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This study employed the α-glucosidase inhibitory activity model as an anti-diabetic assay and implemented a bioactivity-guided isolation strategy to identify novel natural compounds with potential therapeutic properties. Hypericum sampsoniiwas investigated, leading to the isolation of two highly modified seco-polycyclic polyprenylated acylphloroglucinols (PPAPs) (1 and 2), eight phenolic derivatives (3-10), and four terpene derivatives (11-14). The structures of compounds 1 and 2, featuring an unprecedented octahydro-2H-chromen-2-one ring system, were fully characterized using extensive spectroscopic data and quantum chemistry calculations. Six compounds (1, 5-7, 9, and 14) exhibited potential inhibitory effects against α-glucosidase, with IC50 values ranging from 0.050 ± 0.0016 to 366.70 ± 11.08 μg·mL-1. Notably, compound 5 (0.050 ± 0.0016 μg·mL-1) was identified as the most potential α-glucosidase inhibitor, with an inhibitory effect about 6900 times stronger than the positive control, acarbose (IC50 = 346.63 ± 15.65 μg·mL-1). A docking study was conducted to predict molecular interactions between two compounds (1 and 5) and α-glucosidase, and the hypothetical biosynthetic pathways of the two unprecedented seco-PPAPs were proposed.
Subject(s)
Molecular Structure , Hypericum/chemistry , alpha-Glucosidases , Magnetic Resonance Spectroscopy , Glycoside Hydrolase Inhibitors/pharmacologyABSTRACT
Objective:To investigate the short-term efficacy of laparoscopic total gastrec-tomy with hand-sewn esophagojejunostomy versus Roux-en-Y anastomosis.Methods:The propen-sity score matching and retrospective cohort study was conducted. The clinicopathological data of 159 patients who underwent laparoscopic total gastrectomy in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from October 2014 to July 2021 were collected. There were 107 males and 52 females, aged 63(range, 28?79)years. Of 159 patients, 71 cases undergoing totally laparoscopic total gastrectomy with hand-sewn esophagojejunostomy were allocated into totally laparoscopic group and 88 cases undergoing laparoscopic-assisted total gastrectomy with Roux-en-Y anastomosis were allocated into laparoscopic-assisted group, respectively. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative conditions; (3) perioperative complications. Propensity score matching was done by the 1:1 nearest neighbor matching method. Measurement data with normal distribution were expressed as Mean± SD, and t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M(range), and the Mann-Whitney U test was used for comparison between groups. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher's exact probability method. The rank sum test was used for comparison of ordinal data. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of 159 patients, 112 cases were successfully matched, including 56 cases in the totally laparoscopic group and 56 cases in the laparoscopic-assisted group. Before propensity score matching, age, cases with tumor located in cardia or gastric body in the totally laparoscopic group were 61(range, 30?76)years, 26, 45, respectively. The above indicators in the laparoscopic-assisted group were 65(range, 28?79)years, 50, 38, respectively. There were significant differences in the above indicators between the two groups ( Z=?2.89, χ2=6.43, P<0.05). After propensity score matching, the males and females, age, body mass index, cases of American Society of Anesthesiologists classification Ⅰ, Ⅱ, Ⅲ and Ⅳ, tumor diameter, cases with tumor located in cardia or gastric body, cases in TNM stage Ⅰ, Ⅱ and Ⅲ of patients in the totally laparoscopic group were 40, 16, (62±9)years, (22.7±2.8)kg/m 2, 22, 26, 7, 1, 3.5(range, 0.6?17.0)cm, 24, 32, 22, 9, 25. The above indicators of patients in the laparoscopic-assisted group were 38, 18, (62±10)years, (22.7±3.2)kg/m 2, 19, 32, 5, 0, 4.0(range, 0.6?15.0)cm, 23, 33, 21, 7, 28, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.17, t=?0.09, ?0.04, Z=?0.12, ?0.82, χ2=0.04, Z=?0.42, P>0.05). The elimination of age and tumor location confounding bias ensured comparability between the two groups. (2) Intraoperative and postoperative conditions: after propensity score matching, the total operation time, time of esophagojejunostomy, postopera-tive 24-hour pain numerical score and time to first out-off bed activities were (310±49)minutes, (37±10)minutes, 2.3±0.8 and (2.4±0.7)days for patients in the totally