1.Mechanism of Zishen Qinggan Prescription in Improving Glucose and Lipid Metabolism in Type 2 Diabetes Based on Transcriptomics
Jingcun WANG ; Chunyu TIAN ; Fan ZHANG ; Xiaojin LA ; Fanwu WU ; Liang ZHU ; Leilei MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):109-117
ObjectiveBased on network pharmacology and transcriptomics, the mechanism of Zishen Qinggan prescription (ZSQGF) in improving glucose and lipid metabolism in type 2 diabetes (T2DM) model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM, gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG) analysis were conducted, and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin (STZ). The rats were randomly divided into the control group, model group, metformin (Met, 72 mg·kg-1) group, and ZSQGF high-, medium-, and low-dose groups (ZSQGF-H, ZSQGF-M, and ZSQGF-L, with 4.8, 2.4, and 1.2 g·kg-1 raw drug in the solution). The living status of rats was monitored and the levels of total cholesterol (TC), total triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin(HE) staining and oil red O staining. The differential genes were analyzed through transcriptomics, GO and KEGG analysis, and the protein-protein interaction(PPI) network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results, the protein pathways were identified. The expression levels of nuclear factor-κB (NF-κB), matrix metalloproteinase(MMP)-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2(Bcl-2) modifying factor(BMF), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4), and fatty acid synthase(FASN) was detected by real-time polymerase chain reaction(Real-time PCR). The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration, the body weight, blood sugar, serum indicators, and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB, MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF, NOX4, and FASN in the ZSQGF-H group, while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN, reducing lipid synthesis, and regulating the NF-κB signaling pathway.
2.Effect of apoptosis inhibitor of macrophage in inflammatory reactions and lipid metabolic diseases
Fan ZHANG ; Chunyu TIAN ; Jingcun WANG ; Xiaojin LA ; Qianru FU ; Jie LI ; Wenhao FU
Chinese Journal of Comparative Medicine 2024;34(3):142-148
Apoptosis inhibitor of macrophage(AIM)belongs to group B of the scavenger receptor cysteine rich-super family.AIM is a soluble protein secreted by macrophages.The expression of this protein is controlled by the liver X receptor.AIM,which is secreted by macrophages,plays important and broad roles in the immune responses of the body.It not only inhibits the apoptosis of macrophages but also participates in the regulation of macrophage polarization.In addition,studies have revealed that AIM is involved in various physiological and pathological processes,such as inflammation,obesity,atherosclerosis,and cancer.It has been used as a biological marker for the diagnosis of diseases such as tuberculosis and liver cirrhosis.Moreover,it can promote the lipolysis of adipose cells by inhibiting the activity of fatty acid synthase(FAS),playing an important role in the regulation of lipid homeostasis,lipid metabolism,and autoimmune diseases.In this paper,we review the multiple functional characteristics of AIM and its effects on inflammation,lipid metabolism,and related diseases to provide a theoretical basis for relevant medical research.
