The value of single-channel endoscopic traction and kiss suture technique in closing wounds caused by endoscopic resection of gastrointestinal muscularis propria tumors.

BACKGROUND: To investigate the value of single forceps endoscopic traction stapling suture technique (SFETSST) in closing wounds caused by endoscopic resection of gastrointestinal muscularis propria tumor (GMPT). METHODS: Consecutive patients who underwent submucosal tumor excavation (ESE) and endoscopic full-thickness resection (EFR) for GMPT in the Second Affiliated Hospital of Xiamen Medical College from January 2015 to January 2022 were retrospectively collected. They were divided into the SFETSST group and the standard group (patients who receive single forceps traction-free endoscopic suture technique). The healing effects were compared between the two groups. RESULTS: Seventy-seven patients were included in our study with 50 patients included in SFETSST group. The baseline characteristics had no significant difference between the two groups. The technical success rate of wound suture in SFETSST cluster was significantly upper than that within standard cluster (100% vs. 88.89%, P = 0.04). The wound suture time in SFETSST cluster was significantly lower than that within standard cluster (33.19 ± 10.64 min, P < 0.001). Moreover, the incidence rates of intra-operative and postoperative complications in SFETSST cluster were lower than standard cluster (0 vs. 7.41%, P = 0.051 and 0 vs. 11.11%, P = 0.016). Interestingly, the SFETSST cluster had lower cost of consumables (2485.40 ± 591.78 vs. 4098.52 ± 1903.06 Yuan, P = 0.01) and shorter hospital stay (4.96 ± 0.90 vs. 7.19 ± 2.45, P < 0.001) than standard cluster. CONCLUSION: Our study showed that to fully closure the full-thickness defects of digestive tract, SFETSST was effective, safe, and economical, which was worth popularizing.

Resveratrol Attenuates Sepsis-Induced Cardiomyopathy in Rats through Anti-Ferroptosis via the Sirt1/Nrf2 Pathway.

Background: Sepsis-induced cardiomyopathy (SIC) is a severe myocardial dysfunction secondary to septicemia. It is a major concern owing to the high mortality and morbidity, which are greatly influenced by ferroptosis. Resveratrol (RSV) is a naturally existing agonist of the silent information regulator 1 (Sirt1). It has cardioprotective effects against sepsis-induced myocardial injury, However, the detailed mechanism is unknown.Methods: In this study, cecal ligation and puncture (CLP)-induced septic rats were employed to assess the changes in ferroptosis with RSV administration. According to the different treatments the rats were divided into the following groups: (1) the Sham, (2) CLP, (3) CLP + RSV at various doses (10, 30, and 50 mg/kg), and (4) CLP + Fer-1(a ferroptotic inhibitor) groups. After 24 h, the structure and function of the cardiac system in rats were evaluated, and mitochondrial morphology, ferroptosis-related biomarkers, and the levels of Sirt1/Nrf2 were assessed.Results: The rats that underwent CLP had suffered cardiac dysfunction, accompanied with myocardial damage, impaired mitochondria, elevated lipid peroxidation, and reduced Sirt1/Nrf2 expression in the myocardium. High-dose RSV successfully improved heart function, reversing the abnormalities in a dose-dependent manner. We then used EX527, a selective Sirt1 inhibitor, to further identify the intermediate signaling targets of RSV that regulate ferroptosis. EX527 diminished the curative effects of high-doses RSV.Conclusions: Summarily, our findings suggest a novel mechanism of RSV in reducing SIC: ferroptosis inhibition via upregulation of Sirt1/Nrf2 signaling pathways. This may be an effective therapeutic approach against organ failure in sepsis, particularly SIC.

[Hydrogen Sulfide Ameliorates Myocardial Injury Caused by Sepsis Through Suppressing ROS-Mediated Endoplasmic Reticulum Stress].

