1.Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice
Changrui LONG ; Shijian XIANG ; Zhenhua ZHANG ; Huixing WU ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2025;36(6):668-673
OBJECTIVE To investigate the improvement mechanism of hyperoside (HYP) on non-alcoholic fatty liver disease (NAFLD). METHODS Male C57BL/6 mice were randomly divided into normal (NFD) group, model (HFD) group and HYP group, with 8 mice in each group. Except for NFD group, the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model; HYP group was simultaneously given HYP 100 mg/kg intragastrically every day, for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication; the histopathological changes and lipid accumulation in the liver were observed, and the contents of triglyceride (TAG) in liver tissue and serum contents of TAG, aspartate transaminase (AST) and alanine transaminase (ALT) were measured; LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis, and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α (PPARα) were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group, model group, HYP low-concentration group (50 μmol/L), HYP high-concentration group (100 μmol/L), HYP low-concentration+GW6471 (PPARαinhibitor) group, and HYP high-concentration+GW6471 group. Except for normal control group, the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed, and the TAG content was detected. RESULTS Compared with HFD group, HYP group exhibited significant reductions in liver fat vacuoles, lipid accumulation, liver weight, and TAG content in liver tissue, as well as serum contents of ALT, AST and TAG (P<0.05). Additionally, the expression of PPARα protein in liver tissue was significantly increased (P<0.05), and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG, diacylglycerol and other lipids in the liver. Compared with model group, cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups (P<0.05); GW6471 could significantly reverse the improvement effect of HYP on above indicators (P<0.05). CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice, and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.
2.Dynamic Sequential Diagnosis and Treatment of Pediatric Nephrotic Syndrome Based on the "Sweat Pore-Qi and Liquid-Kidney Collaterals"
Zhenhua YUAN ; Mingyang CAI ; Yingying JIANG ; Jingjing WU ; Wenqing PAN ; Zichao DING ; Shuzi ZHANG ; Xianqing REN
Journal of Traditional Chinese Medicine 2025;66(10):1007-1010
Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals", it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure, qi and liquid imbalance, and kidney collaterals impairment, and it is proposed that the treatment principle is to nourish the sweat pore, regulate qi and fluid, and supplement the kidney and unblock the collaterals. In clinic, guided by sequential therapy and according to the different disease mechanism characteristics of the four stages, including early stage of the disease, hormone induction stage, hormone reduction stage, hormone maintenance stage, the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency, modified Zhenwu Decoction (真武汤) was applied to warm yang and drain water; for hormone induction stage with yin deficiency resulting in effulgent fire, modified Zhibai Dihuang Pill (知柏地黄丸) plus Erzhi Pill (二至丸) was used to enrich yin and reduce fire; for hormone reduction stage with qi and yin deficiency, modified Shenqi Dihuang Decoction (参芪地黄汤) was used to boost qi and nourish yin; for hormone maintenance stage, modified Shenqi Pill (肾气丸) was used to supplement yin and yang. Meanwhile, the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals, so as to providing ideas for clinical treatment.
