1.2,6-dimethoxy-1,4-benzoquinone alleviates dextran sulfate sodium-induced ulcerative colitis in mice by suppressing NLRP3 inflammasome activation.
Chenfei LIU ; Wei ZHANG ; Yao ZENG ; Yan LIANG ; Mengting WANG ; Mingfang ZHANG ; Xinyuan LI ; Fengchao WANG ; Yanqing YANG
Journal of Southern Medical University 2025;45(8):1654-1662
OBJECTIVES:
To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice.
METHODS:
Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ+ CD8+ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry.
RESULTS:
In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ+ CD8+ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis.
CONCLUSIONS
DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals
;
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism*
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Mice, Inbred C57BL
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Colitis, Ulcerative/metabolism*
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Dextran Sulfate/adverse effects*
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Male
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Inflammasomes/metabolism*
;
Mice
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Benzoquinones/therapeutic use*
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Th17 Cells
;
Caspase 1/metabolism*
2.Effects of long-snake moxibustion combined with modified Duhuo Jisheng Decoction on inflammatory factors and lumbar function in patients with liver-kidney deficiency pattern of lumbar disc herniation
Mingfang LYU ; Xiaoyan ZHU ; Kangmin WAN ; Yan WANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1171-1176
Objective This study aimed to investigate the clinical effect of long-snake moxibustion combined with modified Duhuo Jisheng Decoction in the treatment of the liver-kidney deficiency pattern of lumbar disc herniation. Methods All patients with liver-kidney deficiency pattern of lumbar disc herniation admitted to Nanchang Hongdu Hospital of Traditional Chinese Medicine from March 2021 to April 2023 were assigned the control group and the experimental group by random number table method,with 68 cases in each group. The control group was treated with conventional Western medicine,and the experimental group was treated with long-snake moxibustion combined with modified Duhuo Jisheng Decoction based on the control group for four consecutive weeks. Observe the clinical efficacy,the Japanese Orthopedic Association (JOA) score,and traditional Chinese medicine syndrome score of two groups of patients. Detect the serum levels of prostaglandin E2 (PGE2),transforming growth factor-β 1 (TGF-β1),interleukin-1β (IL-1β),matrix metalloproteinase-2 (MMP-2),and hypoxia-inducible factor-1α (HIF-1α) in two groups of patients. Results Compared with the control group (79.41%),the clinical efficaly of experimental group (94.12%) was increased (P<0.05). Compared with before treatment,TCM syndrome score of 2 groups was decreased,JOA score was increased,serum PGE2,TGF-β1,MMP-2,HIF-1α,and IL-1β were decreased after treatment (P<0.05). After treatment,compared with control group,TCM syndrome score of experimental group was decreased,JOA score was increased,serum PGE2,TGF-β1,MMP-2,HIF-1α,and IL-1β were decreased (P<0.05). Conclusion Long-snake moxibustion combined with modified Duhuo Jisheng Decoction can significantly reduce the inflammatory response of patients with liver-kidney deficiency pattern of lumbar disc herniation,inhibit the secretion of pain mediators,improve lumbar function,and thus improve clinical efficacy.
3.Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China
Rong LIU ; Zhicai YU ; Changxue XIAO ; Shufang XIAO ; Juan HE ; Yan SHI ; Yuanyuan HUA ; Jimin ZHOU ; Guoying ZHANG ; Tao WANG ; Jianyu JIANG ; Daoxue XIONG ; Yan CHEN ; Hongbo XU ; Hong YUN ; Hui SUN ; Tingting PAN ; Rui WANG ; Shuangmei ZHU ; Dong HUANG ; Yujiang LIU ; Yuhang HU ; Xinrui REN ; Mingfang SHI ; Sizun SONG ; Jumei LUO ; Juan LIU ; Juan ZHANG ; Feng XU
Chinese Journal of Pediatrics 2024;62(3):204-210
Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.