Objective: To investigate the effect of hydrogen sulfide (H 2S) on reactive oxygen species (ROS)-mediated endoplasmic reticulum stress in myocardial injury caused by sepsis. Methods: A sepsis model was induced in Sprague-Dawley (SD) rats by cecal ligation and puncture (CLP). The rats were randomly divided into sham operation (sham) group, sepsis (CLP) group, and sepsis+sodium hydrosulfide (NaHS) (CLP+NaHS) group. The left ventricular function of the rats was observed with echocardiography and their plasma H 2S levels were measured. Lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH) levels were measured and HE staining was done to evaluate the level of myocardial oxidative stress in rats. HE staining was done to observe the morphological changes of rat myocardium, and transmission electron microscope was used to observe the ultrastructure of myocardial mitochondria. Western blot was done to examine changes in the expression of two endogenous hydrogen sulfide synthases, cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MST), and changes in the expression of endoplasmic reticulum stress (ERS) marker proteins, including phosphorylated (p) protein kinase R-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic translation initiation factor 2α (p-eIF2α), p-inositol requires enzyme 1α (IRE1α), recombinant activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). TUNEL staining was performed to observe the changes of cardiomyocyte apoptosis in rats. Results: Left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS) and plasma H 2S decreased in septic rats ( P<0.05). Plasma H 2S exhibited linear correlation with LVEF and LVFS ( r 2=0.62 and r 2=0.64, all P<0.05). The ROS levels were significantly elevated in rats of the CLP group. In addition, these rats showed increased level of LDH ( P<0.05), increased expression of MDA ( P<0.05), and decreased expression of GSH ( P<0.05). Inflammatory cell infiltration and cardiomyocyte edema were observed in HE staining. Transmission electron microscopic observation revealed significant mitochondrial damage, observable mitochondrial edema, and cristae structure dissolution. The Western blot results showed that the expression levels of CSE and 3-MST decreased ( P<0.05), while the ERS marker proteins, including p-PERK, p-eIF2, IRE1α, ATF4, and CHOP, were expressed at increased levels ( P<0.05). TUNEL staining showed significant increase of apoptosis in cardiomyocytes ( P<0.05). After NaHS treatment, LVEF and LVFS increased ( P<0.05) and plasma H 2S increased in septic rats ( P<0.05). Myocardial oxidative stress levels decreased. HE staining and transmission electron microscopy showed improved myocardial morphology. Mitochondrial damage was reduced and CSE and 3-MST levels were significantly increased ( P<0.05). The expression of p-PERK, p-eIF2α, p-IRE1α, and CHOP proteins decreased ( P<0.05). A decrease in cardiomyocyte apoptosis levels was observed by TUNEL staining ( P<0.05). Conclusion: H 2S reduces septic cardiomyocyte apoptosis by inhibiting ROS-mediated ERS, thereby improving myocardial dysfunction in sepsis.

Efficacy and safety of moxibustion in the treatment of cancer-related fatigue: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer-related fatigue, a common symptom of cancer patients caused by the interaction of multiple factors, runs through the whole process of tumorigenesis, development, treatment, and prognosis. The main clinical manifestations are weakness, tiredness, exhaustion, fatigue, or slow movement, heavy limbs, low mood or irritability, sleep disturbance or lethargy, lack of attention, etc. CRF is different from the fatigue after daily body fatigue. It has no obvious relief or relief after rest or sleep, and exists for a long time in the relevant treatment and rehabilitation process. It seriously affects the physiological, psychological and social functions of patients, and reduces the quality of life of patients. Moxibustion therapy has shown strong advantages in the treatment of CRF, and the curative effect is accurate. Therefore, this paper will carry out a systematic evaluation and meta analysis of the efficacy and safety of moxibustion in the treatment of CRF. METHODS: we will searching 8 electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang Database, and Chinese Biomedical Literature Database. We will search above electronic databases from the beginning to January 2021, without any language restriction. Clinical efficacy, including total effective rate or cure rate, clinical symptom integral, and recurrence rate will be accepted as the primary outcomes. The fatigue scale score, quality of life improvement rate will be used as secondary outcomes. RevMan 5.3 software will be used for statistical analysis. The result about the curative effect and safety of moxibustion for cancer-related fatigue will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: When this research program is completed, the relevant results can be obtained. CONCLUSIONS: The results of this study will provide reliable evidence for the efficacy and safety of moxibustion in the treatment of cancer-related fatigue. ETHICS AND DISSEMINATION: This article does not need to pass the ethics committee review, because this article does not involve the ethics question, only collates the related literature research. INPLASY REGISTRATION NUMBER: INPLASY202110072.