laparoscopic group, versus (344±77)minutes, (44±12)minutes, 3.1±1.2 and (2.9±1.0)days in the laparoscopic-assisted group, showing significant differences between the two groups ( t=?2.85, ?3.05, ?4.20, ?3.10, P<0.05). (3) Perioperative complications: after propensity score matching, 6 cases of the patients in the totally laparoscopic group had Clavien-Dindo grade 2 or higher complications, including 2 cases of anas-tomotic leak, 1 case of anastomotic stenosis, 1 case of pleural effusion, 1 case of abdominal infection and 1 case of intestinal obstruction. The incidence of Clavien-Dindo grade 2 or higher complications was 10.7%(6/56). In the laparoscopic-assisted group, 5 patients had Clavien-Dindo grade 2 or higher complications, including 2 cases of anastomotic leak, 1 case of abdominal infection, 1 case of intestinal obstruction and 1 case of cholangitis. The incidence of Clavien-Dindo grade 2 or higher complications was 8.9%(5/56). There was no significant difference in the incidence of Clavien-Dindo grade 2 or higher complications between the two groups ( χ2=0.10, P>0.05). Patients with anas-tomotic leak were improved after puncture and drainage, secondary surgery and conservative treat-ment, and other complications were improved after symptomatic treatment. Conclusions:Com-pared with Roux-en-Y anastomosis in laparoscopic total gastrectomy, the time of hand-sewn esophagojejunostomy and esophago-jejunal anastomosis are shorter, patients have less postopera-tive pain and faster postoperative recovery. Both methods have good peri-operative safety.
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Gastric cancer is one of the malignant tumors with high morbidity and high mortality in China.Research has shown that viral infection is closely related to the occurrence of gastric cancer.EpsteinBarr virus-associated gastric cancer characterized by EB virus infection has been classified as a subtype of gastric cancer,whose epidemiology,pathogenesis,clinical and histopathologic features have been studied in detail.At the same time,oncolytic viruses reveal the inhibitory effect of the virus on tumors,and their ability to target and kill tumor cells is used in the treatment of some advanced cancers.This article will review the research advances about relevance to gastric cancer of several viruses that have been reported and the latest progress in anticancer mechanisms and combined therapies for oncolytic viruses.
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Background: Aberrant Bcl-2 transcription is closely related with nodal diffuse large B-cell lymphoma (DLBCL), however, the relationship between Bcl-2 and primary gastrointestinal DLBCL (PGI-DLBCL) was not fully studied.Aims: To investigate the relationship between Bcl-2 gene amplification and protein expression and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL.Methods: Clinical data was collected from 136 PGI-DLBCL patients receiving surgical treatment, and a telephone interview was conducted for survival information.Bcl-2 gene amplification and protein expression in tumor tissue were determined by fluorescence in situ hybridization and immuno-histochemistry, respectively, and relationships between Bcl-2 and clinicopathological characteristics, immunophenotype and prognosis of PGI-DLBCL were analyzed.Results: Among 136 PGI-DLBCL patients, 33 (24.3%) showing gene amplification and 90 (66.2%) showing protein expression of Bcl-2;gene amplification was correlated with primary tumor location, Ann Arbor stage, serum lactate dehydrogenase level, B symptom and International Prognostic Index (IPI) score (P<0.05), while protein expression was correlated with primary tumor location and immunophenotype (P<0.05).5-year overall survival (OS) in patients positive for Bcl-2 gene amplification and patients with non-GCB immunophenotype and positive for Bcl-2 protein expression were inferior to those negative ones (41.5%vs.71.5%, P<0.05;54.6% vs.84.6%, P<0.05).In Bcl-2 gene amplification or protein expression positive patients, 5-year OS of CHOP chemotherapy was inferior to that of rituximab combined with CHOP chemotherapy (48.6%vs.80.3%, P<0.05;66.4%vs.83.4%, P<0.05).Conclusions: Detection of Bcl-2 gene amplification is useful for prediction of prognosis in PGI-DLBCL.Both patients with Bcl-2 gene amplification and non-GCB patients with Bcl-2 protein expression have a poorer prognosis.Rituximab may improve the prognosis in patients with Bcl-2 gene amplification or protein expression.
