Gegen Qinliantang and Its Modified Prescriptions Ameliorate Insulin Resistance in Type 2 Diabetes Mellitus： A Review / 中国实验方剂学杂志

Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）. This prescription consists of Puerariae Lobatae Radix， Scutellariae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior， thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method， Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus （T2DM）， which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex， mainly related to heredity， lifestyle， environment， diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically， Gegen Qinliantang is often applied with modification， or in combination with Western drugs， demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms， reduce the occurrence of complications， and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways， alleviating oxidative stress， and modulating gut microbiota to treat T2DM. Nevertheless， more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease， this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.

Efficacy of Kushen decoction on high-fat-diet-induced hyperlipidemia in rats.

OBJECTIVE: To investigate the efficacy and underlying mechanisms of action of Kushen decoction on high-fat-diet-induced hyperlipidemia in rats using RNA-seq technology. METHODS: The efficacy of a Kushen decoction, at a concentration of 1 mL/g of crude medicine prepared according to the method commonly used in clinical practice, was investigated on 24 specific pathogen-free male Sprague-Dawley rats. Liver tissues were compared using RNA-Seq technology. The differentially expressed genes were further investigated by real-time fluorescent quantitative polymerase chain reaction (qPCR and Western blot (WB). RESULTS: Serum triglycerides (TG), liver low-density lipoprotein cholesterol (LDL-C), body weight, body length, and Lee's index were significantly increased in the untreated hyperlipidemia-induced group (model) compared with the control group, whereas liver high-density lipoprotein cholesterol (HDL-C) was significantly decreased. Serum TG, liver LDL-C, bodyweight, and Lee's index were decreased in the high-dose Kushen decoction group (HDKS) compared with the model group, whereas liver HDL-C was significantly increased. Similarly, liver TG tended to decline in the HDKS group. Comparison of the gene expression profiles in the livers from different groups indicated that the Kushen decoction significantly affected metabolic pathways, PPAR signalling pathway, and circadian rhythm ( ≤ 0.05), with the genes ARNTL, PER3, and CLOCK being differentially expressed. qPCR and WB analysis confirmed the differential expression of the genes discovered by transcriptomics analysis. CONCLUSION: The Kushen decoction may achieve a lipid-lowering effect on hyperlipidemic rats by regulating metabolic pathways and the circadian rhythm pathway and in particular, their related genes ARNTL, PER3, and CLOCK.

Study on the Mechanism of Gegen Qinlian Decoction for Lowering Blood Lipids and Preventing Blood Glucose Increase Based on Intestinal Flora / 中国药房

OBJECTIVE：To study the ef fects of Gegen qinlian decoction （GGQLD）on blood lipid and blood glucose of hyperlipidemia（HLP）model rats ，and to explore its mechanism from the perspective of intestinal flora. METHODS ：Totally 48 rats were randomly divided into blank control group （n＝8）and modeling group （n＝40）. For consecutive 5 weeks，model group was given high-lipid diet to induce HLP model ；blank control group was given routine diet. After modeling ，30 modeling rats were randomly divided into model group ，simvastatin group （positive control ，10 mg/kg），GGQLD high-dose ，medium-dose and low-dose groups （14.85，4.95，1.65 g/kg，by crude drug ），with 6 rats in each group. Blank control group and model group were given constant volume of normal saline intragastrically ；administration groups were given relevant medicine intragastrically ，once a day，for consecutive 11 weeks. At the same time ，each group was continuously given corresponding diet. After the last medication ， body mass and body length of rats were determined ，and Lee ’s index was calculated. Serum levels of TG ，TC，HDL-C，LDL-C and fasting blood glucose （FBG）were determined in rats. DNA of rat caecum content was extracted for 16S rRNA V 3-V4 region sequencing. The Two-part model was used to analyze the correlation between intestinal flora with lipids and blood glucose. RESULTS：After 11 weeks of administration ，compared with blank control group ，the body mass ，body length ，Lee’s index ， serum levels of TC ，TG，HDL-C and FBG of model group were increased significantly （P＜0.05 or P＜0.01），while the level of HDL-C was decreased significantly （P＜0.05）. Compared with model group ，body mass and Lee ’s index and serum levels of TG ， FBG of rats in GGQLD high-dose group ，and serum levels of TC ，TG in GGQLD medium-dose group ，as well as serum level of TG of rats in GGQLD low-dose group was decreased significantly （P＜0.05 or P＜0.01）. Correlation analysis with intestinal flora showed that TC and TG shared 3 operational taxonomic units （OTU），including OTU 559，OTU701 and OTU 135（OTU135 was also shared with FBG ），which were all positively correlated with the level of TC ，TG and FBG （P＜0.01）. The three OTU were annotated as Tyzzerella of Spirillaceae ，Anaerotruncus of Verrucaceae and Peptoclostridium of Streptococcidae ，respectively. High-dose and low-dose GGQLD had a down-regulating effect on Tyzzerella and Anaerotruncus（P＜0.05 or P＜0.01），while had up-regulating effect on Peptoclostridium（P＜0.01）. CONCLUSIONS ：High-dose GGQLD （14.85 g/kg）can effectively reduce the body mass and blood lipid of HLP model rats ，and can prevent the abnormal increase of blood glucose of model rats. The mechanism may be associated with that the reduction of intestinal flora （Tyzzerella，Anaerotruncus）content.