4.Application and design of lymphoma dataset based on real-world research
Lan MI ; Meng WU ; Feier FENG ; Tingting DU ; Luersulitan REYIZHA ; Mengmeng LIN ; Mingfang NIU ; Yuqin SONG ; Yan XIE ; Jun ZHU
Chinese Journal of Medical Science Research Management 2023;36(1):18-23
Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.
5.Mechanism of blood brain barrier in the pathogenesis and therapeutics of multiple sclerosis
Yan JIA ; Yue HUANG ; Jiewen ZHANG ; Junkui SHANG ; Mingfang ZHU ; Xiaodi HAO
Chinese Journal of Neurology 2022;55(6):655-658
Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating diseases of the central nervous system, the underlying cause of which has not been cleared. Previous studies have shown that the pathogenesis of MS is related to the destruction of blood brain barrier, furthermore the drugs used to treat MS have a certain protective effect on the function of blood brain barrier. Therefore, this review combines the research progress at home and abroad to clarify the relationship between the blood brain barrier and MS in pathogenesis and treatment, proposing possible orientation of development.
6.Long-term effect of neoadjuvant imatinib for locally advanced gastrointestinal stromal tumor
Zhenmeng LIN ; Mingfang YAN ; Yi WANG ; Shenghong WEI ; Jintian SONG ; Qilin GONG ; Luchuang CHEN ; Huizhe ZHENG
Chinese Journal of General Surgery 2019;34(4):315-318
Objective To explore the safety and long-term results of preoperative imatinib mesylate administration (IM) in patients with locally advanced gastrointestinal stromal tumors (GIST).Methods From Sep 2009 to Nov 2016,locally advanced GIST patients treated in Fujian Medical University Cancer Hospital were analysed retrospectively.Result 34 patients were included.Preoperative median IM treatment was 27 weeks(range 12-71 weeks).65% patients had a partial response to IM,35% showed stable disease.All patients underwent surgical R0 resection.The complication rate was 9% and no death occurred within 30 days post operation.The median follow-up time was 62.2 months (range of 13-89 months).20 patients continued to take imatinib orally,14 patients did not.The 3 year survival rate of patients undergoing surgery was 67%.Univariate analysis showed that tumor location,preoperative imatinib effect,pathology,targeted therapy after surgery were factors affecting prognosis.Multivariate analysis show that the independent risk factors affecting prognosis were tumor location,pathology,targeted therapy after surgery.Conclusion In locally advanced GISTs,preoperative IM is useful and safe that can effectively decrease tumor size,facilitating resection.
7.Clinicopathological features analysis of common complications in pediatric liver transplantation
Zhenglu WANG ; Zhandong HU ; Wenjuan CAI ; Chao SUN ; Wei GAO ; Zhiqi YIN ; Xuexi GUO ; Yan LI ; Mingfang ZHANG ; Lei LIU ; Zhongyang SHEN
Chinese Journal of Organ Transplantation 2018;39(9):527-533
Objective The purpose of this study was to explore common complications and their clinicopathological features in pediatric liver transplantation.Methods Clinical and pathological data of 240 liver biopsies from 168 children that conducted liver puncture from January 2015 to May 2018 in Tianjin First Central Hospital was retrospectively analyzed.We comprehensively analyzed incidence rate and pathological features of various complications,and correlations between acute rejection and C4d staining result or Banff score.Results A total of 86.67% (208/240) liver biopsies could be definitely diagnosed with incidence rate of main complications in descending order as follows:T cell mediated rejection (TCMR) 60.57% (126/208),drug-induced liver injury (DILI) 17.31% (36/208),biliary complication 8.17% (17/208),vascular complication 3.37% (7/208),ischemia/reperfusion injury (IRI) 2.88% (6/208),antibody mediated acute rejection (AMR) 1.92% (4/208),HBV infection 1.92% (4/208),non-alcoholic fatty liver disease (NAFLD) 1.44% (3/208),chronic rejection (CR) 0.96 % (2/208) and HCV infection 0.48 % (1/208).TCMR and AMR in acute rejection (AR) accounted for 96.92% (126/130) and 3.08% (4/160),and into(portal-based,PB)type TCMR accounted for 96.03%(121/126) with the detectable rate of BP type subtype TCMR of 26.45%(32/121)within 