Objective To compare prospectively the features and effects of combined operation(splenorenal shunt plus portal-azygous devascularization) and portal-azygous devascularization only(PCDV)on portal(hypertension)(PH).Methods We summarized 360 cases of PH admitted from 1984 to 2004.All patients were randomly divided into two groups,one was combined operative group(250 patients) and the other was PCDV group(110 patients).The therapeutic effects and changes of portal hemodynamics were studied with doppler flowmeter(DCFI),free portal pressure(FPP) and digital subtraction angiography(DSA) pre-and post-operatively,and were measured directly during the course of the procedure.Results(1)Postoperative bleeding:Of all the patients who underwent combined operation,no case of rebleeding occurred in the short period after operation,and the rebleeding rate was 8.0% in the long period of follow-up.In the patients who underwent PCDV,the rebleeding rate was 5.5% in the short period after operation,and 17.6% at long-term follow up(P0.05).(3)There was a significant decrease in the diameter of portal vein,and FPP postoperatively in the combined operation group compared to PCDV group.There was a significant decreases of PVF in the PCDV group.But the decrease of PVF in the two groups had no significant difference.Conclusions The combined procedure has merits of greater decrease of FPP,and alleviation of the condition of hyperdynamic blood flow in the portal vein.The clinical effect is also better than that of portal-azygous devascularization only.

ObjectiveTo explore the effects and mechanisms of modified Dahuang Huanglian Xiexintang on hepatic oxidative stress injury in type 2 diabetes mellitus （T2DM） rats based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） axis. MethodSix ZDF （fa/+） rats were as assigned to the blank group， and 30 ZDF （fa/fa） rats were used to induce the T2DM model by feeding a high-fat diet. After successful modeling， the rats were randomly divided into the model group， metformin group （0.18 g·kg^-1）， and low， medium， and high dose groups of modified Dahuang Huanglian Xiexintang （0.54， 1.08， 2.16 g·kg^-1）， with six rats in each group. After 12 weeks of drug intervention， the body mass， liver mass， fasting blood glucose （FBG）， and oral glucose tolerance test （OGTT） levels were measured. Serum total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL）， low-density lipoprotein cholesterol （LDL）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） levels were detected using an automatic biochemical analyzer. The pathological changes of liver tissue were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect the activity of superoxide dismutase （SOD）， reactive oxygen species （ROS）， glutathione peroxidase （GSH-Px）， and the level of malondialdehyde （MDA） in liver tissues. Immunohistochemistry was used to detect the expression of Nrf2 in the liver. Real time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the mRNA and protein expression levels of Nrf2 and HO-1 in liver tissues. ResultCompared with the normal group， the model group showed a significant increase in body mass， liver mass， and liver index （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed a significant decrease in body weight， liver mass， and liver index （P<0.01）. Compared with the normal group， the model group showed significantly increased TC， TG， and LDL levels （P<0.01）， and significantly decreased HDL levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced TC levels （P<0.01）， and significantly reduced TG levels （P<0.05）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced LDL levels （P<0.05）. The metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased HDL levels （P<0.05）. Compared with the normal group， the model group showed significantly increased ALT and AST activities （P<0.01）. Compared with the model group， all doses of modified Dahuang Huanglian Xiexintang and the metformin group showed significantly reduced ALT activities （P<0.05） and significantly reduced AST activities （P<0.01）. Compared with normal group， the model group showed significantly increased FBG at all time points （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly reduced FBG at 8， 10， 12 weeks. The OGTT results showed that