Objective:To observe the anti-inflammatory and glycometabolic effects of glutathione(GSH)on macrophages in collagen induced arthritis(CIA)mice.Methods:①CIA model establishment and groups:A total of 14 female DBA/1J mice were ran-domly divided into:CIA+PBS group and CIA+GSH group.The mice were sacrificed on the 50th day,collecting serum and isolating bone marrow derived macrophages(BMDM),which were marked as BMDM1.②Trained immunity model establishment and groups:BMDM were isolated from normal DBA/1J mice,and were pretreated with histone H3K27 demethylases inhibitor(GSKJ1)or PBS for 2 h.Then,serum from CIA model mice in vivo was incubated for 24 h,and the samples were grouped as follows:(CIA+GSH)+PBS group,(CIA+GSH)+GSKJ1 group,(CIA+PBS)+PBS group,(CIA+PBS)+GSKJ1 group.Lipopolysaccharide(LPS)was adopted to stimulated cells on the 6th day,which were marked as BMDM2.③RNA sequencing was used to detect differentially expressed genes(DEGs)and their function in BMDM1 and BMDM2.q-PCR was adopted to estimate the mRNA levels of PFK and Idh3g.The culture supernatants were used to measure the protein levels of TNF-α and IL-6 by ELISA.Results:①Compared with CIA+PBS group,the mice in CIA+GSH group showed lighter of joint swelling(P<0.05),less arthritis index(P<0.05),HE staining suggested less inflam-matory cell infiltration,Safranin O-fast green staining showed more chondrocytes,TRAP staining indicated reduced osteoclasts.②In BMDM1,GO analysis showed that DEGs were mainly involved in glutathione derivative metabolic process,IL-6 production,inflammatory response,innate immune response,regulation of primary metabolic process and glycolipid binding,compared with CIA+GSH and CIA+PBS group.In CIA+GSH group,the mRNA level of PFK was significantly decreased(P<0.05),while Idh3g was also significantly up-regulated(P<0.05),and the expression of TNF-α,IL-6 were both reduced(P<0.05)compared with CIA+PBS group.③In BMDM2,GO analysis showed that DEGs were also involved in inflammatory response,activation of innate immune response,regulation of tumor necrosis factor production,positive regulation of IL-6 production,regulation of glycolytic process and 1,3-β-D-glucan binding between CIA+GSH and CIA+PBS group.Furthermore,in(CIA+GSH)+PBS group,PFK was decreased(P<0.05),Idh3g was up-regulated(P<0.05),and IL-6 was also significantly down-regulated(P<0.05)compared with(CIA+PBS)+PBS group.However,there was no significant difference in the expression of Idh3g and PFK,moreover,TNF-α and IL-6 were significantly up-regulated compared with(CIA+GSH)+GSKJ1 group and(CIA+GSH)+PBS group.Conclusion:GSH can regulate glycometabolism and inflammatory response of macrophages via demethylation of histone H3K27,and it can also alleviate CIA in mice.

Although it has high resolution for soft tissues,magnetic resonance imaging(MRI)is not the standard for chest imaging,which results in an insufficient amount of expert-annotated MRI data.Therefore,CT image is usually converted into MRI image.To overcome the difficulty of obtaining the corresponding modal CT and MRI images,a CSCGAN model with CycleGAN as the framework is proposed based on the structural characteristics of generative adversarial networks.Considering the possibility of mode collapse in CycleGAN,StyleGan2 which can control the style and feature details of the synthetic image and realize the synthesis of high-resolution images is integrated into CycleGAN for reconstructing the generator.A noise module is introduced to reduce external interference.In addition,in order to prevent the loss of tumors during conversion,the discriminator structure of the network is modified,and a mixed attention mechanism is added.Experimental results show that compared with the images generated by other methods,those generated by the proposed model are improved in Dice similarity coefficient,Hausdorff distance,volume ratio and mean intersection over union,indicating that the proposed method can effectively realize the mode conversion of liver tumor images,and that the generated data can improve the segmentation accuracy.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective To investigate the molecular epidemiology of human immunodefieiency viruses (HIV)-1 infected individuals in Honghe district,Yunnan Province and provide the evidence of molecular biology features of HIV-1 infection.Methods HIV-1 pol gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR).Then sequencing and phylogenetic tree analysis were employed tO determine HIV-I subgenotype.The sequence alignment was performed in the database of international drug resistance tO identify resistance-associated mutations.Results The samples from 60 HIV-1 infected individuals were investigated:39 were male,21 were female,with average age 35.5 years old.Thirty-four cases were infected with HIV-I through intravenous drug abuse,12 by sexual contacts,2 were contaminated blood/blood products transfusion and 12 with unknown transmission routes.Phylogenetic analysis revealed that 53 cases (88.3%) were subtype 08-BC,6 (10.0%) were subtype 07-BC and 1 (1.7%) was subtype 01_AE.The total rate of drug resistance associated mutations was 33.3%.The major mutations in protease (PR) and reverse transcriptase (RT) regions accounted for 5.0% and 3 1.7%,respectively.The major mutations in PR region were I541M,V82VFIL,M46MI,which were found in 1 case,respectively.The mutations in RT region were as follows:4 cases were T69D,6 were A62V,1 was D67DE,1 was E44D,3 were V179D,1 was V179E.1 was K238KN,1 was L234T+P236S and 1 was V106E.Conclusions The major transmission route of HIV-I infection in Honghe district,Yunnan Province is through drug injection.The major HIV-1 subtype of HIV-infeeted individuals is 08_BC.PR inhibitor and RT inhibitor drug resistance associated mutations in HlV-1 gene have already existed.

Objective:To investigate the impact of the CD4+CD25nt/hiCD127lo regulatory T cell subset frequency on the immune status and disease progression of Chinese HIV-1 infected individuals.Methods:83 untreated HIV-infected individuals and 312 healthy control individuals of four distinct age groups were enrolled in the research. The CD4+ T cell absolute counts, phenotypes and frequency determination of CD4+CD25nt/hiCD127lo Regulatory T cell subsets was performed on freshly obtained whole blood samples by 3-color immune staining flow cytometry. The HIV-1 specific cellular immune function was test at single cell level by ELISpot. The corresponding plasma viral load was determined by NASBA.Results:The frequency of peripheral CD4+CD25nt/hiCD127lo regulatory T cells of HIV infected individuals in distinct disease progression status was dissimilar in China , and significantly increased in contrast to the healthy controls(P