A Modified Purse-String Stapling Technique for Intracorporeal Circular Stapled Esophagojejunostomy During Laparoscopic Total Gastrectomy: Comparison with Extracorporeal Reconstruction Technique.

Background: Intracorporeal esophagojejunostomy (EJ) in the context of laparoscopic total gastrectomy remains a complex and technically demanding procedure. We have previously introduced a novel method of intracorporeal circular stapled EJ utilizing a conventional purse-string suture instrument. Since May 2018, we have refined this technique, and the aim of this study was to assess its safety and efficacy. Methods: Between May 2018 and June 2022, we enrolled 92 patients who underwent laparoscopic total gastrectomy with the modified intracorporeal reconstruction method. In addition, between March 2014 and June 2022, we enrolled 121 patients who underwent the procedure with the extracorporeal reconstruction method. We retrospectively collected and compared the clinical data of these 2 patient cohorts. Results: Intracorporeal reconstruction group experienced lower postoperative pain scores (2.7 ± 1.3 versus 4.5 ± 1.4, P = .032), reduced administration of analgesics (3.1 ± 2.2 versus 5.0 ± 3.5, P = .041), and shorter postoperative hospital stays (4.9 ± 2.3 versus 6.3 ± 3.5, P = .045) compared with the extracorporeal reconstruction group. In addition, anastomotic time and postoperative pain score were not increased in the overweight patients in the intracorporeal reconstruction group. Anastomotic leakage occurred in 2 (2.2%) patients in the intracorporeal reconstruction group and 4 (3.3%) patients in the extracorporeal reconstruction group. Anastomotic stricture occurred in 1 (1.1% and 0.8%) patient in each group. There was no significant difference in the overall postoperative complication rate between the 2 groups. Conclusions: The modified intracorporeal purse-string stapling technique for EJ during laparoscopic total gastrectomy is a safe and viable option, exhibiting less invasiveness and comparable outcomes to the extracorporeal reconstruction method, especially suitable for obese patients.

Intracorporeal Circular Stapled Esophagojejunostomy Using Conventional Purse-String Suture Instrument After Laparoscopic Total Gastrectomy.

BACKGROUND: An optimal alimentary tract reconstruction technique after laparoscopic total gastrectomy (LTG) remains controversial. The authors developed a new simple technique for intracorporeal esophagojejunal anastomosis that employs a conventional purse-string suture instrument (PSI) and circular stapler. METHODS: From May 2014 to April 2016, 41 consecutive patients with gastric cancer underwent LTG in the author's institution. Intracorporeal esophagojejunal anastomosis using the following method was attempted for all patients. After total gastrectomy was completed laparoscopically, a small vertical incision (about 40 mm) was created at the left midclavicular line and retracted by a wound retractor. An anvil of a 25 mm circular stapler was introduced into the abdominal cavity. Then a previously prepared surgical glove, which was cut open at the thumb and the little finger through which the two hand shafts of the PSI were passed separately and sealed by ties, was attached to the wound retractor to maintain airtightness, and the PSI was introduced into the abdominal cavity. The following procedure was similar to conventional open surgery except that it was performed under laparoscopic vision. RESULTS: Intracorporeal esophagojejunal anastomosis was performed successfully for all 41 patients. No case required extension of the initial incision for difficulties during anastomosis. The mean operation time was 245 minutes, and the mean time for the purse-string suture and anvil placement was 15 minutes. Tumor-free margins were achieved in all 41 patients. There were no anastomosis-related complications or other major surgical complications. CONCLUSIONS: With the described method, intracorporeal esophagojejunal anastomosis can be performed easily and safely.

Effects of the modified electric convulsive treatment (MECT) on cell factors of schizophrenia.

