1.Effects of metformin on gut microbiota and short-/medium-chain fatty acids in high-fat diet rats.
Ying SHI ; Lin XING ; Shanyu WU ; Fangzhi YUE ; Tianqiong HE ; Jing ZHANG ; Lingxuan OUYANG ; Suisui GAO ; Dongmei ZHANG ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2025;50(5):851-863
OBJECTIVES:
Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats.
METHODS:
Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids.
RESULTS:
Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05).
CONCLUSIONS
Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals
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Metformin/pharmacology*
;
Rats, Sprague-Dawley
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Diet, High-Fat/adverse effects*
;
Rats
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Gastrointestinal Microbiome/drug effects*
;
Male
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Fatty Acids, Volatile/metabolism*
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Fatty Acids/metabolism*
2.Effects of Zhuang Medicinal Thread Moxibustion on Apoptosis of Interstitial Cells of Cajal in Gastric Smooth Muscle of Diabetic Gastroparesis Rats Based on p38MAPK Signaling Pathway
Zibin WANG ; Yushan FAN ; Yu WU ; Hui XU ; Fangzhi ZHANG ; Yujun HE
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(12):97-105
Objective To investigate the effects of Zhuang medicinal thread moxibustion on apoptosis of interstitial cells of Cajal(ICC)in gastric smooth muscle of diabetic gastroparesis(DGP)rats via regulation of the p38MAPK signaling pathway.Methods Totally 60 rats were randomly divided into a blank group(10 rats)and a modeling group(50 rats).DGP models were established in the modeling group via intraperitoneal injection of streptozotocin.50 successfully modeled rats were further randomized into model group,Western medication group,prevention+treatment group,prevention group and treatment group,with 10 rats in each group.The Western medication group was administered mosapride citrate by gavage for 3 weeks starting at week 10;the prevention+treatment group underwent Zhuang medicinal thread moxibustion("Zhongwan",bilateral"Neiguan"and"Zusanli")intervention for 6 weeks starting at week 7;the prevention group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 7;and the treatment group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 10,3 cones per point,once a day;the blank group and model group received handling only.The random blood glucose and body mass of rats were detected,and the gastric emptying rate and intestinal propulsion rate were calculated.HE staining was used to observe the morphology of gastric smooth muscle tissue,TUNEL staining was used to detect the apoptosis of gastric smooth muscle tissue,ELISA was used to detect the contents of Caspase-3,TNF-α,IL-1β and IL-6 in gastric smooth muscle tissue,immunohistochemistry was used to detect the positive expressions of Cx43 and c-kit in gastric smooth muscle tissue,Western blot was used to detect the expressions of p38MAPK,p-p38MAPK,BAX and Bcl-2 protein in gastric smooth muscle tissue.Results Compared with the blank group,the random blood glucose significantly increased in the model group(P<0.01),and the body mass,gastric emptying rate and small intestinal propulsion rate significantly decreased(P<0.01),the blood vessels of gastric tissue were not clear,the surface was not smooth,the mucosal folds were less,the arrangement of gastric smooth muscle cells was disordered,the nuclear membrane was not clear,and there were vacuole like changes between cells,the apoptosis rate significantly increased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the protein expressions of p38MAPK,p-p38MAPK and BAX in gastric smooth muscle tissue significantly increased(P<0.01),and the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio significantly decreased(P<0.01).Compared with the model group,the random blood glucose of rats in each intervention group decreased,and the body mass,gastric emptying rate and intestinal propulsion rate increased(P<0.01),the blood vessels of gastric tissue were clear,the inner surface of stomach was smooth,the mucosal folds were not rich,no ulcer was found,the shape of gastric smooth muscle cells was complete,the nuclear membrane was clear,and the arrangement of muscle cells was regular,the apoptosis rate significantly decreased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the expressions of p38MAPK,p-p38MAPK,BAX protein in gastric smooth muscle tissue decreased(P<0.05,P<0.01),the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio increased(P<0.05,P<0.01).The overall effect of the prevention+treatment group was better than that of the Western medication group,prevention group and treatment group(P<0.05,P<0.01).Conclusion Zhuang medicinal thread moxibustion may reduce gastric inflammation and ICC apoptosis in DGP rats by inhibiting p38MAPK signaling pathway,so as to improve DGP gastric motility disorder,and the effect of early intervention is more significant.