3.Study on chemical composition,pharmacodynamic consistency and mechanism between Hugan qingzhi formula decoction and its formulated granules
Zhenhua ZHANG ; Changrui LONG ; Huixing WU ; Shijian XIANG ; Benjie ZHOU
China Pharmacy 2025;36(12):1442-1448
OBJECTIVE To evaluate the contents of characteristic components in Hugan qingzhi formula (HGQZ) decoction and formulated granules and the pharmacodynamic consistency of them on high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) model mice, and explore their potential underlying mechanisms of action. METHODS Liquid chromatography-tandem mass spectrometry was used to analyze and compare the contents of six characteristic components in HGQZ decoction and formulated granules. Male C57BL/6 mice were randomly divided into normal control group, model group, HGQZ decoction low- dose and high-dose groups (13, 26 g/kg, calculated by crude drugs), and HGQZ formulated granules low-dose and high-dose groups (13, 26 g/kg, calculated by crude drugs), with 6 mice in each group. Except for the normal control group, which was fed a regular diet, the mice in the other groups were fed a high-fat diet for 20 weeks to establish the NAFLD model; at the same time, the mice in each group were gavaged with the corresponding drugs/water once. The fasting blood glucose (FBG) levels, glucose and insulin tolerance, body weight, liver index, white adipose Δ 基金项目 国家自然科学基金项目(No.82074078);广东省基础 tissue index, brown adipose tissue index, as well as lipid levels (total cholesterol, triglycerides) and liver function indicators (aspartate transaminase, alanine transaminase) were measured. Additionally, histopathological changes and lipid accumulation in liver tissues were observed. The serum samples of mice in the model group, HGQZ decoction high-dose group and HGQZ formulated granules high-dose group were taken for metabolomics analysis, and validation of the underlying mechanisms was conducted. RESULTS There were no statistically significant differences in the contents of ginsenoside Rb1, typhaneoside, isorhamnetin-3-O-neohesperidoside, hyperoside, nuciferine, and 23-acetylalismol B between HGQZ decoction and HGQZ formulated granules (P>0.05). Compared with the model group, the hepatic histopathological changes in mice were alleviated in both the HGQZ decoction group and all dose groups of HGQZ formulated granules. Inflammatory cell infiltration and lipid vacuoles were reduced. Additionally, there was a general improvement in FBG levels, glucose tolerance, insulin tolerance, body weight, liver index, white/brown adipose tissue index, lipid levels, and liver function indicators (P<0.05). However, no statistically significant differences were observed between these treatment groups (P>0.05). There were 234 and 136 differentially expressed serum metabolites identified in the model group versus HGQZ decoction high-dose group, and model group versus HGQZ formulated granules high-dose group, respectively. After taking the intersection, 65 common differentially expressed metabolites were obtained, which were enriched in metabolic pathways such as purine metabolism and tricarboxylic acid cycle metabolism. Among these, the content of citrate in the model group was significantly lower than that in both the HGQZ decoction group and HGQZ formulated granules high-dose group (P<0.05). Both high-dose HGQZ decoction and formulated granules could significantly elevate the phosphorylation levels of AMP-activated protein kinase (AMPK) (P<0.05). CONCLUSIONS HGQZ decoction and formulated granules contain comparable amounts of characteristic components, and both exhibit equivalent efficacy on NAFLD model mice. The anti-NAFLD effects of HGQZ are associated with the activation of the AMPK energy metabolism pathway.
4.Measurement and analysis of radiation doses received by the human body and radiation levels in the CT room under digital miniature CT scanning conditions
Lin YIN ; Zhenhua YANG ; Yaqi XI ; Wenlong FAN ; Rui YANG ; Qisheng XIA ; Qiaoling WU
Chinese Journal of Radiological Health 2025;34(3):373-377
Objective To evaluate the radiation impact of a self-developed digital miniature CT on the human body and the environment under simulated scanning conditions, and verify its safety and regulatory compliance. Methods Under typical head scanning conditions with the digital miniature CT (70 kV/10 mA), the equivalent doses received at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads of the phantom were measured without protection and with 0.5 mmPb equivalent protection using LiF (Mg, Cu, P) thermoluminescent dosimeters. The ambient dose equivalent rates at the bed level inside the CT room at different directions and distances from the scanning center were measured using a model AT1121 X/γ dosimeter. The equivalent doses of organs on both sides of the phantom and the ambient equivalent dose rates on the left and right sides of the longitudinal axis of the bed in the CT room were compared. The Mann-Whitney test was used at a significance level of P < 0.05. Results During a single scan of the head with the digital miniature CT, the equivalent doses at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads without protection were 1.04, 0.95, 0.55, 0.57, 0.40, and 0.12 mSv, respectively, which were only 0.84% to 8.24% of the doses inside the irradiation field. With 0.5 mm Pb equivalent protection, the equivalent dose of the thyroid decreased from 8.24 mSv to 3.27 mSv with a reduction of 60.3%, and the doses of the other organs were reduced to 1.5-11.5 μSv with the maximum reduction of 14 times. In the longitudinal axis direction of the CT bed, the ambient dose equivalent rate at a distance of 2 m from the scanning center was reduced to 0.066 mSv/h, which was only 9.6% of the ambient equivalent dose rate at a distance of 50 cm from the scanning center. Conclusion The digital miniature CT has advantages in ensuring patient safety, optimizing imaging quality, and promoting technological development, demonstrating promising application potential. However, the radiation protection of personal and CT room should not be ignored.
