Quercetin attenuates lipopolysaccharide-induced hepatic inflammation by modulating autophagy and necroptosis.

Lipopolysaccharide (LPS) from Gram-negative bacteria initially induces liver inflammation with proinflammatory cytokines expressions. However, the underlying hepatoprotective mechanism of quercetin on LPS-induced hepatic inflammation remains unclear. Specific pathogen-free chicken embryos (n = 120) were allocated control vehicle, PBS with or without ethanol vehicle, LPS (125 ng/egg) with or without quercetin treatment (10, 20, or 40 nmol/egg, respectively), quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated abovementioned solutions via the allantoic cavity. At embryonic d 19, the livers of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, and immunohistochemistry investigation. We found that the liver presented inflammatory response (heterophils infiltration) after LPS induction. The LPS-induced mRNA expressions of inflammation-related factors (TLR4, TNFα, IL-1ß, IL-10, IL-6, MYD88, NF-κB1, p38, and MMP3) were upregulated after LPS induction when compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. Quercetin significantly decreased the immunopositivity to TLR4 and MMP3 in the treatment group when compared with the LPS group. Quercetin could significantly downregulate the mRNA expressions of autophagy-related genes (ATG5, ATG7, Beclin-1, LC3A, and LC3B) and necroptosis-related genes (Fas, Bcl-2, Drp1, and RIPK1) after LPS induction. Quercetin significantly decreased the immunopositivity to LC3 in the treatment group when compared with the LPS group; meanwhile, quercetin significantly decreased the protein expressions of LC3-I, LC3-II, and the rate of LC3-II/LC3-I. In conclusions, quercetin can alleviate hepatic inflammation induced by LPS through modulating autophagy and necroptosis.

Retraction: Salidroside inhibits the proliferation and migration of gastric carcinoma cells and tumor growth via the activation of ERS-dependent autophagy and apoptosis.

[This retracts the article DOI: 10.1039/C9RA00044E.].

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Risk factors of secondary infection/recurrence after ablation for liver cancers: A systemic review and meta-analysis.

Background: This study aimed to systemically explore the risk factors of secondary infection/recurrence after ablation in patients with liver cancer. Methods: Relevant literature in PubMed, EMbase, and Cochrane Library databases were searched with keywords including "liver cancer or carcinoma," "ablation," "infectious or infection or recurrence," and "risk factor or relevant factor or correlative factor or influencing factor." Meta-analyses were performed and forest plots were drawn for risk factors, including the tumor size and location, number of tumor nodules, hepatitis B virus (HBV) DNA levels, serum alpha fetal protein (AFP) levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy. A funnel plot was drawn to assess the publication bias. Results: A total of 23 studies were included from the initial 701 potentially relevant articles. Our meta-analyses showed that a large tumor size (odds ratio [OR] = 1.58; 95% confidence interval [CI]: 1.31-1.92); proximity to the colon, large vessels, and large hepatic vein (OR = 4.10; 95% CI: 2.26-7.43); multinodular tumor (OR = 2.10; 95% CI: 1.46-3.03), the higher HBV DNA levels (OR = 1.34; 95% CI: 1.09-0.64); higher serum AFP levels (OR = 1.56; 95% CI: 1.18-2.05), lower serum albumin levels (OR = 1.67; 95% CI: 1.06-2.65); Child-Pugh Class B and Class C (OR = 1.27; 95% CI: 1.05-1.54); and lack of antiviral therapy (OR = 1.75; 95% CI: 0.93-3.28) were associated with an increased risk of post-ablation infection/recurrence in patients with liver cancers. Conclusion: Our results indicated that the tumor size and location, number of tumor nodules, HBV DNA levels, serum AFP levels and serum albumin levels, Child-Pugh Class, and lack of antiviral therapy were the risk factors for post-ablation infection/recurrence in patients with liver cancer. Here, we have provided directions for the clinical prevention of secondary infection/recurrence in patients with liver cancer who underwent ablation therapy.

