The role of FGF21 in inhibition of heart failure with empagliflozin and related mechanisms / 药学学报

The aim of this study is to investigate the role of fibroblast growth factor 21 (FGF21) in empagliflozin (EMP) in treatment of heart failure and the related mechanisms. FGF21 knockout (FGF21 KO) and littermate wild-type (WT) mice induced by doxorubicin (Dox) were used to establish heart failure mouse model in vivo. The experiment process and animal welfare follow the regulations of Animal Ethics Committee of Hefei University of Technology strictly. The results suggest that Dox (5 mg·kg-1) induced typical heart failure symptoms in both WT and FGF21 KO mice. In WT mice, EMP (10 mg·kg-1) significantly improved Dox-induced cardiac atrophy, decreased myocardial systolic function, decreased left ventricular ejection fraction and shortened fraction; EMP treatment also significantly inhibited the increase of Dox-induced cardiotoxicity indexes (aspartate amino transferase, creatine kinase, hydroxybutyrate dehydrogenase, lactate dehydrogenase) in mice. Dox induced cardiac fibrosis, inflammation and oxidative stress were also significantly improved by EMP. However, in FGF21 KO mice, the therapeutic effects of EMP on heart failure was significantly inhibited. The results suggest that the function of EMP in treating heart failure partly depends on the presence of FGF21, and the mechanism may be related to the effect of FGF21 on improving fibrosis, inflammation and oxidative stress.

Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head / 中华外科杂志

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

Proliferative and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Andrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.</p><p><b>METHODS</b>Cell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.</p><p><b>RESULTS</b>Andrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.</p><p><b>CONCLUSIONS</b>Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.</p>

Effect of andrographolide on proliferation and apoptosis of gastric cancer BGC-823 cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of andrographolide (AD) on proliferation, cell cycle and apoptosis of human gastric cells line BGC-823.</p><p><b>METHODS</b>MTT assay, flow cytometry and Annexin-V/PI double-staining flow cytometry assay were used to evaluate the effect of AD on proliferation, cell cycle and apoptosis of BGC-823 cells respectively. Optical microscope and transmission electron microscopy were used to observe the cell morphological changes.</p><p><b>RESULTS</b>A time- and concentration-dependent proliferative inhibition effect of AD was demonstrated in BGC-823 cells. AD concentration lower than 7.5 mg/L possessed weak inhibitory effect,while concentration between 15.0-60.0 mg/L possessed higher inhibitory effect. The concentration higher than 60.0 mg/L had no significant increase of inhibitory effect. IC50 of AD at 24, 48 and 72 h was (35.3±4.3), (25.5±3.5) and (18.2±2.7) mg/L respectively. Compared with the negative control group, the number of G0/G1 phase cells increased significantly (P<0.05), while the number of S and G2/M phase cells decreased after incubation with AD for 48 h, and the alteration was in a concentration-dependent manner. AD arrested BGC-823 cells at the G0/G1 phase of the cell cycle. After incubation with 7.5, 10.0 and 15.0 mg/L AD for 24 h, the early apoptotic rates of BGC-823 cells were (19.3±4.7)%, (29.4±4.1)% and (52.7±6.7)% respectively, and the late apoptotic rates were (10.8±1.8)%, (10.9±4.7)% and (14.7±4.8)% respectively. Both the early apoptotic rates and the late apoptotic rates increased significantly compared to the control group (all P<0.05),and the alteration was in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Andrographolide can inhibit BGC-823 cells proliferation, arrest BGC-823 cells in G0/G1 phase and induce apoptosis, and may be a potential traditional Chinese medicine with anti-cancer effect.</p>

