1.Effect of apoptosis inhibitor of macrophage in inflammatory reactions and lipid metabolic diseases
Fan ZHANG ; Chunyu TIAN ; Jingcun WANG ; Xiaojin LA ; Qianru FU ; Jie LI ; Wenhao FU
Chinese Journal of Comparative Medicine 2024;34(3):142-148
Apoptosis inhibitor of macrophage(AIM)belongs to group B of the scavenger receptor cysteine rich-super family.AIM is a soluble protein secreted by macrophages.The expression of this protein is controlled by the liver X receptor.AIM,which is secreted by macrophages,plays important and broad roles in the immune responses of the body.It not only inhibits the apoptosis of macrophages but also participates in the regulation of macrophage polarization.In addition,studies have revealed that AIM is involved in various physiological and pathological processes,such as inflammation,obesity,atherosclerosis,and cancer.It has been used as a biological marker for the diagnosis of diseases such as tuberculosis and liver cirrhosis.Moreover,it can promote the lipolysis of adipose cells by inhibiting the activity of fatty acid synthase(FAS),playing an important role in the regulation of lipid homeostasis,lipid metabolism,and autoimmune diseases.In this paper,we review the multiple functional characteristics of AIM and its effects on inflammation,lipid metabolism,and related diseases to provide a theoretical basis for relevant medical research.
2.Association of CD4+ T lymphocyte count and gingival crevicular fluid prostaglandin E2 with periodontal parameters in HIV-positive periodontitis patients
Hongcheng JIA ; Xuan WANG ; Wenhao HUA ; Xiaoguang LI ; Wen HOU ; Qian FU
Chinese Journal of Stomatology 2014;49(2):73-77
Objective To investigate the correlation of CD4+ T lymphocyte count and prostaglandin E2 (PGE2) in gingival crevicular fluid(GCF) with periodontal status in HIV-positive patients with periodontitis.Methods Twenty subjects were selected according to inclusion criteria.The plasmatic CD4+ T lymphocytes were counted.All the individuals were divided into three groups,group A (CD4+ T lymphocyte count <200 cell/mm3),group B (200 cell/mm3 ≤CD4+ T lymphocyte count≤500 cell/mm3) and group C (CD4+ T lymphocyte count > 500 cell/mm3).Periodontal indexes,including plaque index (PLI),bleeding index(BI),attachment level(AL) and probing depth(PD) were recorded.GCF samples were taken from 120 index teeth by means of sterile paper strips.GCF PGE2 levels were determined by radioimmunoassays.MannWhitney was used to compare the periodontal indexes and PGE2 levels among the three groups.Partial correlations and Spearman correlations were applied to analyze the correlation of CD4+ T lymphocytes count and PGE2 in gingival crevicular fluid with periodontal status.Results BI value,PGE2 concentration and total PGE2 were 3.00 (2.00),90.75 (30.60) μg,/L,447.58 (243.08) pg in group B,which were higher than those in group A[2.00(1.25),79.75(30.50) μg/L and 339.52(200.97) pg respectively] and group C [2.00(1.00),73.38 (14.83) μg/L and 299.18 (108.33) pg respectively] (P < 0.0167).But the differences of PD and AL among the three groups were not significantly different (P > 0.0167).The correlations were observed between CD4+ T lymphocyte count and BI for the subpopulations with CD4+ T lymphocyte count < 200 cells/mm3 (r =0.657,P < 0.05) and between 200-500 cells/mm3 (r =-0.369,P < O.05).PGE2 concentration was negatively correlated with BI,PD and AL(P < 0.05),and total PGE2 was positively correlated with PD and AL (P < 0.05).Conclusions There was an association between the periodontal status and CD4+ T lymphocyte count in HIV + patients.GCF PGE2 level was related to periodontal parameters including BI,PD and AL.
3.Clinical characteristics and electron transfer flavoprotein dehydrogenase genetic mutations in 26 patients with riboflavin reactive lipid deposition myopathy
Haiyan LIU ; Jun FU ; Mingming MA ; Qianqian QU ; Qi QIAN ; Wenhao CUI ; Yan ZHANG ; Haidong LYU
Chinese Journal of Neuromedicine 2022;21(5):486-491
Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.