3.Regulation of Suaeda salsa in renal AIM and macrophage polarization in rats with diabetes kidney disease
Fan ZHANG ; Chunyu TIAN ; Jingcun WANG ; Xiaojin LA ; Liang ZHU ; Hong CHANG ; Biwei ZHANG ; Ji'an LI
International Journal of Traditional Chinese Medicine 2024;46(9):1155-1162
Objective:To explore the regulatory effect of Suaeda salsa on renal apoprosis inhibitor of macrophage (AIM) and macrophage polarization in diabetes kidney disease (DKD) model rats.Methods:A DKD rat model was established using a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). The rats were divided into model group, metformin group, and Suaeda salsa high-, medium-, and low-dosage groups using a random number table method, with 8 mice in each group. The normal group was set with 8 rats in this group. The metformin group was given 85.71 mg/kg of metformin solution by gavage, while the Suaeda salsa high-, medium-, and low-dosage groups were given 3.08, 1.54, and 0.77 g/kg of Suaeda salsa suspension by gavage (raw dosage). The normal group and model group were given equal volumes of saline by gavage, once a day, administered by gavage for 12 weeks of intervention. Fasting blood glucose (FBG) and glucose tolerance (OGTT) were measured, and the area under the curve (AUC) was calculated; the levels of glycosylated hemoglobin (HbA1c) and glycosylated serum protein (GSP) were detected; urea nitrogen (BUN), serum creatinine (SCr), and 24-hour urine protein (24 hUP) were detected; HE staining was used to observe the pathological morphology of the kidneys; Masson and PAS staining were used to observe renal tissue fibrosis; Western blot method was used for detecting AIM, CD206, CD86, TNF-α and IL-10 protein levels in renal tissue; Immunofluorescence was used to detect the average optical density values of AIM, CD206, and CD86 proteins in renal tissue.Results:Compared with the model group, the FBG, OGTT AUC, HbA1c, GSP of each dosage group of Suaeda salsa decreased ( P<0.01); the expression levels of AIM, CD206, and IL-10 proteins in renal tissue increased ( P<0.01 or P<0.05), while the expression levels of CD86 and TNF-α protein significantly decreased ( P<0.01 or P<0.05); HE, Masson, and PAS staining results showed that compared with the model group, the changes in renal microvasculature and renal fibrosis of rats in each dosage group of Suaeda salsa were improved. Conclusion:Suaeda salsa may regulate AIM, promote polarization of M2 macrophages, improve the inflammatory microenvironment of macrophages, thereby lowering blood lipids of DKD rats, and improving renal pathological damage.
4.Application of percutaneous transhepatic gallbladder drainage with delayed laparoscopic cholecystectomy in the treatment of acute cholecystitis
Fang WANG ; Jiajia SHEN ; Jingxiong HE ; Fan PAN ; Xiaojin ZHANG
International Journal of Surgery 2023;50(8):514-519
Objective:To compare the clinical efficacy of percutaneous transhepatic gallbladder drainage (PTGBD) combined with delayed laparoscopic cholecystectomy (LC) with direct LC in the treatment of acute cholecystitis.Methods:A single-center case-control retrospective study was used. Sixty-three patients with acute cholecystitis with onset time ≥ 72 hours during the period from August 1, 2021 to December 10, 2022 in the Department of Hepatobiliary Surgery of the 900TH Hospital of Joint Logistics Support Force were selected. There were 38 males and 25 females, aged (57.3±15.4) years, with an age range of 28-87 years. According to whether PTGBD treatment was performed before LC, they were divided into experimental group ( n=29) and control group ( n=34). Experimental group was treated with PTGBD combined with delayed LC and control group was treated with LC only.The differences in operative time, intra-operative bleeding, intra-operative transit open rate, post-operative hospital days, total hospital days, hospital costs, short-term post-operative complications of LC and post-operative time to exhaustion were compared and analysed between the two groups. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and independent sample t-test was used for comparison between groups.Measurement data with skewed distribution were expressed as M( Q1, Q3), and rank sum test was used for comparison between groups; Chi-square test was used to compare the counting data groups. Results:Intraoperative bleeding, total hospital days, hospital costs and postoperative time to exhaustion were 0(0, 50) mL, 13(11, 18) d, 29 015.0 (22 791.6, 39 000.8) yuan and 1(1, 2) d in the experimental group and 50(0, 88) mL, 7(6, 11) d, 16 015.0 (15 832.1, 22 185.1) yuan, 2(1, 3) d, the difference was statistically significant between the two groups( P<0.05). In the experimental group, the operative time, the intraoperative transit open rate, the number of postoperative hospital days, and the incidence of short-term postoperative complications of LC were 80 (55, 115) min, 13.8%, 5 (3, 7) days, 34.5%, respectively, compared with 98(70, 125) min, 20.6%, 5(3, 6) days, 38.2% in the control group, the difference between the two groups was not statistically significant ( P>0.05). Conclusion:The clinical efficacy of PTGBD combined with delayed LC is better than direct line LC, and it is feasible and effective for patients with cholecystitis whose inflammatory indexes have returned to normal and who have high gallbladder tone.