Application of Moorehead-Ardelt Questionnaire Ⅱ in evaluation of quality of life among patients after bariatric surgery / 中华普通外科杂志

Objective:To evaluate the application of Moorehead-Ardelt Ⅱ questionnaire (MA Ⅱ) in assessment of the quality of life (QOL) among obese patients after bariatric surgery.Methods:One hundred and five patients with obesity were enrolled, the weight, body mass index (BMI), comorbidities and MA Ⅱ scores before and after operation were counted. The difference between the QOL of pre- and post-operation was analyzed.Results:All the patients completed the questionnaire. The Cronbach α coefficient of the questionnaire was higher than 0.7. The post-operational scores of 6 items were significantly higher than that of pre-operation. ( P<0.001). The proportion of "poor" and "very poor" QOL in the pre-operational patients was 43.8%, compared with 0 in the post-operative patients;the proportion of "good" and "very good" QOL in the pre-operatve patients was 4.7%, compared to 86.7% in the post-operative patients ( χ2=146.863, P<0.001). Conclusions:MA Ⅱ questionnaire is a professional, easy oprated tool for assessment of QOL associated with obesity.

LncRNA LINC00689 Promotes the Progression of Gastric Cancer Through Upregulation of ADAM9 by Sponging miR-526b-3p.

INTRODUCTION: Increasing studies have demonstrated that noncoding RNAs, including miRNAs and lncRNAs, have vital roles in mediating cancer progression. However, the expression features and biological functions of LINC00689 in gastric cancer (GC) remain largely unknown. This study was designed to investigate the functions of LINC00689, miR-526b-3p and ADAM9 as well as their interactions in GC. METHODS: Real time PCR(RT-PCR) was used to detect the expression of LINC0068, miR-526b-3p and ADAM9 in both GC tissues or cell lines. Gain- and loss- of functions of assays were conducted to verify the role of LINC0068, miR-526b-3p and ADAM9 in GC development. Cell proliferation were determined by CCK8 assay and transwell assay and scratch wound-healing assay were used to test cell invasion and migration. Further, the relationships between LINC00689 and miR-526b-3p, miR-526b-3p and ADAM9 were predicted by bioinformatics analysis and then proved by Luciferase reporter assay and RNA Immunoprecipitation(RIP) assay. RESULTS: We found that LINC00689 was upregulated in GC tissues and positively correlated with advanced tumor stage and tumor size, while miR-526b-3p was downregulated. Furthermore, gain- and loss-of-function experiments revealed that LINC00689 promoted the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells, while miR-526b-3p had the opposite effects. The underlying mechanisms indicated that LINC00689 functioned as a competing endogenous RNA (ceRNA) by sponging miR-526b-3p in GC cells. Further investigations confirmed that ADAM9 was a direct target of miR-526b-3p and positively modulated the progression of GC. CONCLUSION: Our study suggests that LINC00689 functions as a novel oncogenic lncRNA in the development of GC by promoting ADAM9 expression through suppression of miR-526b-3p.

Preoperative lymphocyte to monocyte ratio predicts lymph node metastasis in gastric cancer / 中华普通外科杂志

Objective:To investigate the predictive value of preoperative peripheral blood lymphocyte to monocyte ratio (LMR) for lymph node metastasis in gastric cancer.Methods:Data of 177 gastric cancer patients who underwent surgical treatment in Beijing Shijitan Hospital from Jan 2014 to May 2017 were retrospectively analyzed. According to the ROC curve, the optimal critical value is determined to be 3.79. By this value, patients were divided into high LMR group (LMR≥3.79) and low LMR group (LMR<3.79). Patients′ clinicopathological characteristics were collected to analyze the relationship between LMR and lymph node metastasis and lymph node N staging.Results:A comparison of LMR and N1 and N2 stage between the two groups showed no significant difference, but both N1 and N2 had statistical defference with N3 ( P<0.05), suggesting a positive correlation between low LMR and high N stage. Logistic regression analysis proves that low LMR is significantly correlated with metastatic lymph node when the number was more than 6. Conclusion:Low LMR is positively correlated with lymph node metastasis in gastric cancer patients.