5.Epidemiological characteristics of patients with severe fever with thrombocytopenia syndrome in Dongyang City
CHEN Kang ; WU Ailan ; MA Jingjing ; WU Zhenhua ; XU Yuechen ; ZHANG Jing ; JIN Xujing ; CAO Hui ; CHEN Shuang
Journal of Preventive Medicine 2024;36(1):47-50
Objective :
To investigate the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Dongyang City, Zhejiang Province from 2017 to 2022, so as to provide insights into SFTS prevention and control.
Methods:
Data pertaining to patients with SFTS in Dongyang City from 2017 to 2022 were collected from Notifiable Infectious Disease Reporting System of Chinese Disease Prevention and Control Information System. The epidemiological and clinical characteristics of patients with SFTS were descriptively analyzed, and the trends in incidence of SFTS was evaluated using annual percent change (APC).
Results:
A total of 32 SFTS cases were reported in Dongyang City from 2017 to 2022, with mean annual incidence of 0.63/105, and 8 cases died, with a fatality rate of 25.00%. The incidence of SFTS appeared a tendency towards a rise from 2017 to 2022 (APC=40.697%, P<0.05). The male to female ratio of SFTS cases was 0.78∶1, and farmer was the predominant occupation (31 cases, 96.88%). SFTS predominantly occurred among individuals at ages of 51 to 69 years (20 cases, 62.50%), and the incidence peaked during the period between March and May and between July and August (28 cases, 87.50%). SFTS cases were reported in 11 out of the 18 townships (streets) in Dongyang City, with the highest number found in Zuocun Township (8 cases, 28.13%), and had the lowest platelet count of (41.46±5.19)×109 platelets/L, with the lowest count of (3.00 to 67.00) ×109 platelets/L. All the SFTS cases had a history of mountain forest and farmland activities 2 weeks prior to onset of the disease, and 5 cases (15.63%) had a history of tick bites.
Conclusions
The incidence of SFTS appeared a tendency towards a rise in Dongyang City from 2017 to 2022, and SFTS was highly prevalent in spring and summer, with high incidence among farmers. Intensified health education of SFTS is recommended among residents in high-incidence areas.
