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.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.
3.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.
4.Management and operation of extra-large Fangcang hospitals: experience and lessons from containing the highly contagious SARS-CoV-2 Omicron in Shanghai, China.
Yun XIAN ; Chenhao YU ; Minjie CHEN ; Lin ZHANG ; Xinyi ZHENG ; Shijian LI ; Erzhen CHEN ; Zhongwan CHEN ; Weihua CHEN ; Chaoying WANG ; Qingrong XU ; Tao HAN ; Weidong YE ; Wenyi XU ; Xu ZHUANG ; Yu ZHENG ; Min CHEN ; Jun QIN ; Yu FENG ; Shun WEI ; Yiling FAN ; Zhiruo ZHANG ; Junhua ZHENG
Frontiers of Medicine 2023;17(1):165-171
5.Analysis and discussion on practical activities of standardized residency training in the department of radiology
Ming LIU ; Yuzhen ZHANG ; Xue′e CUI ; Shijian LI ; Dengbin WANG
Chinese Journal of Medical Education Research 2022;21(1):74-77
Based on the characteristics of medical imaging specialty, this paper introduces in detail several features of standardized residency training in the Department of Radiology in our hospital, from the aspects of teaching purpose, preliminary preparation and specific implementation, namely, the morning reading and analysis of difficult cases, the analysis of postoperative cases and missed diagnosis cases, and the teaching reading. At the same time, it also deeply analyzes the advantages, existing problems and solutions of this teaching practice. In order to provide reference for improving the teaching quality of the standardized residency training in the Department of Radiology.
6.Preliminary exploration of the relationship between the serum anti-Müllerian hormone and the related clinical factors
Chenhui LEI ; Kairu NI ; Lijuan WU ; Shijian YAN ; Hong ZHANG ; Yizhen SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(4):221-225
Objective:To explore the relationship between serum anti-Müllerian hormone (AMH) level and related clinical factors in healthy females, and establish and validate equation of correlation between age and serum AMH level for healthy females.Methods:From March 2015 to December 2016, a total of 602 females who measured serum AMH level in Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University were retrospectively enrolled. All cases had relatively complete clinical data, and were divided into healthy group (484 cases, 20-52 years) and case group (118 cases, 20-42 years; patients with menstrual disorders). Relationships between serum AMH level and estradiol (E2), tesosterone (T), follicle stimulating hormone (FSH), luetinizing hormone (LH), body mass index (BMI) of healthy group were analyzed by Spearman rank correlation. Kruskal-Wallis rank sum test was used to analyze the relationship between history of gestation and serum AMH level. Serum AMH level of health group was processed to establish predictive equation for serum AMH level. Internal ( n=27) and external ( n=37) validation group were chosen from healthy females with serum AMH level measured to validate the equation, and signed rank test was used to analyze the data. Difference between serum AMH level in case group and healthy group with corresponding age was explored by independent-sample t test. Results:Serum AMH levels were positively correlated with E2 and T ( rs values: 0.263, 0.334, both P<0.001), and negatively correlated with FSH, LH, BMI ( rs values: from -0.515 to -0.110, all P<0.005). Predictive equation was established as LogAMH=-1.208+ 0.1×age-0.000 042×age 3 ( R2=0.735, P<0.001). No statistically significant difference was found between real serum AMH levels and calculated serum AMH levels in the internal and external validation groups ( z values: -1.62 and -1.52, both P>0.05). Females in case group ( n=118) and control group ( n=446) were divided into two sub-groups respectively (<35 years and ≥35 years), and serum AMH levels of case group were lower than those of control group with corresponding age ( t values: 18.64, 11.70, both P<0.001). Conclusions:In healthy females, serum AMH level is related to some clinical data. The equation between serum AMH level and age established in the study may provide reference for clinical diagnosis and treatment.
7.On the rotation mode of standardized residency training of non-imaging professional residents in the department of radiology
Yuzhen ZHANG ; Huanhuan LIU ; Shijian LI ; Ming LIU ; Lingwei YU ; Dengbin WANG
Chinese Journal of Medical Education Research 2021;20(3):338-340
The department of radiology, as one of the public platforms for standardized residency training, is very crucial to the training of high level clinicians and essential to improve quality of medical care. According to the present situation and existing problems of standardized residency training for the non-imaging professional residents in the department of radiology in China, combining with our practice, this article primarily explores the improvement of the rules and regulations, the specific arrangement of the rotation, daily and graduation examination forms, and training quality supervision, etc. We hope to improve the training quality of the non-imaging professional residents' rotation in the department of radiology and explore more suitable and effective medical educative strategies.
8.Research of progress of pyruvate dehydrogenase complex in sepsis metabolism
Jie WU ; Weijin ZHANG ; Shucan ZHAO ; Jianqun LIN ; Shijian HU ; Liangfeng MAO ; Sheng AN
Chinese Critical Care Medicine 2021;33(6):765-768
Sepsis is a critical illness with high morbidity and mortality. Anaerobic glycolysis plays an important role in the pathogenesis of sepsis. Pyruvate dehydrogenase complex (PDHC) serves as a key regulator during sepsis. With PDHC dephosphorylation and deacetylation, PDHC activity is upregulated, allowing pyruvate translocate to mitochondria in aerobic condition, preceding the production of acetyl-CoA to accelerate aerobic oxidation. Activation of PDHC improves the prognosis of sepsis through regulating the balance of lactate, release of inflammatory factors and energy metabolism. A variety of remedies can improve the prognosis of patients with sepsis by up-regulating the activity of PDHC, including dichloroacetate (DCA), vitamin B1, milrinone, tumor necrosis factor binding protein, and ciprofloxacin.This article reviews the role and the regulatory mechanism of PDHC and signal pathway in the sepsis metabolism, in order to innovate treatment for sepsis and multiple organ dysfunction.
9.A primary study on application of the "Bi-system" iliac flap with simultaneous innervation in mandibular reconstruction
Xudong WANG ; Chengyao ZHANG ; Shijian ZHANG ; Jingcun SHI ; Ziqian WU ; Siyi LI ; Lei WANG
Chinese Journal of Plastic Surgery 2021;37(5):486-494
Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.
10.A primary study on application of the "Bi-system" iliac flap with simultaneous innervation in mandibular reconstruction
Xudong WANG ; Chengyao ZHANG ; Shijian ZHANG ; Jingcun SHI ; Ziqian WU ; Siyi LI ; Lei WANG
Chinese Journal of Plastic Surgery 2021;37(5):486-494
Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.

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