5. Short-term efficacy evaluation of laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy
Yunfei ZHANG ; Peng CHEN ; Jiangang SUN ; Xiaojin FAN ; Yiming WANG ; Yongshun GAO
Chinese Journal of Gastrointestinal Surgery 2020;23(2):177-182
Objective:
To investigate short-term efficacy of laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy.
Methods:
A case series study was carried out. Case inclusion criteria: (1) patient was confirmed as gastric adenocarcinoma by gastroscopic biopsy before operation; (2) locally advanced gastric cancer was confirmed by abdominal CT before operation; (3) no distant metastases such as liver, lung, and posterior peritoneal lymph nodes, and no tumor directly invading the pancreas, spleen, liver, and colon were verified by superficial lymph node ultrasound, chest and abdominal CT before operation;(4) total gastrectomy or proximal gastrectomy plus D2 lymphadenectomy were performed, and R0 resection was confirmed by postoperative pathology. Exclusion criteria: (1) intraperitoneal dissemination or distant metastasis was found during laparoscopic exploration; (2) No.10 lymph nodes were significantly enlarged or fused into clusters; (3) pathological diagnostic data were incomplete. According to above criteria, the clinicopathological data of 36 patients who underwent laparoscopic spleen-preserving No.10 lymphadenectomy and left epigastrium mesogastric excision based on interspace anatomy for advanced proximal gastric cancer in The First Affiliated Hospital of Zhengzhou University from June 2017 to March 2018 were retrospectively collected and analyzed. The intraoperative conditions, postoperative recovery and complications of patients were analyzed.
Results:
In 36 patients, the mean age was (59.8±8.0) years, the mean BMI was (23.9±3.5) kg/m2, and 8 cases (22.2%) received preoperative chemotherapy. All the patients underwent successfully the laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision. In the examination of postoperative resected specimens, it was found that the mesangial boundary of the upper and posterior part of the stomach was smooth, indicating the efficiency of complete mesangial resection. No case was converted to open operation. The mean time of lymph node dissection and mesangial resection was (34.2±11.4) minutes. The mean blood loss during operation was (44.8±21.3) ml. The mean number of lymph node dissection per patient was 45.6±17.6. The mean number of No. 11p+11d lymph node dissection was 3.1± 2.8 per patient, and 7 patients were pathologically positive with metastasis rate of 19.4% (7/36). The mean number of No.10 lymph node dissection was 2.9±2.5 per patient, and 2 patients were pathologically positive with metastasis rate of 5.6% (2/36). The time to postoperative flatus was (3.8±0.6) days, time to removal of nasogastric was (1.9±0.7) days, time to the first intake of fluid was (3.0±0.4) days, time to removal of drainage tube was (6.0±1.2) days. Postoperative mean hospital stay was (12.8±4.0) days. One case (2.7%) developed pulmonary embolism and 1 case (2.7%) developed gastroplegia after operation. The morbidity of postoperative complication was 5.6% (2/36). No operative site infection, postoperative bleeding and death within postoperative 30-day were observed. All the 36 patients were followed up and the median follow-up was 18 months (12-28 months). Seven patients died of tumor relapse and metastasis (3 cases died within postoperative 1 year) and another 1 case developed colonic cancer 17 months after operation.
Conclusion
Laparoscopic spleen-preserving splenic hilus lymphadenectomy and left epigastrium mesogastric excision for advanced proximal gastric cancer based on mesangial anatomy is safe and feasible.
6.Correlation between the elevation of D-dimer and of deep venous thrombosis progression of the lower extremities after abdominal surgery
Yongshun GAO ; Xizhong YAN ; Jingjing HUANG ; Peng CHEN ; Yunfei ZHANG ; Xiaojin FAN ; Jiangang SUN ; Yiming WANG
Chinese Journal of General Surgery 2017;32(12):1022-1025
Objective To investigate the value of D-dimer in predicting the progression of lower extremity deep venous thrombosis (DVT) during perioperative period of gastrointestinal surgery.Methods Color Doppler ultrasound was used to dynamically monitor the formation and changes of perioperative deep venous thrombosis (DVT) in 239 patients receiving abdominal surgery in our department from Nov 2014 to Aug 2016.Changes of plasma D-dimer were measured,and clinical data of malignant tumor,infection,age,BMI were collected.The relationship between D-dimer elevation and DVT progression was analyzed.Results Lower extremity DVT after surgery developed in 97 patients,and thrombosis progression occurred in 16.6% (16/97).Univariate logistic regression analysis showed that continuous increase of postoperative D-dimer was closely related to the progression of thrombosiss.Multivariate Logistic regression analysis showed that the continuous rise of D-dimer was an independent risk factor for thrombosis.ROC curve analysis showed significantly increased risk of thrombosis progression,when plasma D-dimer polymerization increased >0.87 mg/L on the 3rd day.Conclusion The continuous increase of D-dimer > 0.87 mg/L predicts DVT progression of lower extremity DVT.