6.Efficacy of low-dose inhaled nitric oxide in the treatment of severe hypoxemia after Sun’soperation: A retrospective cohort study
Xiaozhong MA ; Shaopeng ZHANG ; Yunpeng BAI ; Zhenhua WU ; Feng ZHAO ; Qingliang CHEN ; Nan JIANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):762-767
Objective To investigate the efficacy of low-dose inhaled nitric oxide (iNO) in the treatment of severe hypoxemia after Sun’s operation. Methods The clinical data of patients undergoing Sun’s operation for acute Type A aortic dissection in our hospital from January 2020 to June 2022 were retrospectively analyzed. Patients who received conventional treatment before November 2021 were enrolled as a control group. After November 2021, iNO was used in our hospital, and the patients who received iNO as an iNO group. The preoperative clinical baseline data, perioperative clinical data and oxygenation index were compared between the two groups. Results A total of 54 patients were included in the control group, including 45 males and 9 females, with an average age of 53.0±10.9 years. A total of 27 patients were included in the iNO group, including 21 males and 6 females, with an average age of 52.0±10.6 years. The preoperative body mass index of the two groups was greater than 25 kg/m2, white blood cell count, C-reactive protein were significantly higher than normal level, but there was no statistical difference between the groups (P>0.05). There were no statistical differences in intraoperative data between the two groups (P>0.05). The iNO group had significantly shorter duration of mechanical ventilation, postoperative ICU stay, and postoperative hospital stay than the control group (P<0.001). After 12 h of iNO treatment, hypoxic condition improved obviously, oxygenation indices in 12 h, 24 h, 36 h,48 h, 60 h and 72 h in the iNO group were significantly higher than those in the control group (P<0.05). Conclusion The treatment of severe hypoxemia after Sun’s surgery with low-dose of iNO is safe and effective, can significantly improve oxygenation function, and has significant advantages in shortening ventilator use time, postoperative ICU stay and postoperative hospital stay, but it is not significant in changing postoperative mortality.
7.Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy
Meifang REN ; Zhenhua WU ; Fei GAO ; Guodong YUAN ; Qian ZHANG ; Xiaoling GUO ; Fengwen YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):55-62
ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum (ER) stress and reducing urinary protein in the rat model of diabetic nephropathy (DN). MethodSeventy-five SD rats were randomized into normal, model, low-, medium-, and high-dose (4.37, 8.73, 17.46 g·kg-1, respectively) modified Shengjiangsan, and irbesartan (0.014 g·kg-1) groups, with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage, once a day, for 8 consecutive weeks. After the last administration, the levels of glucose (GLU) in the blood, 24-hour urinary protein (24 h-UTP), and superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the renal tissue were measured. Hematoxylin-eosin staining, periodic acid-Schiff staining, and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin, podocin, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and activating transcription factor 4 (ATF4) in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 (Sirt1), phosphorylated (p)-protein kinase RNA-like endoplasmic reticulum kinase (PERK), and p-eukaryotic translation initiation factor 2 alpha (eIF2α) in rat kidneys. ResultCompared with the normal group, the modeling caused pathological damage to the kidneys, elevated the levels of GLU and 24 h-UTP (P<0.05), up-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and down-regulated the protein level of Sirt1 (P<0.05) in rat kidneys. Compared with the model group, modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels (P<0.05), alleviated the pathological damage in the renal tissue, down-regulated the protein levels of GRP78, CHOP, ATF4, p-PERK, and p-eIF2α (P<0.05), and up-regulated the protein level of Sirt1 (P<0.05). ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue, thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.
8.Serum metabolomics-based study on the mechanism of action of bergapten in the treatment of liver fibrosis
Huixing WU ; Zhenhua ZHANG ; Changrui LONG ; Guifen GUO ; Yanyu WANG ; Yanchun CHEN ; Juxiong FU ; Shijian XIANG ; Benjie ZHOU ; Chengyu LU
China Pharmacy 2024;35(13):1570-1575
OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group (0.5% carboxymethyl cellulose sodium solution), model group (0.5% carboxymethyl cellulose sodium solution), and BP low-dose and high-dose groups (50, 100 mg/kg), with 10 mice in each group. Except for the normal control group, the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model; they were given relevant medicine/solution intragastrically, once a day, for consecutive 8 weeks. After the last medication, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were detected, and liver pathological changes were observed; the expressions of α-smooth muscle actin (α-SMA) and Collagen Ⅰ were detected in liver tissue; the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group, serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups (P<0.05), while liver fibrosis was improved significantly. Meanwhile, metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group, of which 18 substances were upregulated and 157 substances were downregulated; the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism, butanoate metabolism, fatty acid synthesis, tyrosine metabolism, β-alanine metabolism, nicotinic acid and nicotinamide metabolism, glutathione metabolism, etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism, butanoate metabolism, glutathione metabolism and so on in rats with liver fibrosis.