3.Effects of Zhuang Medicinal Thread Moxibustion on Apoptosis of Interstitial Cells of Cajal in Gastric Smooth Muscle of Diabetic Gastroparesis Rats Based on p38MAPK Signaling Pathway
Zibin WANG ; Yushan FAN ; Yu WU ; Hui XU ; Fangzhi ZHANG ; Yujun HE
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(12):97-105
Objective To investigate the effects of Zhuang medicinal thread moxibustion on apoptosis of interstitial cells of Cajal(ICC)in gastric smooth muscle of diabetic gastroparesis(DGP)rats via regulation of the p38MAPK signaling pathway.Methods Totally 60 rats were randomly divided into a blank group(10 rats)and a modeling group(50 rats).DGP models were established in the modeling group via intraperitoneal injection of streptozotocin.50 successfully modeled rats were further randomized into model group,Western medication group,prevention+treatment group,prevention group and treatment group,with 10 rats in each group.The Western medication group was administered mosapride citrate by gavage for 3 weeks starting at week 10;the prevention+treatment group underwent Zhuang medicinal thread moxibustion("Zhongwan",bilateral"Neiguan"and"Zusanli")intervention for 6 weeks starting at week 7;the prevention group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 7;and the treatment group received Zhuang medicinal thread moxibustion for 3 weeks starting at week 10,3 cones per point,once a day;the blank group and model group received handling only.The random blood glucose and body mass of rats were detected,and the gastric emptying rate and intestinal propulsion rate were calculated.HE staining was used to observe the morphology of gastric smooth muscle tissue,TUNEL staining was used to detect the apoptosis of gastric smooth muscle tissue,ELISA was used to detect the contents of Caspase-3,TNF-α,IL-1β and IL-6 in gastric smooth muscle tissue,immunohistochemistry was used to detect the positive expressions of Cx43 and c-kit in gastric smooth muscle tissue,Western blot was used to detect the expressions of p38MAPK,p-p38MAPK,BAX and Bcl-2 protein in gastric smooth muscle tissue.Results Compared with the blank group,the random blood glucose significantly increased in the model group(P<0.01),and the body mass,gastric emptying rate and small intestinal propulsion rate significantly decreased(P<0.01),the blood vessels of gastric tissue were not clear,the surface was not smooth,the mucosal folds were less,the arrangement of gastric smooth muscle cells was disordered,the nuclear membrane was not clear,and there were vacuole like changes between cells,the apoptosis rate significantly increased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the protein expressions of p38MAPK,p-p38MAPK and BAX in gastric smooth muscle tissue significantly increased(P<0.01),and the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio significantly decreased(P<0.01).Compared with the model group,the random blood glucose of rats in each intervention group decreased,and the body mass,gastric emptying rate and intestinal propulsion rate increased(P<0.01),the blood vessels of gastric tissue were clear,the inner surface of stomach was smooth,the mucosal folds were not rich,no ulcer was found,the shape of gastric smooth muscle cells was complete,the nuclear membrane was clear,and the arrangement of muscle cells was regular,the apoptosis rate significantly decreased(P<0.01),the contents of Caspase-3,TNF-α,IL-1β,IL-6 and the expressions of p38MAPK,p-p38MAPK,BAX protein in gastric smooth muscle tissue decreased(P<0.05,P<0.01),the positive expressions of Cx43,c-kit,the protein expression of Bcl-2 and Bcl-2/BAX ratio increased(P<0.05,P<0.01).The overall effect of the prevention+treatment group was better than that of the Western medication group,prevention group and treatment group(P<0.05,P<0.01).Conclusion Zhuang medicinal thread moxibustion may reduce gastric inflammation and ICC apoptosis in DGP rats by inhibiting p38MAPK signaling pathway,so as to improve DGP gastric motility disorder,and the effect of early intervention is more significant.
