Microglia are the inherent macrophages and immune surveillance cells in the central nervous system (CNS) and compose the first guard of immune defense in CNS .The activation of microglia is one of the pathological features of many CNS diseases and acts as an important role during the multiple sclerosis (MS) process.MS is a CNS disease characterized by neuroinflammatory infiltration , demyelination and axonal damage.Accumulation of activated microglia at the injury site has been observed in brains of MS patients and experimental animals with complicated mechanisms.Microglia have both detrimental and beneficial roles .For instance, microglia have been shown to recruit and reactivate T cells in the CNS and release many detrimental molecules such as proteases , inflammatory cytokines, and free radicals.Conversely, they have also been observed to aid in axonal regeneration and remyelination as well as assist in the clearance of inhibitory myelin debris .In addition, microglia have been shown to release a variety of neurotrophic factors . Cuprizone [oxalic acid bis (cyclohexylidene hydrazide )] is a well-known copper-chelating agent.Cuprizone ingestion in mice induces a highly reproducible demyelination of distinct brain regions .Discussion on the detrimental and beneficial aspects of microglia in cuprizone animal models will serve to better understand the development of MS and find out new therapeutic targets.This review will further our understanding of the dichotomous roles of microglia in cuprizone -induced demyelination in animal models of multiple sclerosis .

Objective:To investigate the clinical efficacy and safety of gabapentin or topiramate combined with venlafaxine in the treatment of chronic migraine patients with generalized anxiety disorder.Methods:From June 2018 to February 2020, 127 patients with chronic migraine complicated with generalized anxiety disorder in the Second Affiliated Hospital of Guangxi Medical University were selected. The patients were divided into gabapentin combined with venlafaxine group (observation group, 64 cases) and topiramate combined with venlafaxine group (control group, 63 cases) according to the random number table method, and all patients were treated for 6 months. The headache attack days per month, headache visual analogue scale (VAS), migraine specific quality of life questionnaire V2.1 (MSQ V2.1), headache impact measurement-6 (HIT-6) score, Pittsburgh sleep quality index (PSQI) score were recorded before treatment and 3 and 6 months after treatment.Results:In observation group, 57 cases completed 3 months of treatment, and 53 cases completed 6 months of treatment. In the control group, 56 cases completed 3 months of treatment, and 50 cases completed 6 months of treatment. The headache attack days per month, headache VAS, HIT-6 and PSQI 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (16.31 ± 5.02) and (15.69 ± 6.31) d vs. (22.62 ± 3.27) d, (3.67 ± 1.60) and (1.91±1.05) scores vs. (5.09 ± 1.43) scores, (49.34 ± 11.01) and (47.34 ± 9.05) scores vs. (60.25 ± 11.61) scores, (10.09 ± 2.81) and (9.68 ± 2.74) scores vs. (13.50 ± 2.81) scores; control group: (14.58 ± 7.37) and (9.92 ± 5.07) d vs. (23.05 ± 5.24) d, (4.74 ± 1.15) and (3.16 ± 1.60) scores vs. (5.90 ± 2.06) scores, (42.77 ± 8.02) and (40.09 ± 9.72) scores vs. (59.37 ± 9.08) scores, (9.66 ± 2.71) and (8.62 ± 2.07) scores vs. (14.61 ± 2.79) scores, and there were statistical differences ( P<0.05). The headache VAS 3 and 6 months after treatment in observation group was significantly lower than that in control group, and there was statistical difference ( P<0.05). The functional limitations, function loss, emotional function scores and total score of MSQ V2.1 3 and 6 months after treatment in 2 groups were significantly lower than those before treatment, observation group: (17.62 ± 9.81) and (16.01 ± 5.73) scores vs. (36.96 ± 9.55) scores, (12.17 ± 5.60) and (11.09 ± 3.27) scores vs. (17.06 ± 6.08) scores, (8.42 ± 2.17) and (8.94 ± 1.90) scores vs. (11.40 ± 4.09) scores, (33.24 ± 9.61) and (28.62 ± 5.04) scores vs. (62.75 ± 14.02) scores; control group: (17.08 ± 8.73) and (16.79 ± 5.19) scores vs. (36.82 ± 9.68) scores, (9.04 ± 4.48) and (8.90 ± 3.46) scores vs. (17.26 ±6.01) scores, (6.92 ± 2.61) and (5.15 ± 1.74) scores vs. (11.30 ± 5.47) scores, (31.65 ± 9.17) and (30.66 ± 6.04) scores vs. (62.91 ± 11.18) scores, and there were statistical differences ( P<0.05). There was no significant difference in the effective rate and the incidence of adverse drug reactions 3 and 6 months after treatment between 2 groups ( P>0.05). Conclusions:Gabapentin or topiramate combined with venlafaxine can reduce the degree of headache in chronic migraine patients with generalized anxiety disorder, reduce the number of headache days per month, improve sleep and improve the quality of life. However, the adverse reactions of gabapentin still need to be paid more attention.