H2S attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism.

The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H2S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H2S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H2S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H2S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H2S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H2S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H2S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H2S. Additionally, H2S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H2S. In conclusion, the results of the current study suggest that exogenous H2S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.

Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats.

Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than in the CLP + NaHS group (P<0.05). In conclusion, H2S acted as an anti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H2S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H2S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H2S.

Endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced liver injury.

Endoplasmic reticulum (ER) stress has been increasingly recognized to have an important role in various liver diseases. Sepsis-induced multi-organ failure remains to have a high mortality rate, and the liver plays a central pathophysiological role. This study aims to explore whether ER stress is involved in liver injury in septic rats. Sepsis was induced via cecal ligation and puncture (CLP). Rats were randomly divided into five groups as follows: sham, CLP 2 h, CLP 6 h, CLP 12 h, and CLP 24 h. They were monitored to record body weight (BW) and liver weight changes for every time point after surgery. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected via colorimetric activity assays. In addition, the morphological changes of the liver tissue were evaluated by staining the sections with hematoxylin and eosin and observing under light microscopy. The levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and cleaved caspase-12 were detected via Western blot analysis. Apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. The results showed that septic rat serums ALT and AST were increased, with the increase being more obvious in the CLP 24 h group. In addition, septic rats appeared to have histopathological abnormalities in the liver. The liver weight and index increased after CLP. No differences were noted in the BW between septic groups. The level of GRP78, CHOP, and cleaved caspase-12 were upregulated after CLP. However, CHOP and caspase-12 were induced later than GRP78. The density of TUNEL-positive apoptotic hepatocytes was significantly increased after 12 h and 24 h CLP. It indicates that the unfolded protein response occurred in the early stage of sepsis-induced liver damage. The ER stress-mediated apoptosis signal pathway is among the mechanisms of septic liver injury and may be a target in clinical prevention and therapy of sepsis-induced liver injury.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.

Effects of combined thymosin and hydrocortisone on immune response in septic mice.

This study is to investigate the effects of the thymosin α1 (Tα1) and hydrocortisone (HC) combination treatment on the immune responses in septic mice. According to different treatments, mice were divided into the control group (n = 18), the sepsis model group (n = 18), the Tα1 group (n = 18), the HC group (n = 18), and the Tα1+HC group (n = 18). Septic mouse model was established by the intraperitoneal injection of lipopolysaccharide (LPS). At 72 h after modeling, flow cytometry was used to analyze the dendritic cell (DC) numbers in peripheral blood and the expressions of MHC II and CD86. Tumor necrosis factor-α (TNF-α) level was measured by ELISA. Treatments of Tα1 and/or HC dramatically increased the survival rates of LPS-induced septic mice. Flow cytometry showed that, the DC numbers in peripheral blood were significantly decreased in the sepsis model group, which could be dramatically elevated by Tα1 treatment alone and in combination with HC (Tα1+HC). However, the DCs were undetectable in the HC group. In addition, the MHC II expression level was decreased in the sepsis model group, which was further declined in the Tα1 and Tα1+HC groups. The expression level of CD86 was elevated in the model group, which could be significantly down-regulated by the treatments of Tα1 and Tα1+HC. ELISA showed that, the peripheral blood TNF-α level in the HC group was lower than in the sepsis model group. Compared with the sepsis model group, the TNF-α levels were significantly elevated in the Tα1 and Tα1+HC groups. Tα1 and HC combination treatment could improve the immune function and regulate the inflammatory response to increase the survival rates of LPS-induced septic mice.

Effects of different types of fluid resuscitation on hepatic mitochondria and apoptosis.