4.Analysis on Acupoint Selection Rules of Acupuncture in Treating Perimenopausal Syndrome Based on Data Mining
Fangzhi ZHANG ; Yushan FAN ; Furui MIAO ; Yujun HE
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(6):24-31
Objective To explore the acupoint selection rules in the treatment of perimenopausal syndrome(PMS)with acupuncture by using data mining technology.Methods The clinical research literature on acupuncture treatment of PMS was retrieved from CNKI,Wanfang Data,VIP,CBM,Cochrane Library,Embase,PubMed and ScienceDirect from the establishment of the databases to August 16,2023.Excel 2021 was used to establish a prescription database for acupuncture treatment of PMS,and frequency statistics and classification of acupoints were conducted.SPSS Modeler 18.0 and SPSS Statistics 26.0 software were used to conduct association rules,clustering analysis and decision tree analysis,to explore the characteristics and compatibility rules of acupoint selection in acupuncture and moxibustion treatment of PMS.Results Totally 114 articles were included,including 115 acupoint prescriptions,and 108 acupoints with a total frequency of 787.The high-frequency acupoints were Sanyinjiao,Guanyuan,Shenshu,etc.The commonly used meridians were the bladder meridian and Conception Vessel.The majority specific acupoints were intersection acupoints,wu-shu points and back-shu points.The involved acupoints were mostly located in the lower limbs,abdomen and back.Acupuncture techniques often used the method of flat reinforcement and reduction,with the most commonly used waveform of electroacupuncture being the dilatational wave and the duration of needle retention being 10-30 minutes.The decision tree selected three simplified selection paths based on the dependent variable of Guanyuan.The core acupoints group was analyzed,and 14 groups of association rules and 7 effective cluster groups were obtained.Conclusion Acupuncture treatment of PMS follows the therapeutic principles of tonifying the kidney and harmonizing yin and yang.The acupoint combinations and core acupoint groups obtained from data mining can provide reference for clinical and scientific research.
5.Exploration on the Acupoint Selection Law of Acupuncture in Treating Chronic Prostatitis/Chronic Pelvic Pain Syndrome Based on Data Mining
Fangzhi ZHANG ; Yushan FAN ; Furui MIAO ; Yujun HE
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):46-53
Objective To explore the clinical acupoint selection law of acupuncture in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)by data mining.Methods The clinical research literature on acupuncture treatment of CP/CPPS was retrieved from CNKI,VIP,Wanfang Data,China Biology Medicine Database,Embase,PubMed,Cochrane Library and Web of Science from the establishment of the databases to November 17,2023.The prescription database was established using Excel 2021 to perform frequency statistics of acupoints.SPSS Modeler 18.0 and SPSS Statistics 26.0 were used to conduct association rules,factor analysis and clustering analysis,to explore the characteristics and acupoint selection and compatibility law in acupuncture treatment of CP/CPPS.Results A total of 105 articles was included,and 105 acupoint prescriptions were extracted,involving a total of 75 acupoints,with a total frequency of 611 times.The high-frequency acupoints were Zhongji,Sanyinjiao,Guanyuan,etc.The commonly used meridians were Conception Vessel and the bladder meridian.Jiaohui acupoints,Mu acupoints and Wushu acupoints accounted for the vast majority.The involved acupoints were mostly located in the abdomen,lower limbs,and lumbosacral region.The core acupoints was analyzed,and 19 groups of association rules,8 factors and 8 effective cluster groups were obtained.Conclusion Acupuncture treatment of CP/CPPS follows the therapeutic principles of tonifying the kidney,removing dampness,soothing the liver and removing blood stasis.The core acupoints group is Guanyuan-Zhongji-Sanyinjiao,with differentiation of syndromes and compatibility with other acupoints.
6.Analysis of ankylosing spondylitis animal model based on clinical characteristics of traditional Chinese and Western medicine
Fangzhi ZHANG ; Furui MIAO ; Yushan FAN ; Yujun HE
Chinese Journal of Comparative Medicine 2024;34(8):128-138
Ankylosing spondylitis is an autoimmune disease with sacroiliac arthritis and spinal arthritis as the main manifestations.The disease mainly occurs in young men,has a high disability rate,and is a serious threat to the life and health of patients.Biological agents are expensive,and many adverse reactions to hormones,non-steroidal anti-inflammatory drugs,and anti-rheumatic drugs have been recorded.Traditional Chinese medicine can regulate the immunity and anti-inflammatory effects of the disease,and has good clinical effects.To promote the further study of the pathogenesis of ankylosing spondylitis and the development and screening of therapeutic drugs and therapies,in this paper,we summarize the method and mechanisms of modeling of the existing animal model of ankylosing spondylitis and analyze the advantages and disadvantages of the model.To evaluate the agreements between Chinese and Western medicine clinical characteristics,we compare the characteristics of Chinese and Western medical syndromes of the animal model.Building an animal model of ankylosing spondylitis with a higher degree of consistency between traditional Chinese and Western medicine is the key to innovative research into traditional Chinese medicine method of treating ankylosing spondylitis.To lay the foundation for research into traditional Chinese medicines and acupuncture for ankylosing spondylitis,this paper analyzes the degree of concurrence between the Chinese and Western medicine clinical characteristics of animal models.