Clinicopathological characteristics and prognostic factors analysis of combined hepatocellular-cholangiocarcinoma / 中华消化外科杂志

Objective To analyze the clinicopathological characteristics and prognostic factors of combined hepatocellular-cholangiocarcinoma (cHCC-CC).Methods The retrospective cohort study was conducted.The clinicopathological data of 72 patients with primary hepatocellular carcinoma (HCC) who were admitted to the Xiangya Hospital of Central South University between January 2005 and December 2014 were collected.Thirty-two patients who were diagnosed with cHCC-CC by postoperative pathological examination were allocated into the cHCC-CC group and 40 patients who were diagnosed with HCC by postoperative pathological examination were allocated into the HCC group.Observation indicators:(1) clinicopathological characteristics:male,age ＞ 60 years,positive hepatitis B surface antigen (HBsAg),positive alpha-fetoprotein (AFP),positive CA19-9,positive carcinoembryonic antigen (CEA),liver cirrhosis,Child-Pugh grade A,tumor diameter ＞ 5 cm,tumor with capsule,solitary tumor,portal vein tumor thrombus (PVTT),cancer thrombus of the bile duct,positive lymph node metastasis,stage Ⅰ-Ⅱ of TNM stage,Edmondson-Steiner stage Ⅰ-Ⅱ;(2) pathological features of surgical incision specimens;(3) follow-up situations:median survival time,1-,3-,5-year survival rates and tumor-free survival rate;(4) prognostic factors analysis of patients with cHCC-CC:AFP,CA19-9,liver cirrhosis,tumor diameter,tumor capsule,number of tumor,PVTT,cancer thrombus of the bile duct,lymph node metastasis,Edmondson-Steiner stage,volume of intraoperative blood loss,intraoperative blood transfusion,distant from surgical margin.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients and tumor recurrence or metastasis up to October 2015.Comparison of count data was analyzed using the chi-square test.The survival curve was drawn by the Kaplan-Meier method,and the survival analysis was done using the Log-rank test.The prognostic analysis was done using the COX regression model.Results (1) Clinicopathological characteristics:positive CA19-9,tumor with capsule,cancer thrombus of the bile duct and positive lymph node metastasis were detected in 16,4,12,6 patients in the cHCC-CC group and 5,17,1,1 patients in the HCC group,respectively,with statistically significant differences between the 2 groups (x2=10.471,9.723,13.005,4.009,P ＜ 0.05).(2) Pathological features of surgical incision specimens:pathological results showed that surgical incision specimens in the cHCC-CC group had characteristics of HCC tissues and cholangiocarcinoma tissues.The antigenic activity of hepatic cells in paraffin sections,Cytokeratin 7,Cytokeratin 19 and progenitor cell markers were positive by immunohistochemical staining detection.Patients in the HCC group had characteristics of HCC tissues,with positive AFP using immunohistochemical staining detection.(3) Follow-up situations:all the 72 patients were followed up for 5.0-74.0 months with a median time of 41.0 months.The median survival time,1-,3-,5-year survival rates,1-,3-,5-year tumor-free survival rates were 14.5 months,62.3％,38.9％,19.1％,50.0％,23.9％,4.0％ in the cHCC-CC group and 46.8 months,82.3％,57.4％,38.6％,72.9％,35.6％,17.6％ in the HCC group,respectively,with statistically significant differences in overall survival and tumor-free survival between the 2 groups (x2=4.231,3.881,P ＜ 0.05).(4) Prognostic factors analysis of patients with cHCC-CC:results of univariate analysis showed that CA19-9,tumor capsule,number of tumor,cancer thrombus of the bile duct,lymph node metastasis and Edmondson-Steiner stage were related factors affecting prognosis of patients with cHCC-CC [HR =1.824,0.227,0.441,1.421,1.887,2.745,95％ confidence interval (CI):1.126-2.172,0.118-0.654,0.318-0.764,1.071-4.231,1.017-5.643,1.223-6.421,P ＜ 0.05].Results of multivariate analysis showed that lymph node metastasis and stage Ⅲ-Ⅳ of Edmondson-Steiner stage were independent risk factors affecting prognosis of patients with cHCC-CC (RR =1.658,2.912,95％ CI:1.027-7.542,1.143-6.582,P ＜0.05).Conclusions The positive CA19-9,tumor without capsule,cancer thrombus of the bile duct and positive lymph node metastasis can partly predict cHCC-CC.The prognosis of patients with cHCC-CC is worse than that with HCC.The positive lymph node metastasis and stage Ⅲ-Ⅳof Edmondson-Steiner stage are independent risk factors affecting prognosis of patients with cHCC-CC.