compared with the normal group， the model group had significantly increased blood glucose at all time points （P<0.01）. Compared with the model group， the metformin group showed significantly reduced blood glucose at all time points （P<0.01）， and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced blood glucose at 90， 120 min （P<0.01）. HE pathology showed clear and regular liver cell structure in the normal group， while the model group showed disordered liver cell structure with visible fat vacuoles and a large number of deformed necrotic cells. The liver tissue structure improved in the metformin group and all doses of modified Dahuang Huanglian Xiexintang， with fewer necrotic cells. Compared with the normal group， the model group showed significantly reduced SOD and GSH-Px levels （P<0.01）， and significantly increased ROS and MDA levels （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased SOD and GSH-Px levels （P<0.01）， and significantly reduced MDA levels （P<0.01）. The medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced ROS levels （P<0.05）. Compared with the normal group， the model group showed significantly reduced Nrf2 and HO-1 mRNA expression levels （P<0.01）. Compared with the model group， the metformin group and the medium and high dose groups of modified Dahuang Huanglian Xiexintang showed significantly increased Nrf2 and HO-1 mRNA expression levels （P<0.05）. Immunohistochemistry showed that compared with the normal group， the model group had significantly reduced positive expression of Nrf2 and HO-1 （P<0.05）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed increased positive expression of Nrf2 and HO-1， with a significant increase in brown-yellow granules around the cell nucleus （P<0.05）. Western blot results showed that compared with the normal group， the model group had significantly reduced protein expression of Nrf2 and HO-1 （P<0.01）. Compared with the model group， the metformin group and all doses of modified Dahuang Huanglian Xiexintang showed significantly increased protein expression of Nrf2 and HO-1 （P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang can significantly improve the general condition and pathological changes of liver tissues in T2DM model rats. This improvement is likely achieved through ameliorating hepatic oxidative stress injury via regulating the Nrf2/HO-1 axis.

Type 2 diabetes mellitus （T2DM） is based on insulin resistance （IR） and insulin secretion deficiency， with the specific mechanisms still unclear. Current research involves mechanisms such as glycolipid toxicity， inflammatory response， oxidative stress damage， and mitochondrial dysfunction. Modern traditional Chinese medicine （TCM） scholars have named it "blood glucose collateral disease" based on the clinical characteristics and natural progression of T2DM. This condition is primarily manifested as abnormal blood sugar levels in the early stages， and as the disease progresses， it gradually causes widespread damage to the body's veins and collaterals， ultimately leading to lesions in vessels and collaterals. Among these， "spleen heat" （obesity type） is the most common clinical type of T2DM. The concept of "internal heat-induced elimination" runs through both the onset and complications of T2DM， with internal heat being a key factor in its pathogenesis. The clinical application of Dahuang Huanglian Xiexintang and its modifications has achieved significant therapeutic effects. This paper reviews the origins and treatment characteristics of Dahuang Huanglian Xiexintang， along with clinical application research and experimental studies related to T2DM treatment， involving mechanisms for regulating glucose and lipid metabolism disorders， improving IR， modulating inflammatory responses， combating oxidative stress damage， regulating autophagy-related signaling pathways， modulating intestinal flora， inhibiting pyroptosis， and alleviating endoplasmic reticulum stress， with the purpose to provide direction for further research on the prevention and treatment of T2DM and its related complications， to offer reference for developing Dahuang Huanglian Xiexintang as a rapid hypoglycemic Chinese patent medicine for obese T2DM， and to better guide the clinical promotion of this drug.