The aim of this study was to observe the effects of different types of fluid resuscitation on hepatic mitochondria and apoptosis in hemorrhagic shock, and the corresponding mechanisms. Forty rats were divided into five groups: Sham surgery (Sham group), shock (Shock group), Ringer's lactate resuscitation (RL group), hydroxyethyl starch resuscitation (HES group) and autologous blood resuscitation (BL group). A model of hemorrhagic shock was successfully induced in the latter four groups. The recovery objective was to maintain the mean arterial pressure (MAP) of the rats at 80 mmHg. Two hours after the end of the recovery experiment, fresh liver samples were examined in order to observe the changes in the morphology and mitochondrial membrane potential (ΔΨm). In addition, the levels of succinate dehydrogenase (SDH) activity were assessed, and a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was conducted to evaluate the level of apoptosis in the liver cells. In the Shock, RL, HES and BL groups, mitochondrial ultrastructural damage in the liver cells, significant reductions in liver cell function, liver ΔΨm and SDH activity, and the apoptosis of hepatocytes were more apparent compared with those in the Sham group. In the BL group, compared with the RL and HES groups, the injuries to the mitochondrial ultrastructure and liver cell function were significantly reduced, the hepatic ΔΨm and SDH activity were significantly increased and the hepatocyte apoptosis index (AI) was significantly reduced (P<0.05). In conclusion, in a rat model of hemorrhagic shock, different methods of fluid resuscitation may improve the liver cells with regard to mitochondrial ultrastructure and function, the stability of liver ΔΨm, the activity of SDH and the inhibition of liver cell apoptosis. The results indicate that infusion with autologous blood followed by RL solution is a preferable method of fluid resuscitation compared with HES.

The protective effects and potential mechanism of Calpain inhibitor Calpeptin against focal cerebral ischemia-reperfusion injury in rats.

To demonstrate the protective effects of Calpeptin as the Calpain inhibitor against focal cerebral ischemia-reperfusion injury in rats and to explore it's possible mechanism. 96 rats were randomly divided into four groups. The model of middle cerebral artery occlusion was used for the research of focal cerebral ischemia. Using this animal model, the effects of Calpeptin on the neurological functions, infarction volume and infarction volume percentage of brain, Caspase-3 expression and neuronal apoptosis in hippocampal CA1 sector after focal cerebral ischemia-reperfusion injury in rats were investigated. The current results confirmed that Calpeptin as the Calpain inhibitor might paly an important role for neuroprotection against focal cerebral ischemia-reperfusion injury. Calpeptin could reduce the neuronal apoptosis in hippocampal CA1 sector when the rats was subjected to the focal cerebral ischemia-reperfusion, the potential mechanism might be related to the inhibition of the expression of Caspase-3 by Calpeptin. However, it is still unknown to what the exact mechanism of Calpeptin inhibits the activation of Caspase-3 in this process. Therefore, further research needs to be done to unravel the underlying mechanisms in the future.

Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population.

BACKGROUND: It has been proposed that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) could affect the expression of the miRNA and contribute to the susceptibility of human tumors. However, the role of genetic variant (T/C) in miR-196a-2 in gastric cancer susceptibility is still unknown. OBJECTIVES: To evaluate the association between genetic polymorphism of miR-196a-2 (rs11614913) and risk of gastric cancer, a hospital-based case-control study was conducted in a Chinese population. METHODS: The miR-196a-2 polymorphism was determined using the method of polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 213 gastric cancer patients and 213 age- and sex-matched controls. RESULTS: In the present study, we found that a significantly increased risk of gastric cancer in subjects with the variant homozygote CC of miR-196a-2 compared with wild-type homozygote TT and heterozygote CT carriers (adjusted odds ratio (OR) = 1.57, 95% confidence interval (CI) = 1.03-2.39, P = 0.038). Stratified analyses indicated that the variant homozygote CC genotype had a strong association with lymph node metastasis of gastric cancer (adjusted OR = 2.25, 95% CI = 1.21-4.18, P = 0.011). CONCLUSIONS: These findings suggest that the genetic variant within miR-196a-2 could play an important role in the development and progression of gastric cancer. We expect the findings may be helpful to better understand the mechanism of gastric carcinogenesis.