other factors.

CONCLUSIONSNP rs4646312 of COMT gene was associated with the increased risk of T2DM in Han population in Guangdong province. However, rs4680 was not significantly associated with T2DM.

Adult ; Aged ; Alleles ; Case-Control Studies ; Catechol O-Methyltransferase ; genetics ; Diabetes Mellitus, Type 2 ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

BACKGROUND: The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion. METHODS: The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software. RESULTS: A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group. CONCLUSIONS Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.
Antineoplastic Agents ; adverse effects ; therapeutic use ; Cisplatin ; adverse effects ; therapeutic use ; Cyclobutanes ; adverse effects ; therapeutic use ; Humans ; Organoplatinum Compounds ; adverse effects ; therapeutic use ; Pleural Effusion, Malignant ; drug therapy ; Randomized Controlled Trials as Topic