ObjectiveTo discuss the effect of modified Gegen Qinliantang （MGQT） on blood glucose and lipids and Takeda G protein-coupled receptor 5 （TGR5）-related pathways in pancreatic tissue of obese type 2 diabetes mellitus （T2DM） mice. MethodA total of 10 male specific pathogen free （SPF） m/m mice （7 weeks old） and 50 male SPF （7 weeks old） were adaptively fed for one week in SPF laboratory. The m/m mice were included in the blank group. T2DM was induce d in the 50 db/db mice. The model mice were randomized into the model group， metformin group （0.2 g·kg^-1）， high-dose， medium-dose， and low-dose （31.9， 19.1， 6.4 g·kg^-1） MGQT groups， with 10 in each group， and the drug dose was10 mL·kg^-1. The model group and the blank group received distilled water of the same volume. The administration lasted 12 weeks （once/day）. Fasting blood glucose （FBG） was detected regularly. After 12 weeks of administration， serum levels of glycated serum protein （GSP）， serum glucose （GLU）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected. Pathological changes in the pancreatic tissue were based on hematoxylin-eosin （HE） staining. Western blot was used to determine the protein expression of TGR5， protein kinase A （PKA）， phosphorylated （p）-PKA， cyclic-AMP response element binding protein （CREB）， p-CREB， proprotein convertase 1/3 （PC1/3）， and glucagon-like peptide-1 （GLP-1） in pancreatic tissues. The level of cyclic adenosine monophosphate （cAMP） in pancreatic tissue was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the blank group， the model group had pathological changes in pancreatic tissue， high levels of FBG， GSP， GLU， TC， TG， and LDL-C （P<0.01）， low level of HDL-C （P<0.05）， low protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in pancreatic tissue （P<0.01）， and low content of cAMP in the pancreas （P<0.01）. Pancreatic tissue lesion in the treatment groups were milder than that in the model group. Both the high-dose MGQT and metformin can reduce the levels of FBG， GSP， GLU， TC， TG， and LDL-C in db/db mice （P<0.05， P<0.01） and increase the level of HDL-C （P<0.01）. Except the GLP-1 protein in the medium-dose MGQT group， the protein expression of TGR5， p-PKA （Thr197）/PKA， p-CREB （Ser133）/CREB， PC1/3， and GLP-1 in the high-dose and medium-dose MGQT groups and the metformin group increased compared with that in the model group （P<0.05， P<0.01）. The content of cAMP in the pancreatic tissue of the high-dose and medium-dose MGQT groups and the metformin group was raised compared with that in model group （P<0.05， P<0.01）. ConclusionMGQT can improve the glucose homeostasis in db/db mice with T2DM by regulating TGR5/cAMP/GLP-1 signaling pathway-related protein expression.

ObjectiveTo observe the effect of modified Dahuang Huanglian Xiexintang on mitochondrial autophagy and browning of visceral adipose tissue in obese type 2 diabetes mellitus （T2DM） model ZDF rats. MethodForty ZDF rats were induced with a high-fat diet to establish an obese T2DM model. The rats were randomly divided into five groups： Model group， metformin group （0.18 g·kg^-1）， and high， medium， and low dose groups of modified Dahuang Huanglian Xiexintang （2.16， 1.08， 0.54 g·kg^-1）， with eight rats in each group. Additionally， eight ZDF （fa/+） rats were assigned to the normal group. All groups received an intragastric volume of 10 mL·kg^-1， with the model and normal groups receiving the same volume of purified water once daily for 12 weeks. Fasting blood glucose （FBG） was regularly measured. After 12 weeks of intervention， the body weight， epididymal fat weight， and serum levels of glucose （GLU）， glycated serum protein （GSP）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in epididymal fat tissue. Transmission electron microscopy （TEM） was employed to observe mitochondrial autophagy in adipocytes. Real-time PCR was used to detect the mRNA expression of hypoxia-inducible factor-1α （HIF-1α）， Bcl-2/adenovirus E1B 19 kDa interacting protein 3 （BNIP3）， microtubule-associated protein 1 light chain 3B （LC3B）， p62/SQSTM1， uncoupling protein 1 （UCP1）， iodothyronine deiodinase 2 （Dio2）， and PR domain containing 16 （Prdm16） in epididymal fat. Western blot was used to detect the protein expression of HIF-1α， BNIP3， LC3B， p62， and UCP1 in epididymal fat. ResultCompared with the normal group， the model group showed pathological changes in epididymal fat， with adipocyte mitochondrial condensation and numerous autophagosomes indicating mitochondrial autophagy. The model group also