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Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions . Methods Retrospectively analyzed the contrast-enhanced ultrasound model and angiographic predictive model of 465 cases of the A prospective multicenter study of breast nodules contrast-enhanced ultrasound" that led the Sichuan Provincial People′s Hospital from January 2016 to April 2017 ,which included 69 cases of breast precancerous lesions and 396 other types benign lesions ,and the sensitivity ,specificity and accuracy of the diagnosis of breast precancerous lesions were calculated . Results The sensitivity of ultrasound predictive model for the diagnosis of precancerous lesions was 60 .9％ and AUC was 0 .681 . Precancerous lesions mainly showed non-concentricity , increased homogeneity , and increased lesions;other types of benign lesions mainly showed non-centripetal ,high uniformity enhancement and lesion size unchanged . Conclusions Contrast-enhanced ultrasound shows a potential value in the differential diagnosis of precancerous lesions and other types of benign lesions ,that can help clinicians to take early intervention measures for breast precancerous lesions ,but there are still many problems to be solved .
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Objective To explore the protective effect and mechanism of exogenous hydrogen sulfide ( H2 S) on pressure ulcer rats with ischemia/reperfusion ( I/R) injury. Methods Forty SD rarts were randomly divided into 4 groups,namely normal control group,I/R model group,low-dose H2 S intervention group and high-dose H2 S interven-tion group. Each group had 10 animals. The low-and the high-dose H2 S intervention groups were injected intraperitone-ally 10 and 30μmol/kg of sodium hydrosulfide ( NaHS) for 1 week,respectively;however,the normal control group and I/R model group were treated with same volume 9 g/L saline. Then,the normal control group did not sustain any pres-sure,but other 3 groups were pressurized. After 3 circulations of ischemia/reperfusion,all rats were sacrificed,and path-ological changes in pressure ulcer rats were evaluated by HE staining. Serum H2 S contents were analyzed through meth-ylene spectrophotometric method. Serum levels of tumor necrosis factor-α(TNF-α),interleukin-6 (IL-6),intercellu-lar adhesion molecule -1 (ICAM-1),and myeloperoxidase (MPO) were detected by enzyme linked immunosorbent assay ( ELISA ) . The activities of malondialdehyde ( MDA ) , superoxide dismutase ( SOD ) , glutathione-peroxidase ( GSH-Px) and catalase ( CAT) in the homogenate of muscle were examined. Apoptotic index ( AI) was calculated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL) . The expressions of Bcl-2 and Bax in muscle tissue were evaluated by Western blot. Results In comparison with the normal control group,serum TNF-α, IL-6,ICAM-1 and MPO levels,MDA activity in the homogenate of muscles,AI and Bax expression level were in-creased (all P<0. 01),while serum H2S levels,the activities of SOD,GSH-Px and CAT as well as Bcl-2 expression levels were reduced in the I/R model group (all P<0. 01). Upon intervention therapy of low-or high-dose H2S,path-ological scores,serum TNF-α,IL-6,ICAM-1 and MPO levels,MDA activity in the homogenate of muscle,AI and Bax expression levels were gradually reduced while serum H2 S levels,the activities of SOD,GSH-Px and CAT and Bcl-2 expression levels were gradually enhanced when compared to those of the I/R model group (all P<0. 05,0. 01). Con-clusions Exogenous H2 S has better protection against pressure ulcer rats with I/R injury. The mechanism may be as-sociated with inhibition of inflammatory reaction and enhancement of antioxidative ability as well as reduction of apopto-sis.
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Objective We tried to explore the effects of organ donation intervention on organ donation knowledge,attitude and willingness of community residents and analyze its promotive factors,thereby to provide valuable basis to increase organ donation rate.Methods 354 community residents in Hengyang city of Hunan province were randomly collected and received organ donation intervention.The scores of organ donation knowledge,attitude and willingness,living organ (bone marrow and kidney) donation willingness rate,and supporting relative organ donation status were compared before and after intervention.We also investigated the factors that could enhance organ donation.Results In comparison with before intervention,organ donation knowledge and willingness scores(t value was 4.46 and 5.13),bone marrow donation willingness rate (x2 value was 9.27) and supporting relative organ donation proportion(x2 value was 10.74) were increased,but organ donation attitude score was decreased in community residents.However,organ donation intervention had no effect on kidney donation willingness rate.Community residents recognized that economic compensation (43.68％),organ distributing fair (23.85％) and consummate organ donation regime (11.21％) were the most important to facilitate organ donation.Conclusions Organ donaton intervention can notably improve organ donation knowledge,attitude and willingness of community residents.Moreover,giving determinate economic compensation,ensuring organ distributing fair and ameliorating organ donation regime may play key roles in relieving current organ shortage crisis.
