Gindenosides are the active ingredients of Panax ginseng. 20 (S) -protopanaxadiolocotillol type epimers are the main metabolites of 20 (S) -protopanaxadiol. The previous studies showed that there are stereoselectivity difference in pharmacodynamics and pharmacokinetics between 24R-epimer and 24S-epimer. The purpose of this study was to explore the excretion of the epimers in bile, feces and urine of rat. Liquid chromatography tandem mass spectrometry method has been performed for determination of 24R-epimer and 24S-epimer in bile, feces and urine. 24R-epimer or 24S-epimer was intragastric administered to rats at a single dose of 10 mg x kg(-1). Results showed that after administration the recovery of 24R-epimer and 24S-epimer in feces was 17.69% and 17.09%, respectively, while both of the two epimers were hardly detected in urine. The 48 h cumulative biliary excretion rate of 24R-epimer was 8.01% after administration, while only 1.47% for 24S-epimer. It indicated that there are stereoselectivity in biliary excretion of the epimers with intragastric administration.
Animals ; Bile ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacokinetics ; Feces ; chemistry ; Ginsenosides ; chemistry ; pharmacokinetics ; Male ; Mass Spectrometry ; Panax ; chemistry ; Rats ; Rats, Sprague-Dawley ; Stereoisomerism ; Urine ; chemistry

Objective:To compare the safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk gastric stromal tumor, and to evaluate whether there was evident benefits of postoperative adjuvant treatment with imatinib.Methods:A retrospective study was conducted on 72 patients with moderate risk gastric stromal tumors (5-10 cm in diameter) who received operation in Nanjing Drum Tower Hospital from January 2010 to July 2020. There were 28 cases in the laparoscopy group and 44 cases in the laparotomy group. The clinical features, pathological data, perioperative results and hospitalization costs were compared between the two groups. The survival rates of postoperative adjuvant therapy with or without imatinib were analyzed and compared.Results:There was no significant difference in clinicopathological features between the two groups ( P>0.05). The incidences of postoperative complications in the laparoscopy group and the laparotomy group were 32.1% (9/28) and 52.3% (23/44) respectively, showing no significant difference ( P=0.094). Compared with the laparotomy group, both the hospital stay (12.5±3.2 days VS 15.0±3.5 days, P=0.004) and the median postoperative hospital stay (7.5 days VS 9.0 days, P=0.006) in the laparoscopy group were significantly shorter, and the first exhaust time was significantly shorter ( P=0.003). During the median follow-up period of 58 months (13-129 months), there was no tumor-related death. Two cases died of breast cancer and heart disease in the laparotomy group, and 1 case died irrelevant to gastric stromal tumor in the laparoscopy group. Of the 72 patients, 40 received postoperative imatinib adjuvant therapy, 22 cases (50.0%) in the laparotomy group and 18 cases (64.3%) in the laparoscopy group, with no significant difference in the proportion ( χ2=1.414, P=0.234). There was significant difference in the overall survival rate between the group treated with imatinib and the group without imatinib ( P=0.015). Conclusion:Laparoscopic resection is safe and effective for intermediate-risk gastric stromal tumor of 5-10 cm. Taking imatinib adjuvant treatment does not increase overall survival rate of patients with intermediate-risk gastric stromal tumors (5-10 cm), and there is no tumor-related death, recurrence or metastasis for those who did not accept imatinib adjuvant treatment after R0 resection.

BACKGROUND: Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy. METHODS: In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1. RESULTS: The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t = 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t = 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t = 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein. CONCLUSION Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.
Adaptor Proteins, Signal Transducing ; Adult ; Arteriosclerosis Obliterans/genetics* ; Autophagy ; GRB2 Adaptor Protein ; Humans ; Phosphoproteins/metabolism* ; Phosphorylation ; Protein Binding ; Signal Transduction

Objective:To evaluate the long-term efficacy of endoscopic transluminal drainage(ETD) for acute pancreatitis complicated with walled-off necrosis (WON) or pancreatic pseudocyst (PPC).Methods:A total of 79 patients who were diagnosed as having WON or PPC by abdominal CT or ultrasound and treated with ETD in Nanjing Drum Tower Hospital were enrolled. Past medical records and follow-up by phone call after discharge were analyzed for long-term outcomes including endocrine and exocrine functions and long-term quality of life.Results:A total of 50 patients were enrolled, including 31 patients with infected WON/PPC and 19 patients with uninfected WON/PPC. Seventeen patients (54.84%) in the infected WON/PPC group and 11 patients (57.89%) in the uninfected WON/PPC group lost 5% or more of their weight. There were no significant differences in the proportion of cases of weight loss of 5% or more ( P=0.833), or the weight loss between the two groups (12.59±8.89 kg VS 10.91±2.47 kg, P=0.522). Only one patient in the infected WON/PPC group had chronic abdominal pain. There was no significant difference in the Izbicki score between the two groups (23.79±6.74 VS 22.03±3.21, P=0.295). None of the patients developed steatorrhea after discharge. Five patients (16.67%, 5/30) in the infected WON/PPC group and 6 patients (40.00%, 6/15) in the uninfected WON/PPC group developed endocrine insufficiency with no significant difference ( P=0.140). Greater risk of secondary diabetes resulted from higher low-density lipoprotein cholesterol ( HR=1.9, 95% CI: 1.0-3.4, P=0.044)and triglycerides ( HR=1.2, 95% CI: 1.0-1.3, P =0.029). Conclusion:ETD is safe and effective for WON and PPC. But there is possibility that patients develop secondary diabetes. Additionally, greater risk of secondary diabetes results from higher low-density lipoprotein cholesterol and triglycerides.