exhibited significantly increased body weight， epididymal fat weight， FBG， GLU， GSP， TC， TG， and LDL-C levels （P<0.01）， significantly decreased HDL-C levels （P<0.01）， significantly elevated mRNA and protein expression of HIF-1α， BNIP3， and LC3B （P<0.01）， significantly reduced mRNA and protein expression of p62 and UCP1 （P<0.01）， and significantly reduced mRNA expression of Dio2 and Prdm16 （P<0.01）. Compared with the model group， all intervention groups showed varying degrees of improvement in epididymal fat pathology. The metformin group and high-dose modified Dahuang Huanglian Xiexintang group displayed intact mitochondrial morphology， clear cristae， uniform matrix， and few autophagosomes and autophagosomes in the adipocyte cytoplasm. The metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang showed significantly reduced body weight and epididymal fat weight （P<0.01）. The epididymal fat index was reduced in all intervention groups （P<0.05）， and FBG was lowered in all intervention groups （P<0.01）.Serum GSP， GLU， TG， and LDL-C levels were reduced in the metformin group and the high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The serum TC level was significantly reduced in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.01）， and HDL-C levels were significantly increased in all intervention groups （P<0.05， P<0.01）. The mRNA and protein expression of HIF-1α， BNIP3， and LC3B were significantly reduced， and UCP1 protein expression was significantly increased in the metformin group and high- and medium-dose groups of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. The mRNA and protein expression of p62， Dio2， and Prdm16 were significantly increased in the metformin group and high-dose group of modified Dahuang Huanglian Xiexintang （P<0.05， P<0.01）. ConclusionModified Dahuang Huanglian Xiexintang may inhibit mitochondrial autophagy and promote the browning of visceral adipose tissue through the HIF-1α/BNIP3/LC3B pathway， thereby improving glucose and lipid metabolism in obese T2DM rats.

ObjectiveTo observe the effect of modified Gegen Qinliantang on the expression levels of proteins related to the farnesoid X receptor/small heterodimer partner/peroxisome proliferator-activated receptor α （FXR/SHP/PPARα） signaling pathway in the liver tissue of db/db model mice with type 2 diabetes mellitus （T2DM） and explore the underlying mechanism of action of modified Gegen Qinliantang. MethodThirty db/db mice were randomly divided into model group， metformin group （0.2 g·kg^-1）， and high-， medium-， and low-dose modified Gegen Qinliantang groups （31.9， 19.1， 6.4 g·kg^-1）， with 6 mice in each group. An additional six m/m mice were assigned to the blank group. Respective drugs were administered via oral gavage for 12 weeks. Mouse body weight， fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels were measured. Oil red O staining was used to observe hepatic lipid accumulation and periodic acid-schiff （PAS） staining was used to assess hepatic glycogen deposition. Ammonium ferric sulfate staining was used to observe cholesterol deposition in intestinal tissues. Western blot was employed to detect the expression of FXR， cholesterol 7α-hydroxylase （CYP7A1）， SHP， and PPARα proteins in liver tissues， and enzyme-linked immunosorbent assay （ELISA） was used to measure serum free fatty acid （FFA） levels. ResultAt the end of the treatment， compared with the blank group， the model group exhibited significant increases in mouse body weight， FBG， FFA， TC， TG， and LDL-C levels （P<0.01）， along with significant hepatic lipid droplets， reduced hepatic glycogen， noticeable cholesterol accumulation in intestinal tissues， significantly decreased expression of FXR， SHP， PPARα proteins， and significantly increased expression of CYP7A1 protein in liver tissues （P<0.01）. Compared with the model group， the metformin group and the high- and medium-dose modified Gegen Qinliantang groups demonstrated significant reductions in mouse body weight， FBG， FFA， TC， TG， LDL-C levels （P<0.05， P<0.01）， significant increases in HDL-C levels （P<0.05， P<0.01）， decreased hepatic lipid accumulation， increased hepatic glycogen， reduced intestinal cholesterol accumulation， significantly increased expression of FXR， SHP， PPARα proteins， and significantly decreased expression of CYP7A1 protein in liver tissues （P<0.01）. ConclusionModified Gegen Qinliantang may regulate the FXR/SHP/PPARα signaling pathway to suppress FFA levels and improve lipid metabolism in T2DM mice.