1.Association between intestinal barrier disruption in liver failure and the cGAS-STING signaling pathway
Qiao TANG ; Chao ZHOU ; Ning ZHANG ; Man GONG
Journal of Clinical Hepatology 2025;41(3):574-579
Liver failure is a common severe syndrome of liver diseases with high mortality. The function and structural integrity of the intestinal barrier as an entity are closely associated with the development and progression of liver failure. The cGAS-STING signaling pathway can participate in innate immune response by recognizing DNA produced by pathogen invasion and host cell damage and inducing the production of type I interferon. Numerous studies have shown that activation of the cGAS-STING pathway can significantly impact the cellular structure, mucosal components, and commensal bacteria of the intestinal barrier. This article reviews the interplay between the cGAS-STING signaling pathway and intestinal barrier disruption in liver failure, in order to provide novel insights for the clinical management of liver failure.
2.General considerations for the design of bioequivalence studies of etomidate medium/long-chain fat emulsion injection
Na AN ; Dong LI ; Li-Li LIU ; Fang LI ; Li-Li HA ; Man-Ru REN ; Yu ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(10):1541-1544
Etomidate reversibly blocks 11-β-hydroxylated steroid dehydrogenase inhibits the synthesis of cortisol by adrenal cells.This product is a special injection.When evaluating the quality and efficacy of the generic and the reference preparations,it should be based on pharmaceutical and non-clinical consistency and adopt a step-by-step research strategy,firstly,bioequivalence(BE)was studied.In bioequivalence study,the research type,dosage and method,bioequivalence evaluation,safety monitoring and pharmacodynamics(PD)evaluation should be considered and designed reasonably.Based on the pharmacokinetics(PK)characteristics of etomidate medium-long chain fat emulsion injection and the bioequivalence study of its generic drug before its domestic market,the general design requirements and relevant considerations for the bioequivalence study of this product were systematically discussed.The purpose is to provide useful reference and guidance for domestic research and development of generic drugs.
3.Study on insulin resistance induced by supernatant of bone marrow mesenchymal stem cells derived from diabetic mice
Bao-Juan LI ; Ke-Chun ZHOU ; ABUDOULA·Mi-re-he-mai-ti ; ZULIHUMA·Re-he-man ; Yu-Meng YE ; Yan-Zhi ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(14):2033-2037
Objective To investigate the role of bone marrow mesenchymal stem cells derived from diabetic mice and their paracrine roles in inducing insulin resistance(IR).Methods The mouse model of diabetes mellitus was established,bone marrow mesenchymal stem cells(BMSC)were extracted and cultured,and the culture supernatant(M-BMSC-CS)was collected.(1)Cell experiment:HepG2 hepatocytes were divided into normal low-glycemic culture group[cultured with low-glycemic DMEM(5.55 mmol·L-1)],M-BMSC-CS experimental group(M-BMSC-CS 75 μL),and high-glycemic and high-lipid control group(given 25 mmol·L-1 high-glycemic DMEM+0.25 mmol·L-1 palmitic acid);(2)Animal experiments:Mice were divided into normal mice group(0.9%NaCl by intraperitoneal injection)and M-BMSC-CS-m group(M-BMSC-CS by intraperitoneal injection of normal mice(injection dose 0.2 mL/10 g)].Glucose intake was measured by glucose oxidase method.The fluorescence intensity of Glut2 protein was detected by immunofluorescence.The expression of insulin signaling pathway protein was detected by Western blot.Test oral glucose tolerance(OGTT)and insulin tolerance(ITT).Results The glucose intakes of the normal low-glucose culture group,the M-BMSC-CS experimental group and the high-glucose and high-lipid control group were(2.96±0.05),(1.64±0.28)and(1.42±0.32)mmol·L-1,respectively;the fluorescence expressions of glucose transporter 2(Glut2)were 53.21±2.70,30.95±3.39 and 34.96±7.60,respectively;the protein expression levels of phosphorylated insulin receptor substrate 1-ser307(p-IRS-1ser307)were 0.46±0.21,1.09±0.24 and 0.91±0.16,respectively;phosphorylated protein kinase(p-AKT)protein expression levels were 0.94±0.05,0.59±0.06 and 0.53±0.05;Glut2 protein expression levels were 1.08±0.14,0.58±0.14 and 0.62±0.09,respectively.The above indexes in M-BMSC-CS experimental group were statistically significant compared with those in normal low-glycemic culture group(all P<0.05).Fasting blood glucose levels in the normal group and M-BMSC-CS-m group were(5.23±0.57)and(9.30±1.14)mmol·L-1;p-AKT protein expression level were 1.27±0.21 and 0.51±0.19;Glut2 protein expression level were 1.17±0.17 and 0.79±0.09,respectively.The above indexes in M-BMSC-CS-m group were significantly different from those in normal mouse group(P<0.05).Conclusion BMSC culture supernatant from diabetic mice induced insulin resistance of normal HepG2 hepatocytes in vitro and normal mice in vivo.