OBJECTIVETo study the potential risk factors of human infecting with Streptococcus suis.

METHODS1: M matched case-control study was conducted. 29 human cases of Streptococcus suis infection in the early phase were included in the case group, Patients' family members, neighbors and peoples who had worked together with patients to handle deceased or sick pigs in the last week were recruited as matched controls. There were 147 controls in total. Both cases and controls received questionnaire investigation including the ways to contact sick/dead pigs. Conditional logistic regression was employed to analyze matching data.

RESULTSAccording to the results of multivariate analysis, slaughtering (OR = 11.978, 95% CI: 3.355-42.756), carcasses cutting and processing (OR = 3.008, 95% CI: 1.022-8.849) sick/dead pigs were associated with cases related to human Streptococcus suis infection. The attributable risk proportion were 91.65% and 66.76% respectively. The other types of exposures to sick/ dead pigs, including feeding, selling, burying and eating, were not associated with the human Streptococcus suis infection in our study population.

CONCLUSIONSlaughtering, carcasses cutting and processing sick/dead pigs were important risky behavior for humans to be infected by Streptococcus suis.

Adult ; Aged ; Case-Control Studies ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Occupational Exposure ; adverse effects ; statistics & numerical data ; Risk Factors ; Streptococcal Infections ; epidemiology ; etiology ; microbiology ; Streptococcus suis ; physiology

OBJECTIVETo describe the clinical and epidemiological features of dead cases with human Streptococcus suis infections, and to find the target population for preventing death and the related indicators.

METHODSEpidemiological investigation on human Streptococcus suis infections was implemented used unified questionnaires. Analysis on dead cases and survival cases (as contrast) was done.

RESULTSThe population with highest fatality rate was in 40-49 age group. 97.37% of dead cases had toxic shock syndrome. The mean interval from onset to admission was 0.76 days, and the mean course was 2.11 days. The progression among dead cases was faster than that among survival cases. Chief clinical manifestations of dead cases that are more frequent than survival cases are purpura (73.68%), diarrhea (50.0%), dyspnea (21.05%), conjunctival congestion (34.21%), etc. Renal impairment and liver involvement in dead cases were more significant than that in survival cases. No significant difference between mean incubation period, exposure rates of main risk factors in dead cases and in survival cases was found.

CONCLUSIONPreventing toxic shock syndrome might reduce the fatality rate. The target population for preventing death is aged > or = 40. Liver function and renal function testing might be indicators for monitoring the progression of human Streptococcus suis infections.

Adult ; Aged ; China ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Streptococcal Infections ; blood ; microbiology ; mortality ; pathology ; Streptococcus suis ; physiology ; Young Adult

Objective To investigate the effect of microRNA-9-5p (miR-9-5p) regulating transient receptor potential melastatin 7 (TRPM7) on myocardial ischemia-reperfusion (MIR) in rats. Methods Thirty-two SD rats were divided into sham operation group, model group, miR-9-5p overexpression group and empty vector control group. The MIR model was established by ligation of left coronary artery. The sham operation group was not ligated. miR-9-5p agomir and agomir NC were injected into tail vein 24 hours before model establishment in miR-9-5p overexpression group and empty vector control group. The myocardial injury was observed by HE staining. The expression of miR-9-5p was detected by Real-time PCR. The serum levels of interleukin(IL)-6, tumor necrosis factor alpha(TNF-α), IL-1β, creatine kinase isoenzyme MB (CK-MB), cardiac troponin Ⅰ (cTnI), lactate dehydrogenase (LDH) and the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were measured were measured by ELISA. Cardiomyocyte apoptosis was detected by TUNEL. Double luciferase assay verified the relationship between miR-9-5p and TRPM7. The protein expressions of TRPM7, Bcl-2, Bcl-2 associated X (Bax), phosphorylated nuclear factor kappa-B 65 (p-NF-κB p65) and toll like receptor 4 (TLR4) were detected by Western blotting. Results The expression of miR-9-5p was low in myocardial tissue of rats (P<0.05). Overexpression of miR-9-5p could reduce the expression levels of CK-MB, cTnI and LDH, and improve the degree of myocardial injury. Compared with the model group, the apoptosis rate, Bax protein expression, MDA, IL-6, TNF-α and IL-1β contents in myocardial cells of miR-9-5p overexpression group decreased, while Bcl-2 protein expression and SOD content increased (P<0.05). The result of dual luciferase assay showed that TRPM7 was the target gene of miR-9-5p, and the protein expressions of TRPM7, p-NF-κB p65 and TLR4 in miR-9-5p overexpression group were lower than those in model group (P<0.05). Conclusion MiR-9-5p can inhibit myocardial cell apoptosis, oxidative stress and inflammation induced by myocardial ischemia-reperfusion, and inhibit TLR4/NF-κB pathway by regulating TRPM7.