7.Clinical significance of FOXM1 and Gli-1 protein expression in high-grade ovarian serous carcinoma
Jun ZHANG ; Zhiyan LI ; Xiaojin DUAN ; Xiaomei FAN ; Weina LIU ; Yuehong LI
Chinese Journal of Oncology 2016;38(12):904-908
Objective To investigate the different expression and prognostic significance of forkhead box M1 ( FOXM1) and Gli?l in ovarian high grade serous carcinoma ( HGSC) . Methods The expressions of FOXM1 and Gli?1 in 94 cases of HGSC and 20 cases of normal fallopian tube tissues were detected by immunohistochemistry. Kaplan?Meier analysis and Cox multivariate survival analysis were used to assess the relationship of the FOXM1 and Gli?1 levels with age, International Federation of Gynecology and Obstetrics ( FIGO) stage, omental metastasis, and residual foci and prognosis of HGSC. Results The positive rates of FOXM1 and Gli?1 expression in HGSC were 79.8% (75/94) and 77.7% (73/94), respectively, both significantly higher than those of the normal controls ( P<0.05) . The expressions of FOXM1 and Gli?1 were significantly correlated with FIGO stage, and both of their positive rates in stage Ⅲ-Ⅳpatients were significantly higher than those in stage Ⅰ-Ⅱ cases ( P<0.001) . The expressions of FOXM1 in HGSC were positively correlated with Gli?1. Kaplan?Meier analysis revealed that the 5?year overall survival rates of FOXM1?and Gli?1?positive groups were 8.0% and 6.8%, significantly lower than 36.8% and 38.1% of the FOXM1?and Gli?1?negative groups, respectively ( P<0. 05 for both ) . Cox multivariate survival analysis revealed that FIGO stage and overexpression of FOXM1 protein were independent prognostic factors of HGSC patients ( P<0.05 for both) . Conclusions The overexpression of FOXM1 and Gli?1 proteins participate in the carcinogenesis of HGSC, and are significantly associated with FIGO stage. The protein expression of FOXM1 is positively correlated with Gli?1 in HGSC. Expression of FOXM1 protein and FIGO stage are independent prognostic factors of HGSC.
8.Clinical significance of FOXM1 and Gli-1 protein expression in high-grade ovarian serous carcinoma
Jun ZHANG ; Zhiyan LI ; Xiaojin DUAN ; Xiaomei FAN ; Weina LIU ; Yuehong LI
Chinese Journal of Oncology 2016;38(12):904-908
Objective To investigate the different expression and prognostic significance of forkhead box M1 ( FOXM1) and Gli?l in ovarian high grade serous carcinoma ( HGSC) . Methods The expressions of FOXM1 and Gli?1 in 94 cases of HGSC and 20 cases of normal fallopian tube tissues were detected by immunohistochemistry. Kaplan?Meier analysis and Cox multivariate survival analysis were used to assess the relationship of the FOXM1 and Gli?1 levels with age, International Federation of Gynecology and Obstetrics ( FIGO) stage, omental metastasis, and residual foci and prognosis of HGSC. Results The positive rates of FOXM1 and Gli?1 expression in HGSC were 79.8% (75/94) and 77.7% (73/94), respectively, both significantly higher than those of the normal controls ( P<0.05) . The expressions of FOXM1 and Gli?1 were significantly correlated with FIGO stage, and both of their positive rates in stage Ⅲ-Ⅳpatients were significantly higher than those in stage Ⅰ-Ⅱ cases ( P<0.001) . The expressions of FOXM1 in HGSC were positively correlated with Gli?1. Kaplan?Meier analysis revealed that the 5?year overall survival rates of FOXM1?and Gli?1?positive groups were 8.0% and 6.8%, significantly lower than 36.8% and 38.1% of the FOXM1?and Gli?1?negative groups, respectively ( P<0. 05 for both ) . Cox multivariate survival analysis revealed that FIGO stage and overexpression of FOXM1 protein were independent prognostic factors of HGSC patients ( P<0.05 for both) . Conclusions The overexpression of FOXM1 and Gli?1 proteins participate in the carcinogenesis of HGSC, and are significantly associated with FIGO stage. The protein expression of FOXM1 is positively correlated with Gli?1 in HGSC. Expression of FOXM1 protein and FIGO stage are independent prognostic factors of HGSC.