Salidroside inhibits the proliferation and migration of gastric carcinoma cells and tumor growth via the activation of ERS-dependent autophagy and apoptosis.

The endoplasmic reticulum stress (ERS)-induced autophagy and apoptosis are favorable for the suppression of many cancer types. Salidroside (Salid) has been proven to be capable of inducing the apoptosis of many cancer cells. However, the underlying mechanisms and whether Salid can activate the autophagic system have still not been explained thoroughly. Herein, the inhibition effect of Salid on the growth and progress of gastric cancer and the underlying mechanisms were investigated. With the SGC-7901 cells acting as the cancer model cells, we ascertained that Salid exerted a superior antagonism effect on the growth and migration of gastric cancer cells in a dose-dependent manner. Additionally, Salid exhibited strong capacity to induce cell apoptosis by the down-regulation of proliferation-related genes (Ki67 and PCNA), increase in the pro-apoptotic protein C-caspase-3, and changing the levels of other related genes. A mechanism study revealed that the levels of the ERS-related genes, such as CHOP, C-caspase-12, GADD34, and BiP, in the SGC-7901 cells dramatically changed post-treatment by Salid, indicating the involvement of ERS in Salid-inducing cell apoptosis. In addition, the increased LC3+ autophagic vacuoles, enhanced conversion of LC3-I to LC3-II, and inhibition of the PI3K/Akt/mTOR pathway further confirmed the activation of autophagy induced by Salid. Importantly, the effect of Salid in regulating the levels of autophagy-related proteins or the signaling pathway could be markedly depressed by co-incubating with Wortmannin (Wort), an autophagy inhibitor. The final evaluation of the tumor therapy efficacy exhibited satisfactory cancer growth inhibition by Salid with negligible toxicity to normal tissues. In summary, the present work provides a comprehensive effective evaluation of Salid for treating gastric cancer. The detailed investigation of the underlying mechanisms may offer a rational reference for the future applications of Salid in clinic.

Effect of laparoscopic sleeve gastrectomy on obesity and type 2 diabetes mellitus / 中华普通外科杂志

Objective To explore the morbidity of surgery in connection with laparoscopic sleeve gastrectomy (LSG) and its effect on obese T2DM.Methods 106 obese T2DM patientes undergoing LSG were divided into 2 groups in group 125 patients did not have oversewing the staple line and group 281 patients had the staple line oversewn in order to reduce bleeding.Results The differences in intraoperative blood loss (35 ± 15) ml vs.(28 ± 18) ml,postoperative recovery time (2.4 ± 0.9) d vs.(2.3 ± 0.9) d,time to taking liquid food (4.7 ± 1.0) d vs.(4.6 ± 1.0) d between two groups were not significant.There were no significant difference of complication between 2 groups (x2 =3.271,P =0.071).Comparing before surgery to 6 month after surgery,the BMI in group 1,was from (39 ± 5) to (29 ±4) kg/m2;in group 2,from (40 ±6) to (31 ±5) kg/m2,FPG in group 1,from (8.4 ± 1.4) to (6.4 ±1.2) mmol/L;in group 2,from (8.2 ± 2.0) to (6.8 ± 1.5) mmol/L,2 hour post-meal blood sugar [group 1,(13.2±4.1) to (9.6±3.2) mmol/L;group 2,(12.2±3.2) to (10.6±2.8) mmol/L] and HbAlc (group 1,7.2％ ±1.2％ to5.5％ ±1.1％;group 2,7.1％ ±1.1％ to 5.9％ ±1.2％) decreased significantly in both groups (P ＜ 0.01).There was 72 (68％) remission cases of T2DM in 106 patients,there were no significant differences of T2DM remission and BMI between 2 groups at 6 months after surgery (P =0.617).Conclusions LSG leads to significant weight loss and T2DM control.