The anaphase promoting complex (APC) regulates cell cycle progression by forming two functionally distinct E3 ubiquitin ligase complexes, APC^Cdc20 activated by cell division cycle protein 20 (Cdc20) and APC^Cdh1 activated by Cdc20 homologue 1 (Cdh1), respectively. Cdc20 and Cdh1 have different functions in the occurrence and development of the tumor. Cdc20 is a cancer promoter while Cdh1 suppresses tumorigenesis. Emerging evidence has begun to reveal that Cdc20 has positive functions in tumorigenesis, the overexpression of Cdc20 has been observed in many cancers. Currently, Cdc20 inhibitors, mostly non-specific inhibitors except apcin, not only block the combination between Cdc20 and APC, also block the combination between Cdh1 and APC, which leads to a poor selectivity. In this paper, the Cdc20 role in the development and process of cancers and its inhibitors are reviewed.

To evaluate the economics of Suhuang Zhike Capsules in the treatment of acute exacerbation of chronic obstructive pulmonary disease(AECOPD) for inpatients. Based on the published clinical research data, cost-utility analysis was used in this study to evaluate the pharmacoeconomics of Suhuang Zhike Capsules in treatment of AECOPD inpatients from the perspective of medical insu-rance. The test group was treated with Suhuang Zhike Capsules combined with conventional Western medicine, and the control group was treated with conventional Western medicine alone. Treeage software was used to construct a pharmacoeconomic model and perform simulation analysis. The results showed that the cost and output of Suhuang Zhike Capsules combined with the conventional Western medicine were 60 010.18 yuan and 1.92 quality adjusted life year(QALYs), respectively in the simulated 3 years of disease treatment. The cost and output of the conventional Western medicine were 96 730.60 yuan and 1.90 QALYs respectively. Suhuang Zhike Capsules combined with conventional Western medicine required lower cost but achieved higher output, showing cost-utility advantages, so this drug combination was a plan with pharmacoeconomic advantages. The sensitivity analysis results showed that the conclusion was relatively stable. Based on the above results, it is believed that as compared with the conventional Western medicine, Suhuang Zhike Capsules combined with conventional Western medicine have lower cost and higher output for the treatment of AECOPD inpatients, and it is a treatment plan with pharmacoeconomic advantages.
Capsules ; Drugs, Chinese Herbal/therapeutic use* ; Economics, Pharmaceutical ; Humans ; Inpatients ; Pulmonary Disease, Chronic Obstructive/drug therapy*

OBJECTIVEIn mid-July 2005, five patients presented with septic shock to a hospital in Ziyang city in Sichuan, China, to identify the etiology of the unknown reason disease, an epidemiological, clinical, and laboratory study were conducted.

METHODSAn enhanced surveillance program were established in Sichuan, the following activities were introduced: active case finding in Sichuan of (a) laboratory diagnosed Streptococcus suis infection and (b) clinically diagnosed probable cases with exposure history; supplemented by (c) monitoring reports on meningococcal meningitis. Streptococcus suis serotype 2 infection was confirmed by culture and biochemical reactions, followed by sequencing for specific genes for serotype and virulence factors.

RESULTSFrom June 10 to August 21, 2005, 68 laboratory confirmed cases of human Streptococcus suis infections were reported. All were villagers who gave a history of direct exposure to deceased or sick pigs in their backyards where slaughtering was performed. Twenty six (38%) presented with toxic shock syndrome of which 15 (58%) died. Other presentations were septicaemia or meningitis. All isolates were tested positive for genes for tuf, species-specific 16S rRNA, cps2J, mrp, ef and sly. There were 136 clinically diagnosed probable cases with similar exposure history but incomplete laboratory investigations.

CONCLUSIONAn outbreak of human Streptococcus suis serotype 2 infections occurred in villagers after direct exposure to deceased or sick pigs in Sichuan. Prohibition of slaughtering in backyards brought the outbreak to a halt. A virulent strain of the bacteria is speculated to be in circulation, and is responsible for the unusual presentation of toxic shock syndrome with high case fatality.

Animals ; Bacteremia ; epidemiology ; microbiology ; China ; epidemiology ; Disease Outbreaks ; Humans ; Meningitis, Bacterial ; epidemiology ; microbiology ; Shock, Septic ; epidemiology ; microbiology ; Streptococcal Infections ; epidemiology ; microbiology ; veterinary ; Streptococcus suis ; isolation & purification ; Swine ; Swine Diseases ; microbiology