4.Effects of sodium acetate on lowering uric acid and renal protection in mice with hyperuricemic nephropathy
Xue-Man LIN ; Shi-Qi ZHONG ; Yong-Mei LI ; Xiao-Yi QIN ; He-Yang JIANG ; Jia-Xin ZHOU ; Jian-Xin PANG ; Ting WU
The Chinese Journal of Clinical Pharmacology 2024;40(15):2222-2226
Objective To investigate the renal protective effect and mechanism of sodium acetate(Ace)on hyperuricemic nephropathy(HN)in mice.Methods Uric acid nephropathy mice model was prepared by intraperitoneal injection of potassium oxonate combined with adenine gavage.Mice were divided into blank control group(0.9%NaCl+0.5%carboxymethyl cellulose sodium),Ace group(200 mmol·L-1 Ace+0.5%carboxymethyl cellulose sodium),model group(0.9%NaCl+350 mg·kg-1 potassium oxonate+70 mg·kg-1 adenine),and experimental group(based on model group with additional 200 mmol·L-1 Ace).Serum and urine uric acid(UA)and serum creatinine(SCr)levels were observed in each group.Real-time fluorescence quantitative reverse transcription-polymerase chain reaction(qRT-PCR)was used to detect the expression levels of kidney injury molecule-1(Kim-1)and anti-aging gene Klotho,renal fibrosis markers Collagen Ⅰ and Fibronectin,intestinal inflammation-related factors interleukin-1 β(IL-1 β),and mRNA expression levels of tight junction proteins Zo-1.Results The serum UA levels of blank control group,Ace group,model group,and experimental group mice were(259.52±24.40),(227.71±35.91),(604.06±73.55),and(496.24±30.16)μmol·L-1,respectively;SCr levels were(16.85±0.40),(16.18±0.94),(22.38±1.56),and(19.78±1.43)μmol·L-1;Kim-1 mRNA relative expression levels were 1.04±0.25,1.17±0.28,13.00±2.87,and 4.24±3.92;Klotho mRNA relative expression levels were 1.04±0.15,1.02±0.18,0.43±0.12,and 0.69±0.12;Collagen Ⅰ mRNA relative expression levels were 1.05±0.15,1.02±0.18,3.19±1.09,and 1.61±0.55;Fibronectin mRNA relative expression levels were 1.07±0.18,1.02±0.25,7.86±2.40,and 3.34±2.10;intestinal IL-1β mRNA relative expression levels were 1.00±0.01,1.01±0.03,2.55±0.63,and 1.21±0.28;intestinal Zo-1 mRNA relative expression levels were 1.00±0.07,1.07±0.09,0.54±0.20,and 0.92±0.17.The above indicators in blank control group compared with model group,and experimental group compared with model group,all showed statistically significant differences(P<0.05,P<0.01,P<0.001).Conclusion Sodium acetate can effectively reduce UA levels in HN mice,significantly improve renal injury and fibrosis,and its mechanism may be related to the improvement of intestinal inflammatory response and up-regulation of intestinal Zo-1/Occuludin pathway to reduce intestinal mucosal permeability.
5.Interpretation of the Shanghai Standards for the Development of Health-promoting Hospitals
Wei JIN ; Xiaomin WEI ; Huilin LIU ; Jingfeng ZHOU ; Tingfang MAN ; Zongmin JIANG
Shanghai Journal of Preventive Medicine 2024;36(7):633-637
The development of health-promoting hospitals is an important part of the Healthy China Initiative, facilitating the transformation of medical institutions from a primary focus on medical and surgical treatments to a patient-centered approach prioritizing public health. To promote the scientific, standardized, and sustainable development of health-promoting hospitals, the Shanghai Municipal Center for Health Promotion, together with Shanghai General Hospital and other institutions, has jointly developed the Standards for the Development of Health⁃promoting Hospitals (Standards) in accordance with the principles of scientific rigor, feasibility, and advancing with the times. The Standards outlines the requirements for the development of health-promoting hospitals across four aspects: organizational and institutional guarantees, creation of a healthy environment, implementation of health education and promotion, and evaluation. It is applicable to all levels and types of public medical institutions in Shanghai, and can also be referred to and implemented by other medical institutions. The introduction of the Standards is of great significance for promoting the formation of a long-term mechanism in health-promoting hospitals. This paper introduces the basis, principles, main content, precautions, and implementation suggestions of the Standards. Taking into account relevant policies and standards, it interprets the technical aspects in the process of developing health-promoting hospitals, which is helpful for medical institutions and their management to better understand and apply the standards in their work.