30 d.There were 65.87% (83/126)、25.40% (32/126) 和4.76% (6/126) of BP TCMR samples with "Banff ACR RAI" score within 3-5,6-7 and 8-9,and RAI score was negatively correlated with postoperative time (r =0.127,P =0.084).The incidence rate of central perivenulitis (CP) and portal eosinophils infiltration (PEI) in BP TCMR was 63.63% (77/121) 和43.80% (53/ 121),respectively,additionally,the PEI level was positively correlate with RAI score (P<0.05).CP TCMR and AMR occurred within 30d-365 d and 8 d-180 d,respectively postoperative,while,the two CR occurred at 1095 d and 1335 d postoperative,and significant correlation was strikingly observed between rejection subtype and postoperative time (Z =9.231,P =0.026).C4d positive rate was 10% (24/240),which was associated with Banff score and postoperative time,besides,C4d score was also correlated with rejection subtype and RAI score.The occurrence of DILI was mainly at time of <90 d or >180 d postoperative,and the detectable rate of biliary complication within 180 d postoperative was 82.35% (14/17),IRI Appear in <30d.Hepatic artery complication account for nearly 57.14% (4/7),occurrence time is ≤90 d.Occurrence of HBV infection,CMV infection and NAFLD were mainly at >365 d,<90 d and <365 d,respectively.Conclusion There were lots of differences in clinical and pathological features among multi pediatric liver transplantation complications.Liver puncture plays an important role in rejection subtype classification and grading,as well as in non-rejection complications identification.
8.Risk factors and prognostic value of anastomotic leak in gastric cancer patients undergoing total gastrectomy
Zhenmeng LIN ; Huizhe ZHENG ; Mingfang YAN ; Changhua ZHUO ; Yangming LI
Chinese Journal of General Surgery 2018;33(10):817-820
Objective To analyze the risk factors for anastomotic leak after total gastrectomy in gastric cancer patients and its impact on patients survival.Methods A total of 1 547 gastric cancer patients who underwent curative resection between 1999 to 2016 were enrolled.Results The anastomotic leak occurred in 106 of 1 547 patients;and it was happened at a median of (6.0 ± 2.1) day after surgery.The median postoperative hospital stay was (9 ± 3) days for non-anastomotic leak,lower than patients for anastomotic leak with (15 ± 5) days.The anastomotic leak was significantly correlated with age,lung function,BMI,serum albumin,intraoperative blood loss,operative time,smoking and diabetes (P <0.05).Multivariable analysis showed that the anastomotic leak was significantly correlated with diabetes,lung function,smoking (P < 0.05).The 30-day mortality with anastomotic leak was lower than patients without leak.The 3'-and 5-year survival rate of patients with anastomotic leak were 53.9% and 47.7%,significantly lower than those of 69.4% and 58.5% without anastomotic leak (P < 0.05).By univariate analysis that BMI,pathological stage,tumor size,serum albumin,anastomotic leak were factors affecting prognosis (P < 0.05).While multivariate analysis showed that anastomotic leakage was independently associated with worse overall survival.Conclusion Anastomotic leakage in patients who underwent total gastrectomy increases the 30-day mortality and associated with poorer 5-year survival.
9.Effect of community nursing training
Mingfang WANG ; Xiaoyan DENG ; Ning YAN
Modern Clinical Nursing 2017;16(3):45-48
Objective To explore the contents and modes of community nursing training and improve community care quality.Methods The training course and assessment standard were worked out according to practical work in community health service centers,including basic nursing skills,community first aid skills,hospital infection control skills,preventive health care skills and community document management skills.Toally 58 nurses from 11 community health service centers were trained for 36 hours from January to June,2016 and tested before and after training to assess the effect of training.Result After training,the scores on all skills were significantly higher than those before training (all P<0.01).Conclusion Regular and practical training and management are the guarantee for the improvement of the community care quality.

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