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Objective To compare the clinical efficacy of Freka trelumina (FT) vs.feeding jejunostomy (FJ) in carrying out postoperative early enteral nutrition (EEN) in old patients with gastric cancer.Method 168 old gastric cancer cases were derided into FT group (n =54) with EEN, FJ group (n =50) with gastric tube and EEN, and total parenteral nutrition (TPN) group (n =64).Results Compared with TPN group, postoperative body weight, serum albumin and prealbumin level in FT and FJ groups were significantly higher, intestinal function recovery time, days of postoperative hospitalization and costs were significantly lower.The incidence of cough, sputum and sore throat of patients in FT group were significantly higher than those in FJ and TPN groups (P ＜ 0.05).Conclusions Postoperative EEN through FT and FJ was effective to improve nutritional parameter, accelerate intestinal function recovery, reduce the number of days of postoperative hospitalization, total costs, anastomotic stomal leak and gastroparesis rate.
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Objective To analyze the clinico-pathological characteristics and prognostic factors of patients with gastric neuroendocrine carcinoma(G-NEC).Methods Clinical data of 40 cases of G-NEC form January 2003 to August 2013 at Ren Ji Hospital of Shanghai Jiaotong University were analyzed.Tumors were classified into different grades and stages according to the 2010 WHO classification and the 2006 European neuroendocrine tumor society (ENETS).Follow-up was conducted by telephone.The survival curves were drawn using Kaplan-Meier method.Univariate analysis was performed by the Log-rank test and multivariate analysis was performed by the COX proportional hazards model.Results Among the 40 G-NECs patients,29 were male(72％) and 11 were female(28％),with an median age of 61 years.Tumors located in the gastric cardia in 20 cases,in the gastric antrum in 11 cases and in the gastric body in 9 cases.Tumor ranged from 1 cm-20 cm.All patients were G-NEC (G3).Follow-up rate was 100％ (40/40).The median overall survival rate was 12 months,and one-year survival rate was 82％.Immunohistochemically G-NEC cells were positive for CgA and Syn in 11 cases.Gender (x2 =5.673,P ＜ 0.05),Ki-67 index (x2 =8.612,P ＜ 0.05),and lymphnode involvement (x2 =0.559,P ＜ 0.05) were prognostic factors of G-NEC patients.Conclusions The symptoms of G-NEC are nonspecific.Its diagnosis relies on pathological examination and immunohistochemistry.Syn and CgA are the most important markers.Female gender,lower Ki-67 index and lower lymph node metastasis predict a survival advantage.
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Objective To investigate the relationship between tumor subclassifieation and the clinicopathologic features and prognosis of patients with gastrointestinal diffuse large B-cell lymphoma (DLBCL). Method From June 2000 to June 2007, 63 gastrointestinal DLBCL cases were enrolled. Immunohistochemical staining was performed to detect CDIO, Bcl-6 and MUM1 expression. Tumors were subclassified according to CDIO, Bcl-6 and MUM1 expression. Results CD10 expression was positive in 13 cases. Bcl-6 expression was positive in 53 cases. MUM1 expression was positive in 52 cases. According to the expression of CD10, Bcl-6 and MUM1, 17 cases(27%) were of germinal center B cell-like (GCB) DLBCL and 46 cases (73%) were of non-GCB. There was a significant difference in local lymph node metastasis between GCB group and non-GCB group, but there was no significant difference in terms of tumor size and infiltrate depth between the two subgroups. The survival time of patients in GCB group(76 months) was significantly longer than that of non-GCB group (28 months). Among cases receiving postoperative chemotherapy (CHOP), the survival of GCB group (76 months) was longer than non-GCB group (24 months). All 4 GCB cases and 4 non-GCB cases under R-CHOP chemotherapy are alive (22 ～ 47 months). Conclusion Gastrointestinal DLBCL subclassification is closely correlated with local lymph node metastasis, and this in combination with the expression of CD10 could be used to predict the prognosis of patients with gastrointestinal DLBCL.