The expression of cell factors of schizophrenia and the effect of the modified electric convulsive treatment (MECT) were studied. In total, 156 patients with schizophrenia were selected, and divided into the drug group (70 cases) and the drug combined with MECT group (combined group) (86 cases) according to the treatment methods. In addition, 70 cases of healthy volunteers (control group) were selected according to the closest matching method based on 1:1 of age and gender. The drug treatment, consisted of anti-psychotic drugs, such as risperidone 2-8, quetiapine 300-750, ziprasidone 80-160 or aripiprazole 10-30 mg/day, and for the control group, we used the electric spasm therapeutic instrument, Thymatron®IV Systems up to 6 times, 3 times a week. The levels of interleukin (IL)-10, IL-4, IL-6 and IL-1 were detected before and after treatment by ELISA. The positive and negative symptom scale (PANSS) was used to evaluate the efficiency. Before the treatment, IL-1 and IL-6 levels of drug and combined groups were significantly higher than those of the control group (P<0.05), while IL-4 and IL-10 had no difference with the control group. There was no significant difference of each factor between the drug and combined groups. After treatment, IL-1, IL-6 and IL-10 of the drug group did not change compared to the levels before treatment, but IL-4 increased significantly; IL-1 and IL-10 of the combined group did not change, while IL-4 and IL-6 increased significantly; IL-1, IL-4 and IL-6 of the drug and combined groups were significantly (P<0.05) higher than those in the control group, but not IL-10. IL-1, IL-4 and IL-6 levels of the combined group were significantly higher (P<0.05) than those of the drug group. After treatment, the PANSS scores of the two groups decreased and the combined group decreased more significantly (P<0.05). The reduction rate of the combined group was significantly higher (P<0.05) than that of the drug group. The total efficiency of the combined group was significantly higher than that of the drug group, and after comparing these levels, there was statistical significance (P<0.05). IL-1, IL-4, IL-6 and IL-10 levels of the drug and combined groups before treatment were not associated with PANSS scores and the variation of IL-1, IL-4, IL-6 and IL-10 of the drug and combined groups had no correlation with the reduction rate of the PANSS. The results showed that, cell factors of schizophrenia had an abnormal expression, and medication and MECT can affect the expression level. In addition, MECT can improve the effect in the treatment of schizophrenia, but had no obvious correlation with the change of cell factors.

Novel hydroxybutyl chitosan nanoparticles for siRNA delivery targeting tissue factor inhibits proliferation and induces apoptosis in human vascular smooth muscle cells.

Chitosan, a polysaccharide isolated from shrimp and other crustacean shells, has been widely investigated for DNA and siRNA delivery. Despite substantial effort having been made to improve chitosan as a non­viral gene delivery vector, the application is severely limited by its poor solubility under physiological conditions. Hydroxybutyl chitosan (HBC), a modified chitosan, is soluble under neutral conditions. Tissue factor (TF) is involved in the pathogenesis of cardiovascular diseases by promoting thrombus formation and inducing the migration and proliferation of vascular smooth muscle cells. Targeting TF is an attractive therapeutic strategy for cardiovascular diseases. In the present study, the use of HBC for the transfer of TF­siRNAs into human umbilical vein smooth muscle cells (HUVSMCs) was investigated, and the effects of TF knockdown on cell proliferation and apoptosis were examined. HBC/siRNA nanoparticles were produced by mixing HBC and siRNA solutions with the assistance of tripolyphosphate buffer. The transfection efficiency with these nanoparticles was 74±2.5%, which was determined using a fluorescence­labeled siRNA under fluorescence microscopy. The delivery of HBC/TF­siRNA resulted in reductions in the production of cellular and soluble TF protein in HUVMSCs, which were measured using western blotting and enzyme­linked immunosorbent assay, respectively. TF knockdown led to inhibited cell proliferation, as assessed using a Cell Counting Kit­8 assay, and increased cell apoptosis, determined using Annexin V­fluorescein isothiocyanate staining. These findings suggested that HBC may be a promising vector for siRNA delivery, and that in vivo HBC/siRNA nanoparticle delivery targeting TF may be a potential option for the treatment of cardiovascular diseases, which warrants further investigation.

Plasma nesfatin-1 level in obese patients after acupuncture: a randomised controlled trial.

BACKGROUND: Nesfatin-1 is an anorexigenic hormone suggested to regulate obesity. OBJECTIVE: To investigate the relationship between nesfatin-1 level and anthropometric and metabolic parameters in obese patients, and examine the change in plasma nesfatin-1 level after acupuncture treatment. METHODS: 64 obese adult patients without diabetes and 58 normal weight control subjects were enrolled in this study. The obese patients were randomly divided into an acupuncture plus diet group (n=32) and a diet only group (n=32). Measurements were repeated after 45 days. RESULTS: Body mass index (BMI), waist and hip circumferences, serum insulin, lipoprotein and insulin resistance measures were significantly higher, and plasma nesfatin-1 level was significantly lower, in obese patients than in normal weight controls. In addition, negative correlations were found between plasma nesfatin-1 level and BMI, waist and hip circumferences. Weight reduction in participants after acupuncture and diet restriction was 7.0% and 4.3%, respectively. Plasma nesfatin-1 level increased from 2.75±1.16 to 3.44±1.28 ng/mL and from 2.86±1.07 to 3.23±1.06 ng/mL in acupuncture and diet groups, respectively; the difference was significant, p<0.05. CONCLUSIONS: Plasma nesfatin-1 level is reduced in obese adults, and is increased after acupuncture. The beneficial effect of acupuncture on obesity is associated with increased plasma nesfatin-1 level.