6.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
OBJECTIVE:
To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
METHODS:
Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
RESULTS:
TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
CONCLUSIONS
TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male
;
Animals
;
Mice
;
Tripterygium
;
Psoriasis/drug therapy*
;
Keratinocytes
;
Skin Diseases/metabolism*
;
Cytokines/metabolism*
;
Imiquimod/metabolism*
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Dermatitis/pathology*
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Disease Models, Animal
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Mice, Inbred BALB C
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Skin/metabolism*
7.Two new isocoumarins from cave-derived Metarhizium anisopliae NHC-M3-2
Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
Extracting extracts of secondary metabolites from the karst cave fungus
8.The Correspondence between Five Zang Organs and Five Phases and the Order of Five Zang Organs as Seen in Unearthed Literature
Man GU ; Qi ZHOU ; Minmin YAN
Journal of Traditional Chinese Medicine 2024;65(19):1957-1962
The correspondence between the five zang organs and the five phases exhibited variations in the previous and the current literature, which is related to the understanding and interpretation of the historical construction of the basic theories of traditional Chinese medicine, and is an important issue that has been debated for a long time in the history of academia but has not been resolved. Through combing and analyzing the relevant literature handed down during the pre-Qin and Han dynasties, which includes Master LYU's Spring and Autumn Annals (《吕氏春秋》), The Book of Rites: Monthly Ordinances (《月令》), Huainanzi (《淮南子》), Records of the Grand Historian: Biography of BIAN Que and CANG Gong (《史记·扁鹊仓公列传》), The Inner Canon of Yellow Emperor (《黄帝内经》), as well as excavated literature like the Warring States bamboo slips Tang Zai Chi Men (《汤在啻门》) collected by Tsinghua University, Taichan Shu (《胎产书》) unearthed from the Mawangdui Han Dynasty Tombs, Tianhui Medical Manuscripts (《天回医简》) unearthed from the Han Dynasty Tombs of Lao Guan Mountain, Chengdu, this paper finds that the current five phases are newly proposed by previous medical practitioners on the basis of the objective understanding of the physiology and pathology of the five zang organs, which is a unique contribution of traditional Chinese medicine to the traditional Chinese culture. The lacquered acupuncture figurine unearthed from the Han Dynasty Tombs of Lao Guan Mountain, Tianhui Town, Chengdu, Sichuan Province, is engraved on its back with the inscriptions of "heart, lungs, liver, stomach, and kidneys", which refer to the back-Shu points of the five zang organs, and the order follows the sequence of “fire - metal - wood - earth - water”, which is the order of the five phases being restricted. It is believed that this is a reflection of the idea of “heart is the head of the five organs” in the early medical scriptures, which can be used as a basis for judging the chronological order of the relevant chapters of the modern version of The Inner Canon of Yellow Emperor. This order is also seen in the Tianhui Medical Manuscripts unearthed from the same tombs as the acupuncture figurine and is preserved in many chapters of the modern version of The Inner Canon of Yellow Emperor.
9.The relationship between activities of daily living and mental health in community elderly people and the mediating role of sleep quality
Heng-Yi ZHOU ; Jing LI ; Dan-Hua DAI ; Yang LI ; Bin ZHANG ; Rong DU ; Rui-Long WU ; Jia-Yan JIANG ; Yuan-Man WEI ; Jing-Rong GAO ; Qi ZHAO
Fudan University Journal of Medical Sciences 2024;51(2):143-150
Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
10.Recognition of intestinal mucosal immunopathogenesis of IgA nephropathy: gut-derived IgA + plasma cells
Chinese Journal of Applied Clinical Pediatrics 2024;39(3):232-235
Gut-derived IgA + plasma cells are the key to intestinal mucosal immunity.The intestinal flora and diet regulate the production of gut-derived IgA + plasma cells, which not only play an immune role in the intestinal mucosa, but also migrate to tissues or organs outside the intestine to regulate immune and inflammatory reactions by relying on the production of IgA antibodies or the secretion of cytokines and other non-antibody effects, and act as a protective or pathogenic factor in various diseases.The pathogenic effect of intestinal mucosal immune imbalance in IgA nephropathy (IgAN) has been a concern.IgA + plasma cells increase in intestinal lamina propria of high serum IgA mice with the increase of abnormally glycosylated IgA1.The long-lived plasma cells increase, and interleukin-6 is inhibited in IgAN patients.However, it remains unclear whether gut-derived IgA + plasma cells migrate to kidneys to promote disease progression.This article reviews the relevant research progress on the immunopathologic effects and mechanisms of gut-derived IgA + plasma cells in the intestinal mucosa of IgAN.

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