Abstract: Objective To establish a rapid detection assay based on fluorescence recombinase polymerase amplification (RPA) targeting Necator americanus eggs, and to evaluate its efficacy, providing technical support for rapid detection of Necator americanus in fecal samples. Methods The fluorescence RPA primers and probe were designed based on the cox1 gene of Necator americanus and then screened the optimal combination to develop the assay. The genomic DNA of Necator americanus eggs was diluted to 7 concentration gradients including 100 pg/µL, 10 pg/µL, 1 pg/µL, 100 fg/µL, 10 fg/µL, 1 fg/µL, 0.1 fg/µL, to determine the detection limit of the assay. The specificity of the assay was demonstrated by detected genomic DNA from Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis and Fasciola hepatica. A total of 44 fecal samples were collected and DNA extraction was performed, and the modified Kato-Katz method, semi-nest PCR method, and fluorescent RPA method were simultaneously used for detection to evaluate the sensitivity and specificity. Results The established fluorescence RPA assay can specifically amplify a fragment of 194 bp of the Necator americanus cox1 gene within 20 min, with a detection limit of 10 fg/µL. There was no cross-reactivity with Schistosoma japonicum, Ascaris lumbricoides, Clonorchis sinensis, Fasciola hepatica after specificity validation. In 44 fecal samples, 27 positive samples were detected by the fluorescence RPA assay, and 26 positive samples were detected by both the Kato-Katz and the semi-nested PCR. The fluorescence curve of sample number 1 was slightly higher than the negative control in the later stage of the reaction, but did not show a similar trend to the positive control, and was therefore judged to be a suspected negative sample. Compared with the Kato-Katz method and the semi-nest PCR method, The sensitivity of the fluorescent RPA method were 100.00% and the specificity were 94.44%, and the consistency of the detection results was good (Kappa=0.953>0.75). Conclusions The assay based on the fluorescence RPA is an efficient, sensitive and specific technique for detecting Necator americanus and it can be applied for surveillance and early warning of hookworm infection.

Abstract: Objective To establish a sensitive and specific nucleic acid detection method for Schistosoma japonicum based on loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) technology. Methods The LAMP primers, gRNA and ssDNA probe that target Schistosoma japonicum SjR2 genes were designed according to the principles of LAMP and CRISPR. The LAMP-CRISPR reaction system was established and optimized. The sensitivity and specificity of the method were evaluated against the ten-fold serial dilutions of plasmid containing SjR2 target sequences, as well as genomic DNA at different stages of Schistosoma japonicum and other parasites, including Fasciola hepatica, Schistosoma mansoni, Taenia saginata, Clonorchis sinensis, Ascaris lumbricoides, Necator americanus, Paragonimus westermani, and Echinococcus granulosus. Additionally, 15 schistosome-infected snail and 30 uninfected samples were tested by LAMP-CRISPR and LAMP methods, respectively, to evaluate the potential of this method for screening for infected snails. Results　The developed LAMP-CRISPR method was able to specifically amplify and detect the SjR2 gene of S. japonicum. The optimal reaction temperature was 37 ℃, and the optimal reaction concentrations were both 40 nmol/L for gRNA and Cas12a protein. No cross-reaction was observed with genomic DNA from other parasites such as F. hepatica. The detection limit of the method was 10 copies/μL when testing 10-fold dilutions of recombinant plasmids as a template. Furthermore, the LAMP-CRISPR method was able to accurately detect genomic DNA from S. japonicum at various stages of development, including eggs, cercariae, schistosomula, juvenile worms, and adult worms. The results of testing 45 snail samples showed no significant difference between the LAMP-CRISPR and LAMP methods for detecting infected snails (χ2=0.05, P>0.05). The sensitivity and specificity of the LAMP-CRISPR method were 100.00% (15/15) and 96.67% (29/30), respectively, compared to the gold standard, while the sensitivity and specificity of the LAMP method were 100.00% (15/15) and 93.33% (28/30), respectively. Conclusions　This established LAMP-CRISPR detection method presented good sensitivity, specificity and reliability, making it a promising tool for rapid detection and risk monitoring of S. japonicum.

Objective:To evaluate the value of preoperative prediction of vessel invasion (VI) of locally advanced gastric cancer by machine learning model based on the venous phase enhanced CT radiomics features.Methods:A retrospective analysis of 296 patients with locally advanced gastric cancer confirmed by pathology in the First Affiliated Hospital of Zhengzhou University from July 2011 to December 2020 was performed. The patients were divided into VI positive group ( n=213) and VI negative group ( n=83) based on pathological results. The data were divided into training set ( n=207) and test set ( n=89) according to the ratio of 7∶3 with stratification sampling. The clinical characteristics of patients were recorded, and the independent risk factors of gastric cancer VI were screened by multivariate logistic regression. Pyradiomics software was used to extract radiomic features from the venous phase enhanced CT images, and the minimum absolute shrinkage and selection algorithm (LASSO) was used to screen the features, obtain the optimal feature subset, and establish the radiomics signature. Four machine learning algorithms, including extreme gradient boosting (XGBoost), logistic, naive Bayes (GNB), and support vector machine (SVM) models, were used to build prediction models for the radiomics signature and the screened clinical independent risk factors. The efficacy of the model in predicting gastric cancer VI was evaluated by the receiver operating characteristic curve. Results:The degree of differentiation (OR=13.651, 95%CI 7.265-25.650, P=0.003), Lauren′s classification (OR=1.349, 95%CI 1.011-1.799, P=0.042) and CA199 (OR=1.796, 95%CI 1.406-2.186, P=0.044) were independent risk factors for predicting the VI of locally advanced gastric cancer. Based on the venous phase enhanced CT images, 864 quantitative features were extracted, and 18 best constructed radiomics signature were selected by LASSO. In the training set, the area under the curve (AUC) of XGBoost, logistic, GNB and SVM models for predicting gastric cancer VI were 0.914 (95%CI 0.875-0.953), 0.897 (95%CI 0.853-0.940), 0.880 (95%CI 0.832-0.928) and 0.814 (95%CI 0.755-0.873), respectively, and in the test set were 0.870 (95%CI 0.769-0.971), 0.877 (95%CI 0.788-0.964), 0.859 (95%CI 0.755-0.961) and 0.773 (95%CI 0.647-0.898). The logistic model had the largest AUC in the test set. Conclusions:The machine learning model based on the venous phase enhanced CT radiomics features has high efficacy in predicting the VI of locally advanced gastric cancer before the operation, and the logistic model demonstrates the best diagnostic efficacy.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.