A randomized controlled trial on two approaches in single lateral endoscopic thyroidectomy / 中华普通外科杂志

Objective To explore the application of different approaches in single lateral endoscopic thyroidectomy.Methods Ninety one patients with single lateral thyroid nodule who underwent endoscopic thyroidectomy were divided randomly into bilateral axillo-breast approach group (n =45) and transaxillary approach group (n =46).The clinical data and cosmetic outcomes were compared.Results Procedures were successfully performed in 86 patients with no conversion to open surgery,5 patients in transaxillary group were excluded because of the malignant frozen pathology.The total operation time of transaxillary approach group was (61.6 ± 4.9) min,significantly shorter than that of the bilateral axillo-breast approach approach (90.0 ± 6.5) min,P ＜ 0.05.There was no significant difference in time of subcutaneous tunnel construction,muscles disposal,lateral dissection,lower pole resection,parathyroid identification,thyroid lobe resection and bleeding volume between two groups (P ＞ 0.05),while the time of work space creation,upper pole resection in transaxillary approach was significantly shorter than that in the bilateral axillo-breast approach (P ＜ 0.05).All patients of both groups were satisfied with cosmetic results.Conclusions The operation time in transaxillary approach group was shorter than that in bilateral axillo-breast approach group for the single lateral thyroid nodule,but the operation was more difficuh.

Effects of pneumoperitoneum of laparoscopic cholecystectomy on the coagulation system of patients: a prospective observational study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Laparoscopic cholecystectomy has been widely used in clinical practice during the recent decades; however, the effects of pneumoperitoneum and the surgery on the coagulation system are largely unknown. This clinical study aimed to observe any possible effects of pneumoperitoneum and the surgery on the coagulation system of patients.</p><p><b>METHODS</b>This was a prospective observational study. The inclusion criteria included (1) patients with chronic cholecystitis and/or cholecystic polyps and (2) patients in the relief stage of acute cholecystitis. The exclusion criteria included (1) patients in the episodic stage of acute cholecystitis and those complicated with cholangiolithiasis; (2) patients with concomitant hematologic diseases, damages to the liver function, malignant tumors or immune system diseases, or patients complicated with thrombotic or hemorrhagic disorders; and (3) patients who had taken anticoagulant medication within a week before surgery. Fifty patients who were hospitalized into our department for elective laparoscopic cholecystectomy between November 2011 and February 2013 were eligible and enrolled into this study. Of the 50 patients, 22 were male and 28 female. The age of the patients ranged from 29 to 78 (mean 56.7±11.5) years. The surgery for each of the 50 patients was performed with the same equipment and conditions. The surgeries for all the patients were performed under general anesthesia with the patients in a 30-degree head-up tilted posture, and the pressure of pneumoperitoneum was maintained at 13 mmHg. Venous blood specimens were taken from each patient before and at the end of pneumoperitoneum (i.e., 0 hour after surgery) and at 8 hours after surgery for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), thrombin time (TT), and D-dimer (DD). The results of the determinations of these parameters were compared.</p><p><b>RESULTS</b>(1) All the patients recovered well without any complications. (2) The pre-pneumoperitoneum values of the parameters of coagulation had normalized. (3) The PT values slightly increased (P > 0.05) at the end of pneumoperitoneum (i.e., 0 hour after surgery) and decreased by 0.5 seconds at 8 hours after surgery as compared to the pre-pneumoperitoneum values (P < 0.05). (4) APTT at 0 and 8 hours decreased by 1.4 seconds (P > 0.05) and 3.7 seconds (P < 0.05) respectively as compared to pre-pneumoperitoneum values, while the difference between the APTT values at 0 and 8 hours after surgery was not statistically significant (P > 0.05). (5) FIB determined at 0 hour post-operation increased by 0.1 g/L as compared to pre-pneumoperitoneum values (P > 0.05); however, the FIB values at 8 hours after operation increased by 1.2 g/L as compared to the pre-pneumoperitoneum values (P < 0.05), and increased by 1.1 g/L as compared to 0 hour post-operation (P < 0.05). (6) The TT values obtained at 0 and 8 hours post-operation were not significantly different as compared to the pre-pneumoperitoneum values (P > 0.05). (7) The DD values gradually increased after operation; as compared to pre-pneumoperitoneum values, DD at 0 and 8 hours after operation increased by 210.8 ng/ml and 525.9 ng/ml respectively (P < 0.05) and DD at 8 hours after operation increased by 315.1 ng/ml as compared to 0 hour post-operation (P < 0.05).</p><p><b>CONCLUSIONS</b>The pneumoperitoneum for laparoscopic cholecycstectomy may lead to postoperative hypercoagulation in the patients, and thereby may increase the risks for development of postoperative thrombosis; Patients may have risks for occurrence of thrombosis within 8 hours after the operation, to which attention should be paid in favor of preventing thrombosis.</p>