Neuregulin-1 protects myocardial cells against H2 O2 -induced apoptosis by regulating endoplasmic reticulum stress.

Neuregulin-1 (NRG-1) is a stress-mediated growth factor secreted by cardiovascular endothelial cells and provides the protection to myocardial cells, but the underlying mechanisms are not fully understood. This study aimed to demonstrate that NRG-1 protects myocardial cells exposed to oxidative damage by regulating endoplasmic reticulum (ER) stress. Neonatal rat cardiac myocytes (NRCMs) were isolated and treated with H2 O2 as a cellular model of ER stress. NRCMs were pretreated with different concentrations of NRG-1. We found that NRG-1 increased the viability and reduced the apoptosis of NRCMs treated by H2 O2 . Moreover, NRG-1 reduced lactate dehydrogenase level, increased superoxide dismutase activity and decreased malondialdehyde content in NRCMs treated by H2 O2 . Finally, we demonstrated that NRG-1 alleviated ER stress and decreased CHOP and GRP78 protein levels in NRCMs treated by H2 O2 . Taken together, these data indicate that NRG-1 relieves oxidative and ER stress in NRCMs and suggest that NRG-1 is a promising agent for cardioprotection.

Neuregulin-1 suppresses cardiomyocyte apoptosis by activating PI3K/Akt and inhibiting mitochondrial permeability transition pore.

Neuregulin-1 (NRG-1) has been shown to attenuate cardiomyocyte apoptosis but the underlying signaling mechanism remains elusive. In this study, we focused on mitochondrial permeability transition pore (mPTP) opening and PI3K/Akt pathway to investigate the effects of NRG-1 on oxidative stress-induced apoptosis of cardiomyocyte. Human cardiac myocytes and neonatal rat cardiac myocytes were exposed to hydrogen peroxide with or without pre-treatment with recombinant human neuregulin-1 (rhNRG-1). Cell apoptosis and mPTP opening were assayed by flow cytometry and confocal microscopy. The activation of Akt was detected by western blot analysis. The results showed that H(2)O(2) induced cardiomyocyte apoptosis and activated mPTP. rhNRG-1 inhibited mPTP and activated Akt in the presence of H(2)O(2) and further protected the cells from H(2)O(2)-induced apoptosis. However, rhNRG-1 failed to inhibit mPTP opening and cell apoptosis in the presence of PI3K inhibitor LY294002. Taken together, these findings suggest that NRG-1 activates PI3K/Akt signaling and inhibits mPTP opening, and downstream apoptotic events in cardiac myocytes subjected to oxidative stress.

Neuregulin-1 attenuates mitochondrial dysfunction in a rat model of heart failure.

BACKGROUND: Mitochondrial dysfunction plays a pivotal role in the progression of left ventricular (LV) remodeling and heart failure (HF). Recombinant human neuregulin-1 (rhNRG-1) improves cardiac function in models of experimental HF and in clinical trials; however, its impact on mitochondrial function during chronic HF remains largely unknown. The purpose of this study was to investigate whether rhNRG-1 could attenuate the functional and structural changes that occur in cardiac mitochondria in a rat model of HF induced by myocardial infarction. METHODS: Sixty adult rats underwent sham or coronary ligation to induce HF. Four weeks after ligation, 29 animals with LV ejective fraction ≤ 50% were randomized to receive either vehicle or rhNRG-1 (10 µg×kg(-1)×d(-1), I.V.) for 10 days, another 12 sham-operated animals were given no treatment. Echocardiography was used to determine physiological changes. Mitochondrial membrane potential (MMP), respiratory function and tissue adenosine triphosphate (ATP) production were analyzed. Cytochrome c expression and cardiomyocyte apoptosis were determined. Oxidative stress was evaluated by reactive oxygen species production using fluorescence assays and gene expression of glutathione peroxidase measured by real-time quantitative PCR. RESULTS: Compared with sham-operated animals, vehicle treated HF rats exhibited severe LV remodeling and dysfunction, significant mitochondrial dysfunction, increased mitochondrial cytochrome c release, increased myocyte apoptosis and enhanced oxidative stress. Short-term treatment with rhNRG-1 significantly attenuated LV remodeling and cardiac function. Concomitant with this change, mitochondrial dysfunction was significantly attenuated; with ATP production, MMP and respiratory function restored, cytochrome c release and apoptosis inhibited, and oxidative stress reduced. CONCLUSION: The present study demonstrated that rhNRG-1 can significantly improve LV remodeling and cardiac function in the failing heart, this beneficial effect is related to reducing mitochondrial dysfunction, myocyte apoptosis and oxidative stress.