4.Imaging manifestation of crossed ectopic fused kidney
Liuliu ZHANG ; Wenhao FU ; Mengya SUN ; Guanglei TANG ; Jian GUAN
Chinese Journal of Medical Imaging Technology 2024;40(2):261-265
Objective To explore imaging manifestations of crossed ectopic fused kidney.Methods Data of 12 patients with crossed ectopic fused kidney were retrospectively analyzed,and the imaging manifestations of crossed ectopic fused kidney were observed.Results L type crossed ectopic fused kidney was detected in 5 cases,while inferior ectopic type(Ii type),S-shaped type and lump type(O type)ectopic fused kidney was found each in 2 cases,respectively,and doughnut or disc type(C-C type)ectopic fused kidney was noticed in 1 case.The ectopic fused kidney presented with empty one side renal cavity,while the morphology and position of the contralateral kidney were generally normal in all 12 cases,which crossed the midline and fused with the contralateral in situ kidney,including right to left crossed ectopic fusion in 8 cases and left to right crossed ectopic fusion in 4 cases.The ureters of the crossing kidney went across the midline,opened into the bladder trigone on the contralateral side in 11 cases or prostate in 1 case.Combined reproductive system abnormalities were found in 3 cases,including unicornous uterus,bicornuate uterus and cryptorchidism each in 1 case.Two cases were found complicated with abnormal inferior vena cava,including 1 case of both side inferior vena cava and 1 case of left inferior vena cava.Conclusion The imaging manifestations of crossed ectopic fused kidney had characteristics.Complete displaying of reveal fused kidney,ureteral course and opening was helpful to accurate diagnosis and classification of crossed ectopic fused kidney.
5.The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma: a multicenter real-world study in China
Yang YANG ; Zhongjun XIA ; Wenhao ZHANG ; Chengcheng FU ; Li BAO ; Bing CHEN ; Kaiyang DING ; Sili WANG ; Jun LUO ; Bingzong LI ; Luoming HUA ; Wei YANG ; Xin ZHOU ; Liang WANG ; Tianhong XU ; Weida WANG ; Guolin WU ; Yun HUANG ; Jing LI ; Peng LIU
Chinese Journal of Hematology 2021;42(8):628-634
Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.
6.Impact of particle size and pH on protein corona formation of solid lipid nanoparticles: A proof-of-concept study.
Wenhao WANG ; Zhengwei HUANG ; Yanbei LI ; Wenhua WANG ; Jiayu SHI ; Fangqin FU ; Ying HUANG ; Xin PAN ; Chuanbin WU
Acta Pharmaceutica Sinica B 2021;11(4):1030-1046
When nanoparticles were introduced into the biological media, the protein corona would be formed, which endowed the nanoparticles with new bio-identities. Thus, controlling protein corona formation is critical to
7.Targeting macrophagic 17β-HSD7 by fenretinide for the treatment of nonalcoholic fatty liver disease.
Xiaoyu DONG ; Yiting FENG ; Dongqin XU ; Mengya ZHANG ; Xiao WEN ; Wenhao ZHAO ; Qintong HU ; Qinyong ZHANG ; Hui FU ; Jie PING
Acta Pharmaceutica Sinica B 2023;13(1):142-156
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis. However, which molecule regulates macrophage polarization in NAFLD remains unclear. Herein, we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) expression in hepatic macrophages concomitantly with elevated M1 polarization. Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet (HFD) for 6 weeks revealed that lipid metabolism pathways were notably changed. Furthermore, 17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis, insulin resistance and liver injury. Mechanistically, 17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content, thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines. In addition, to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD, fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity. Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production, and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages. In conclusion, our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.
8.Association between fatty acid consumption and hypertension among rural residents in Hanzhong of Shaanxi Province
Ruru LIU ; Hong YAN ; Yaling ZHAO ; Qiang LI ; Xin WANG ; Han FU ; Fei WANG ; Chen CHEN ; Wenhao LI ; Shaonong DANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(4):617-622
【Objective】 To evaluate the associations of total fat and fatty acid consumption with the risk of hypertension among rural residents in Hanzhong, Shaanxi Province. 【Methods】 A cross-sectional survey on dietary status with a semi-quantitative food frequency questionnaire was conducted among rural residents aged between 18 and 80 years old in Hanzhong of Shaanxi. Multivariate log-binomial regression models and restricted cubic spline were used to explore the associations of dietary total fat, saturated fatty acid, polyunsaturated fatty acid and monounsaturated fatty acids with hypertension and as well as association between dose and response. 【Results】 A total of 2241 individuals were included, with 774 males and 1467 females. Monounsaturated fatty acid accounted for 51.9% of total dietary fat intake, while the other two fatty acids for 48.1%. The intake of dietary fat and any fatty acid in men was significantly in men higher than in women (P<0.001). Results of multivariable log-binomial regression indicated that after adjustment of energy, socio-demographic and lifestyles, the risk of hypertension reduced significantly in Q4 group, compared with that in Q1 (PR: 0.71, 95% CI: 0.54-0.92; P-trend: 0.022) in females. A nonlinear dose-response relationship between monounsaturated fatty acids and hypertension was detected by restricted cubic spline in women (P