7.Monkeypox: clinical manifestations, diagnosis, treatment and follow-up
Fangzhi DU ; Xu ZHANG ; Qianqiu WANG
Chinese Journal of Dermatology 2023;56(1):76-81
The world is suffering from the monkeypox epidemic, and China is facing a great risk of monkeypox importation. Understanding and mastering clinical manifestations, diagnosis and treatment of monkeypox is one of the important measures to respond to future crises. This review summarizes updated guidelines and relevant studies, and covers main clinical manifestations, diagnosis, treatment and follow-up of monkeypox patients, as well as management of special populations, aiming to provide references for clinicians and prevention workers.
8.Serum levels of complement B and D in patients with diabetic peripheral neuropathy and their correlation
Qi CHEN ; Jing CHEN ; Fangzhi HU ; Yanfang ZHANG ; Qiuhua LIANG ; Lin SUN
Journal of Chinese Physician 2022;24(3):396-400
Objective:To investigate the serum level and significance of complement factor B (CFB) and complement factor D (CFD) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN).Methods:From October 2019 to October 2020, 110 patients with T2DM in the endocrinology department of Affiliated Hospital of Jining Medical College were divided into DPN group ( n=60) and simple T2DM group ( n=50) according to whether or not DPN was combined. In addition, 52 cases of physical examination population in the physical examination center in the same period were selected as the normal control group ( n=52). The serum levels of CFB, CFD and tumor necrosis factor-α (TNF-α) were measured by enzyme linked immunosorbent assay (ELISA). The correlation between CFB, CFD and clinical indexes was analyzed, and the influencing factors of DPN were analyzed by logistic regression. Results:The serum levels of CFB and CFD in DPN group were higher than those in T2DM group and normal control group [CFB: (845.43±101.10)μg/ml vs (792.19±116.59)μg/ml, (739.20±123.43)μg/ml, P<0.05], [CFD: (491.71±41.03)mg/L vs (467.58±45.16)mg/L, (445.16±50.47)mg/L, P<0. 05]. Pearson correlation analysis showed that the serum level of CFB was positively correlated with glycosylated hemoglobin (HbA 1c), fasting plasma glucose (FPG) and TNF-α (all P<0.05) and negatively correlated with triiodothyronine (FT3) and total bilirubin (TBIL) (all P<0.05). Serum CFD level was positively correlated with systolic blood pressure, HbA 1c, FPG and TNF-α (all P<0.05), but negatively correlated with FT3 and TBIL (all P<0.05). Logistic regression analysis showed that CFB and CFD were still influential factors for the occurrence and development of DPN after excluding confounding factors such as systolic blood pressure, HbA 1c, FPG, FT3, DBIL, TBIL and TNF-α. Conclusions:(1) Serum CFB and CFD levels were significantly increased in DPN patients, suggesting that CFB and CFD may be involved in the occurrence and development of DPN. (2) Serum TNF-α level was significantly increased in DPN patients, confirming the role of TNF-α in the pathogenesis of DPN.
9.Eliminating Mother-to-Child Transmission of Syphilis: Chinese Practice before and during COVID-19 Pandemics
Du FANGZHI ; Zhang RUILI ; Wang QIANQIU
Chinese Medical Sciences Journal 2022;37(1):67-72
Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, World Health Orgernization launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100,000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are greatly challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, the remarkable achievements by the policy support under the leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19, adopting safe, rapid, early and high-quality clinical care for 100% of pregnant women to receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are the key measures to determine the effectiveness of MTCT for syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.
10.Neurosyphilis: current research status and management strategy exploration
Qianqiu WANG ; Fangzhi DU ; Xu ZHANG ; Ruili ZHANG
Chinese Journal of Dermatology 2021;54(11):951-954
Neurosyphilis is one of the most serious clinical manifestations of syphilis. In recent years, more and more neurosyphilis cases have been reported in Chinese literature. However, the exact incidence of neurosyphilis is unknown, and there are still some key scientific problems urgent to be solved in clinical diagnosis and treatment, pathogenesis, and prevention and control of neurosyphilis. Therefore, in order to provide a reference for the prevention and treatment of neurosyphilis, this article proposes the CARE-NS strategy, including the following 6 aspects: Comprehensive management including multiple disciplinary treatment (C) , Alleviating neurological impairment and sequelae (A) , Risk factors and clinical epidemiology (R) , Etiology and pathogenesis (E) , New diagnostic indicators and strategies (N) , Social impact and cost-effectiveness analysis (S) .

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