Beneficial effects of continual jejunal interposition after subtotal gastrectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The ideal post-gastrectomy reconstruction procedure should maintain the normal digestive function and restore intestinal transit to improve the patient quality of life. The aim of this study was to evaluate the effects of integral continual jejunal interposition after subtotal gastrectomy on the nutritional status, glucose levels, and gastric-intestinal motility.</p><p><b>METHODS</b>The study investigated the effects of the integral continual jejunal interposition, the Billroth I and Billroth II operations, and the isolated jejunal interposition following subtotal distal gastrectomy on the blood glucose, insulin, routine blood parameters, liver function, and myoelectrical activity in Beagle dogs.</p><p><b>RESULTS</b>The weights of the dogs decreased during the first post-operative weeks. Dogs in the integral continual jejunal interposition, Billroth I, and Billroth II groups gained significantly more weight by 8 weeks. The prognosis nutrition index of the dogs decreased in the first 2 post-operative weeks and increased significantly by 4 weeks in the integral continual jejunal interposition and Billroth I groups. The group with duodenal exclusion (Billroth II) had significantly higher glucose levels compared to the normal control group. The insulin curve was much higher in dogs that underwent the Billroth I, continual jejunal interposition, and isolated jejunal interposition than the Billroth II and normal groups. The frequencies of fasting and postprandial jejunal pacesetter potentials (PPs) were greater in the continual jejunal interposition and Billroth I groups than that in the isolated jejunal interposition and Billroth II groups. The percentage of aboral propagation of PPs was greater in the continual jejunal interposition group than the Billroth I, isolated jejunal interposition, and Billroth II groups.</p><p><b>CONCLUSION</b>Continual jejunal interposition after subtotal gastrectomy avoids jejunal transection, maintains the duodenal passage and food storage bags, and reduces the influence of blood glucose and insulin.</p>

Clinicopathological characteristics and prognosis of early gastric cancer after gastrectomy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Assessment of lymph node metastasis (LNM) is important in early gastric cancer (EGC) and affects treatment decisions. However, the relationship between clinicopathological characteristics and LNM in EGC remains unclear. This study therefore explored favorable predictors of LNM in EGC.</p><p><b>METHODS</b>A total of 716 specimens from gastric cancer patients who underwent curative gastrectomy between 1996 and 2003 at Zhejiang Provincial People's Hospital were reviewed. Forty-five cases were EGC, and clinicopathological characteristics such as gender, age, tumor size, location, gross type, differentiation, invasion depth, and vessel involvement were assessed to identify predictive factors for LNM and survival time.</p><p><b>RESULTS</b>The overall cumulative 5-year survival rate of EGC patients was 88.92%. Among these, 22.4% developed LNM, which was associated with a poor 5-year survival rate of only 72.7%. Patients with tumors larger than 2 cm in diameters, with depth of tumor invasion to the submucosa, and with positive lymphatic or nerve involvement were also inclined to have poorer survival performances. EGC limited to the mucosa but poorly differentiated also had a high risk for LNM. Multivariate analysis identified lymphatic invasion and tumor size as independent prognosis factors related to survival in EGC patients.</p><p><b>CONCLUSIONS</b>Careful planning is required in EGC patients at high risk of lymph node metastases. Endoscopic mucosal resection or endoscopic submucosal dissection and laparoscopic partial gastrectomy should be cautiously used in EGC, and curative gastrectomy including lymphatic dissection and postoperative adjuvant therapy might be considered to improve the prognosis.</p>

Oral glucose tolerance test and insulin response in Beagle dogs after subtotal distal gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of reconstruction techniques after subtotal gastrectomy on postoperative glucose and insulin levels after oral glucose tolerance test (OGTT).</p><p><b>METHODS</b>Distal gastrectomy was performed in 38 Beagle dogs. Reconstruction techniques used included integral continual jejunal interposition (n=9), Billroth I( (n=6), Billroth II( (n=7), and isolated jejunal interposition (n=8). Eight controls were used. OGTT was conducted to examine the changes in glucose and insulin levels.</p><p><b>RESULTS</b>Compared to controls, glucose significantly increased in all the 4 operative groups and peaked at 60 min. Billroth II( was associated with the most significant increase. Insulin level significantly increased in all the experimental groups in response to food stimulus and peaked at 60 min. However, the increase of insulin in Billroth II( group was not as prominent as in other groups.</p><p><b>CONCLUSIONS</b>Fluctuation of blood glucose after gastrectomy may be mitigated and insulin elevated if duodenal passage is preserved. Continual jejunal interposition should be given priority when Billroth I( reconstruction is not feasible.</p>