Mesohepatectomy for large and centrally located hepatocellular carcinoma / 中华肝胆外科杂志

Objective To evaluate the safety and efficacy of mesohepatectomy for large and centrally located hepatocellular carcinoma.Methods A retrospective study was carried out on 136 pa tients who underwent mesohepatectomy for large and centrally located hepatocellular carcinoma at Xiangya Hospital,Central South University,from 2001 to 2007.Intraoperative/post operative data and long-term survivals were analyzed.Results Vascular occlusion time,operative time,intraoperative blood loss,intraoperative blood transfusion and hospital stay were (13.3 ± 9.1) min,(173.1 ±41.1)min,(548.7±320.5)ml,(511.4±231.7)ml and (18.6±8.8)d,respectively.Four patients developed major complications.There was no in-hospital death.The 1-,3-,and 5-year overall survival rates and disease-free survival rates were 71％,46％,29％ and 65％,40％,24％,respectively.Conclusions Mesohepatectomy for large and centrally located hepatocellular carcinoma preserved the maximum amount of functional liver parenchyma.It is safe and reliable and may be used as the treatment of choice.

Preliminary study of metabonomcs on aqueous extract of Evodia rutaecarpa in sprague-dawley rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the change of endogenous metabolites of SD rats administrated of aqueous extract of Evodiae rutaecarpa.</p><p><b>METHOD</b>Six SD rats had been successively administrated aqueous extract of E. rutaecarpa (0.3857 g x kg(-1)) for 33 days. An agilent 1200 6410 triplequadrupole mass spectrometer was used for the analysis of endogenous metabolites in rat urine samples. These data was analyzed by the principal component analysis (PCA) and PLS-DA using the SIMCA-P 10.0 software.</p><p><b>RESULT</b>The significant difference in metabolic profiles between the control group and the dosed group was well observed by PCA of the MS data.</p><p><b>CONCLUSION</b>The E. rulaecarpa has changed the endogenous metabolites of SD rats. This work can provide the base for the further research on the interpretation of drug property of E. rulaecarpa.</p>

Laparoscopic cholecystectomy for acute gallstone pancreatitis without jaundice:Report of 95 cases / 中国微创外科杂志

Objective To explore the feasibility and the selection of laparoscopic cholecystectomy(LC) for the treatment of acute gallstone pancreatitis(AGP) without jaundice.Methods Laparoscopic cholecystectomy had been performed in 95 patients with AGP accompanying no jaundice from July 1996 to July 2004 in this hospital.All of the patients had a history of conservative treatment.Selective LC was performed in 79 patients after their symptoms were relieved,while emergent LC was required in 16 patients because of failure of response to conservative treatment.Results All the operations were successfully completed.The operation time was 40~328 min(mean,103 min),and the intraoperative blood loss was 0~210 ml(mean,35 ml). Intraoperative cholangiography was carried out in all the 95 patients and succeeded in 92.Thirteen patients were found having lower common bile duct stones and then were cured with endoscopic retrograde cholangiopancreatography(ERCP) and endoscopic spincterotomy(EST).No conversion to open operation was required.No postoperative biliary hemorrhage or leakage occurred.No fatal case was seen.Pathological examinations following operation revealed multiple small or sand-like stones in the gallbladder.Follow-up in 39 patients for 1 months ~ 5 years found no recurrence of pancreatitis or cholelithiasis.Conclusions Laparoscopic cholecystectomy should be performed as early as possible in the treatment of AGP without jaundice.Use of intraoperative cholangiography and postoperative EST should be emphasized in proper cases.