9.Comparison on Pomegranate Leaf Tennis andAnanas coumosus Leaf Phenols on Growth of Lactation Mice
Xinpei WANG ; Dongming XING ; Jingfei JIANG ; Xuan YU ; Xiaojin YAN ; Fan LEI ; Lijun DU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;17(3):526-530
This study was aimed to observe the effect ofpomegranate leaf tennis and Ananas coumosus leaf phenols on the growth of lactating mice through breast milk. Intragastric administration of different doses of drug was given to maternal mice. The general condition of newborn mice, body weight, tail length and organ coefficient of liver-related factors regulating the expression of lipid metabolism were observed. The results showed that both pomegranate leaf tennis and A. coumosus leaf phenols can obviously affect the growth and development of newborn mice through breast milk. And the effect of pomegranate leaf tennis was stronger than A. coumosus leaf phenols. Meanwhile, it obviously downregulated the expression of liver-related lipid metabolism enzymes in newborn mice. It was concluded that pomegranate leaf tennis and A. coumosus leaf phenols can affect the growth and development of newborn mice through breast milk. Its effect was related to the influence of lipid metabolism enzyme in the liver. Attention should be paid on taking this medication during lactation. Its clinical significance still required in-depth study.
10.Diagnosis and treatment of grade Ⅴ liver trauma combined with hilar bile duct transection injury
Jiajia SHEN ; Fan PAN ; Xiaojin ZHANG ; Shaohua CHEN ; Yi JIANG
Chinese Journal of Digestive Surgery 2015;14(4):349-351
According to the Organ Injury Scale Grading System of the American Association for the Surgery of Trauma (AAST-OIS),grade Ⅴ liver trauma is always complicated with retrohepatic inferior vena cava injury and less bile duct injury,and it is extremely severe and difficult to be treated.Timely and fast judgment,emergent exploration and effective repair of the injured bile duct are the key points for the treatment of bile duct injury.One patient with grade Ⅴ liver trauma combined with hilar bile duct transection injury was admitted to the Fuzhou General Hospital of Nanjing Military Command on August 30,2013.The rupture of left and right liver junction was detected by preoperative multidisciplinary consultation and emergency open surgery at admission hour 4.There was left and right hepatic duct bifurcation rupture at the first hepatic hilum.Non-functional liver tissues were excised.Breakage left and middle hepatic vein were sutured by polymer suture line.Liver traumatic bleeding and bile duct were sutured and ligatured individually.Left and right hepatic duct laceration was sutured by 6-0 PDS suture line.A hole in the stomach wall was opened fist,and then most part of the gastric contents was removed and the gastric wall was reparied by stapler.Patient received the postoperative symptomatic treatment with gradual recovery,and was discharged from hospital at admission day 26.The patient was readmitted to the hospital at 31 days of discharge due to outflow of purulent fluid from abdominal cavity drainage tube,and was treated by ceftriaxone sodium and tazobactam sodium according to the results of drug sensitive test and continuous peritoneal lavage.The abdominal cavity drainage tube and left and right hepatic duct drainage tube were removed at postoperative day 83.The patient was discharged from hospital at readmission day 28,and was followed up till December 2014 with good recovery and without complication.

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