Factors influencing recovery of left ventricular structure in patients with chronic heart failure.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and ß-blockers (ßB) have beneficial effects on left ventricular (LV) remodeling, alleviate symptoms and reduce morbidity and mortality in patients with chronic heart failure (CHF). However the correlation between the d osages of ACE inhibitors, ßB, and recovery of LV structure remains controversial. Clinical factors associated with recovery of normal ventricular structure in CHF patients receiving medical therapy are poorly defined. Here we aimed to identify variables associated with recovery of normal or near-normal structure in patients with CHF. METHODS: We recruited 231 consecutive CHF outpatients, left ventricular ejection fraction (LVEF) ≤ 40% and left ventricular end diastolic diameter (LVEDD) > 55/50 mm (male/female), who were receiving optimal pharmacotherapy between January 2001 and June 2009, and followed them until December 31, 2009. They were divided into three groups according to LVEDD and whether they were still alive at final follow-up: group A, LVEDD ≤ 60/55 mm (male/female); group B, LVEDD > 60/55 mm (male/female); and group C, those who died before final follow-up. Apart from group C, univariate analysis was performed followed by Logistic multivariate analysis to determine the predictors of recovery of LV structure. RESULTS: A total of 217 patients completed follow-up, and median follow-up time was 35 months (range 6 - 108). Twenty-five patients died during that period; the all-cause mortality rate was 11.5%. Group A showed clinical characteristics as follows: the shortest duration of disease and shortest QRS width, the lowest N-terminal brain natriuretic peptide (NT-proBNP) at baseline, the highest dose of ßB usage, the highest systolic blood pressure (SBP), diastolic blood pressure (DBP) and the lowest New York Heart Association (NYHA) classification, serum creatinine, uric acid, total bilirubin and NT-proBNP after treatment. Logistic multivariate analysis was performed according to recovery or no recovery of LV structure. Data showed that LVEF at follow-up (P = 0.013), mitral regurgitation at baseline (P = 0.020), LVEDD at baseline (P = 0.031), and ßB dosage (P = 0.041) were independently associated with recovery of LV diameter. CONCLUSION: Our study suggests that four clinical variables may predict recovery of LV structure to normal or near-normal values with optimal drug therapy alone, and may be used to discriminate between patients who should receive optimal pharmacotherapy and those who require more aggressive therapeutic interventions.

[Optimal pharmacotherapy according to guideline improved prognosis of outpatients with chronic heart failure].

OBJECTIVE: To evaluate the effects of optimal pharmacotherapy according to guideline on treating chronic heart failure(CHF) in real world clinical practice. METHODS: A total of 231 consecutive outpatients with reduced left ventricular ejection fraction (LVEF ≤ 40%) and enlarged left ventricular end diastolic diameter (male > 55 mm, female > 60 mm) were recruited from January 2001 to June 2009. All patients were treated with optimal pharmacotherapy according to guideline recommendations and followed up to December 31, 2009. Mortality, rehospitalization and changes of heart size and cardiac function at baseline and at the end of follow-up period were analyzed. RESULTS: (1) 14 patients were lost during follow-up (6.1%), and follow-up was complete in 217 patients (93.9%). 97.2% and 98.2% patients were prescribed angiotensin converting enzyme (ACE) inhibitors and ß-blockers (ßB). Combined of ACE inhibitors and BB use was applied in 95.3% patients. The target dose of ACE inhibitors and ßB were reached in 50.7% and 37.3% patients. (2) Lower mortality and re-hospitalization rates were observed in this cohort: all-cause morality, average annual mortality was 11.5% and 3.9% respectively. Re-hospitalization rate was 27.6%. (3) Left ventricular end-diastolic diameter (LVEDD) decreased from (68.2 ± 7.2) mm to (62.2 ± 9.6) mm. LVEDD value was normal or near normal (male ≤ 60 mm, female ≤ 55 mm) in 43.2% patients. LVEF improved form (29.8 ± 7.5)% to (43.3 ± 11.8)%, LVEF was > 40% in 60.4% patients, LVEF was ≤ 40% but increased ≥ 10% after treatment in 22.9% patients. CONCLUSION: Optimal pharmacotherapy according to guideline can improve prognosis of outpatients with CHF.