Larporoscopic Roux-en-Y gastric bypass by different anastomoses for the treatment of type 2 diabetes mellitus / 中华普通外科杂志

ObjectiveTo evaluate treatment of type 2 diabetes mellitus (T2DM) by laparoscopic Roux-en-Y gastric bypass (LRYGB) using different amastomoses. MethodsTwenty one T2DM patients were divided into two groups:transoral EEA (OrVil) and Endo-GIA according to ways of gastrointestinal anatomosis andunderwentLRYGB. Clinicaldataincluding outcomeof operation, complications,preoperative and postoperative oral glucose tolerance test (OGTT),Homa-IR,Homa-β,blood lipid and nutrition status were analyzed.ResultsLRYGB procedures were successfully performed in all the 21 patients with no conversion to open surgery.The difference of intraoperative blood loss,postoperative recovery time between two groups was not significant.The mean operation time in OrVil group ( 126 ± 29 )mins was shorter than that in Endo-GIA group ( 156 ± 28 ) mins ( P ＜ 0.05 ),but at the same time,the mean expenditure was higher. Evaluated on three months after operation,the T2DM cure rate was 78％,and effective rate was 100％ in OrVil goup and those were 83％,100％ respectively in Endo-GIA group.No postoperative malnutrition, anemia or severe complication occurred.ConclusionsThe efficiency of laparoscopic Roux-en-Y gastric bypass using different amastomoses was same in the treatment of type 2 diabetes mellitus.The operation time was shorter in OrVil group but the expenditure was higher.

Technical difficulties and avoidance of complications in delayed laparoscopic cholecystectomy for acute cholecystitis / 中华肝胆外科杂志

Objective To investigate the technical difficulties and the avoidance of complications in delayed laparoscopic cholecystectomy (LC) for acute cholecystitis (AC).MethodsThe results of LC carried out on 133 consecutive patients with AC between February 2004 and August 2008 were retrospectively studied.The outcomes were compared between patients who received LC for AC within 72 hours (the early group) and those after 72 hours (the delayed group).There were 34 patients in the early group and 99 in the delayed group.During LC,Calot's triangle was carefully dissected,and the relationship of the cystic duct to the CBD and common hepatic duct was clearly identified.Retrograde cholecystectomy in 2 patients was used when the Calot's triangle was poorly identified.Laparoscopic subtotal cholecystectomy was carried out in 4 patients whose inflammation or fibrosis precluded dissection of the Calot's triangle.ResultsThere was no conversion to open cholecystectomy,biliary tract injury,biliary leak,or any other intraoperative or postoperative complications.There was no 30day readmission in the 2 groups.Patients who received delayed LC had a significantly longer operation time [(44.1±5.32) vs (66.4±3.05)rnin,P＜0.01].There was no significant difference in wound infection rates in the 2 groups (1/34 2.94 ％ vs 2/99 2.02 ％,P＞0.05).ConclusionsDelayed LC was as feasible and safe as early LC in the treatment of AC.Delayed LC was technically more demanding than early LC.