Experimental research of integral continuous jejunal interposition after subtotal distal gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate nutritional status, myoelectrical activity, and gastrointestinal tract emptying capacity after integral continuous jejunal interposition following subtotal gastrectomy.</p><p><b>METHODS</b>According to different re-construction techniques, 30 Beagle dogs were divided into four groups after subtotal distal gastrectomy: group 1(n=9, integral continuous jejunal interposition), group 2(n=6, Billroth I(), group 3(n=7, Billroth II(), group 4(n=8, isolated jejunal interposition). Blood cell counts, liver function, myoelectrical activity and the rate of gastrointestinal tract emptying were compared among the four groups.</p><p><b>RESULTS</b>At week 12 after operation, the body weight in group 1 [(9.65±1.54) kg] was significantly higher than that in group 2[(9.25±1.76)kg], group 3[(9.31±1.54)kg] and group 4[(7.77±1.46)kg]. At week 4, the prognostic nutritional index in group 1(2671.9±49.9) was significantly higher than that in group 3(2555.9±54.7) and group 4(2440.9±54.3), but similar to that in group 2(2791.8±54.3). At week 6, the fasting and postprandial frequency of jejunal pacesetter potentials in group 1 were higher than those in group 3 and group 4(P<0.05) but comparable with those in group 2. The emptying rate of food in the four groups were 95.4%, 91.3%, 93.1% and 94.2%, respectively and there were no significant differences(P>0.05). However, as compared with group 2 and group 3, group 1 had longer operative time and later regular diet resumption, more severe abdominal adhesion(P<0.05).</p><p><b>CONCLUSION</b>Continuous jejunal interposition should be considered when Billroth I( is not feasible after subtotal gastrectomy.</p>

Relationship between the expression of vascular endothelial growth factor, fms-like tyrosine kinase-1 and biological behavior in gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase (Flt-1) mRNA and tumor progression, microvessel density and survival time in gastric carcinoma.</p><p><b>METHODS</b>In situ hybridization and immunohistochemical techniques were used to detect the gene expression of VEGF, Flt-1 and CD34 in 118 gastric carcinoma specimens.</p><p><b>RESULTS</b>In situ hybridization revealed that positive expression rates of VEGF and Flt-1 mRNA in gastric carcinoma were 54.24% and 55.9% respectively. There was a significant correlation between the expression of VEGF and Flt-1 mRNA and growth pattern, the depth of tumor invasion, vessel invasion, lymph node and distant metastasis (P < 0.01). The mean tumor microvessel densities (MVD) in patients of stage T3-T4 or those with vessel invasion, lymph node and distant metastases were significantly higher than those of stage T1-T2 and without metastases (P < 0.01). MVD value was correlated with the expression levels of VEGF and Flt-1 mRNA (P < 0.01). The mean survival time and survival rate of patients with positive mRNA expression and mean MVD value >or=54.9/mm2 were significantly lower than those of patients with negative mRNA expression and mean MVD value < 54.9/mm2.</p><p><b>CONCLUSIONS</b>The expression of VEGF and Flt-1 can promote tumor angiogenesis and contribute to tumor invasion and metastasis in gastric carcinoma. VEGF and Flt-1 may serve as valuable indicators of biological behaviour, prognosis and target of gene therapy in gastric carcinoma.</p>

Comparative studies on isolation and purification of Chinese medicine decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate different methods by treating water-decocted liquid of 6 Chinese medical herbs and 4 co-prescription respectively with alcohol, ultrafilter, macroporousresin and clarifier.</p><p><b>METHOD</b>The contents of target component in those extracts were determined with HPLC or titration, and quantitative and qualitative determination of the impurity components, such as polysaccharide and protein, was made.</p><p><b>RESULT</b>Each method showed its advantages and disavantages.</p><p><b>CONCLUSION</b>Different method can be chosen according to the clinical and preparation demands or the characteristic of components.</p>