9.Development and current status of multidisciplinary diagnosis and treatment model in hepato-pancreato-biliary diseases
Xiaoyin YUAN ; Chao WANG ; Zhengwei HE ; Xuewei JIANG ; Chengxian WU ; Runhu LAN ; Ling GUO ; Awang DANZENG ; Pingcuo CIREN ; Zhenhua YANG ; Binhao ZHANG
Chinese Journal of Hepatobiliary Surgery 2024;30(3):224-228
Hepato-pancreato-biliary diseases (HPBD) are often complicated. The diagnosis and treatment of HPBD involve many disciplines. The malignant degree of hepatobiliary pancreatic system is high, and the prognosis of patients is poor. The multidisciplinary team (MDT) brings specialists from different disciplines together to make a comprehensive and individualized treatment for patients. MDT is emerging in HPBD in recent years. MDT helps improve the accuracy of diagnosis and prognosis. However, there are still some controversies and obstacles in the application of MDT for patients with HPBD. We reviewed the development, current status and experience of MDT in the field of HPBD, analyze the current controversy and obstacles, and providing reference for its future application.
10.Rougan Huaxian Particle Regulates Mitophagy via miR-135a/FOXO1 Pathway to Inhibit the Progression of Liver Fibrosis in Rats
Huixia LAO ; Shanshan WU ; Zhenchang WANG ; Jing WANG ; Zhenhua HUANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):957-964
Objective To investigate the effect and mechanism of Rougan Huaxian particle on hepatic fibrosis.Methods SD rats were divided into normal group,model group,normal saline control group,Rougan Huaxian particle low,middle,high dose group,Rougan Huaxian particle middle dose+3-MA group.Liver fibrosis model was induced by intraperitoneal injection of CCl4.Rougan Huaxian particle was administered with low,middle and high dose(2.5 mg·kg-1,5 mg·kg-1,10 mg·kg-1)and 3-MA(15 mg·kg-1)respectively.The expression of miR-135a,FOXO1,PINK1,Parkin,LC3 II,Smad2,p-Smad2,TGF-β1,NF-κB p65,p-NF-κB p65,α-SMA,Collagen I,Collagen III,TNF-α and the content of ROS were detected by Real-time PCR,Western Blot and ELISA.Results The expression of miR-135a,α-SMA,Collagen I,Collagen III,p-Smad2,TGF-β1,p-NF-κB p65,TNF-α and ROS in model group were significantly up-regulated(P<0.05),and the expression of FOXO1,PINK1,Parkin,LC3 II were significantly down-regulated(P<0.05).The middle and high dose of Rougan Huaxian particle could significantly inhibit the expression of miR-135a,α-SMA,Collagen I,Collagen III,p-Smad2,TGF-β1,p-NF-κb p65,TNF-α and ROS,and up-regulate the expression of FOXO1,PINK1,Parkin,LC3 II(P<0.05).The expression of miR-135a,α-SMA,Collagen Ⅰ,Collagen Ⅲ,p-Smad2,TGF-β1,p-NF-κB p65 and TNF-α and the production of ROS were significantly inhibited in the medium and high dose groups.Up-regulated expression of FOXO1,PINK1,Parkin and LC3Ⅱ(P<0.05).The effect of Rougan Huaxian Particle in middle dose group was stronger than that in low dose group(P<0.05),and there was no significant difference between middle and high dose groups.Mitophagy inhibitor(3-MA)could significantly inhibit the efficacy of rougan Huaxian particle(P<0.05).Conclusion Ruugan Huaxian granules can inhibit liver fibrosis,and its mechanism is related to the inhibition of miR-135a expression,activation of FOXO1/PINK1 pathway,promotion of mitochondrial autophagy,inhibition of oxidative stress response,and inhibition of TGF-β1/Smad2 activation.


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