Search

Recent studies have revealed that the effect of intestinal microecological disorders on organismal physiology is not limited to the digestive system, which provides new perspectives for microecological studies and new ideas for clinical diagnosis and prevention of microecology-related diseases. Stress triggers impairment of intestinal mucosal barrier function, which could be duplicated by animal models. In this paper, pathological animal models with high prevalence and typical stressors-corresponding to three major stressors of external environmental factors, internal environmental factors, and social psychological factors, respectively exemplified by burns, intestinal ischemia-reperfusion injury (IIRI), and depression models-were selected. We summarized the construction and evaluation of these typical animal models and the effects of stress on the organism and intestinal barrier, as well as systematically discussed the effects of different stresses on the intestinal mucosal barrier and intestinal microecology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Lou, Gong, Bian, Liao, Wu, Jiao and Zhang.)

Objective: We investigate the characteristics of histological damage to myocardial cells in the ablation region and surrounding areas of the left ventricular epicardium in rabbits using our self-developed cardiac pulsed electric field (PEF) ablation instrument and ablation catheter., Methods: Forty eight New Zealand rabbits underwent ablation on the left ventricular myocardium after open-heart exposure with a cardiac arrhythmia PEF ablation device and ablation catheter developed by the Medical Translation Laboratory of Pulsed Electric Field Technology in Zhejiang Province. The ablation parameters were set as biphasic electrical pulses; voltage, ±800 V; pulse width, 10 μs; interphase delay, 500 us. Six rabbits were included in the sham group and 42 other rabbits were randomly divided into immediately, 6-h, 1-, 3-day, 1-, 2-, and 4-week post-ablation groups, with six rabbits in each group. Creatine kinase- (CK)-MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were measured before and at different time points after PEF ablation to analyze their dynamic evolution. Masson staining of tissue block sections of left ventricular myocardial ablation and adjacent tissue heart specimens was performed, and the occurrence of TUNEL apoptosis in myocardium tissue was analyzed., Results: All rabbits completed the PEF ablation procedure and the follow-up process. After PEF ablation, the levels of cardiac enzymes, including CK-MB, CK, and AST, increased significantly, peaking 1-3 days after the procedure. In particular, those of CK and CK-MB increased by 15-20 times but returned to the preoperative level after 2 weeks. Based on general observation, it was found that the myocardium in the ablation area was swollen immediately after PEF ablation. Masson staining analysis revealed that cardiomyocytes were broken and infiltrated by erythrocytes after 6 h. After 1 day, the cells started to experience atrophy and necrosis; after 3 days, fibrotic replacement of the necrotic area became obvious. Then, by 4 weeks, the myocardial cells were completely replaced by hyperplasia. Apoptosis occurred significantly at 6 h and peaked at 24 h post-ablation, demonstrating a 37.7-fold increase; apoptotic cell counts decreased significantly at 3 days post-ablation, and no significant apoptotic cardiomyocytes were seen after 1 week., Conclusion: After PEF ablation, cardiomyocytes showed apoptotic process and dyed, at least partially, through a secondary necrosis, the ablation boundary was clear, the ablation area was replaced by structurally intact fibroblasts, no island myocardium tissue were seen, and the ablation area vessels and nerves were not affected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Chen, Wu, Qiu, Hong, Chen and Zhang.)

Background: Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria., Methods: We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English., Results: By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01)., Conclusions: Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wen, Li, Wang, Chen, Tang, Zhou, Hong, Cheng, Wu, Zhang, Feng and Wang.)

Background: PD-1 blockade is highly effective in patients with mismatch repair-deficient or microsatellite instability-high metastatic colorectal cancer. The role of single-agent PD-1 blockade in the neoadjuvant setting for resectable mismatch repair-deficient or microsatellite instability-high colorectal cancer remains unclear. We investigated the efficacy and safety of PD-1 blockade with toripalimab, with or without the COX-2 inhibitor celecoxib, as neoadjuvant treatment for mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancers., Methods: The PD-1 Inhibitor in Microsatellite Instability Colorectal Cancer (PICC) trial was a single-centre, open-label, parallel-group, non-comparative, randomised, phase 2 study undertaken at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Eligible patients were aged 18-75 years, had histologically confirmed mismatch repair-deficient or microsatellite instability-high colorectal cancer, had clinical stage T3-T4 or any T with lymph node positivity (N+), Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1), without any stratification or balanced blocking, to receive toripalimab 3 mg/kg intravenously on day 1, with or without celecoxib 200 mg orally twice daily from day 1 to 14 of each 14-day cycle, for six cycles before surgical resection. Adjuvant treatment with toripalimab with or without celecoxib was permitted at the investigators' discretion. The primary endpoint was the proportion of patients with pathological complete response, defined as tumours without any viable tumour cells in the resected primary tumour sample and all sampled regional lymph nodes. All efficacy and safety analyses were assessed in the modified intention-to-treat population, which included all patients who were randomly assigned to treatment and who received at least one dose of toripalimab. This trial is registered with ClinicalTrials.gov, NCT03926338, and is ongoing., Findings: Between May 1, 2019, and April 1, 2021, 53 patients were screened, of whom 34 were randomly assigned to either the toripalimab plus celecoxib group (n=17) or the toripalimab monotherapy group (n=17). As of data cutoff (Aug 10, 2021), median follow-up was 14·9 months (IQR 8·8-17·0). All patients received study treatment and underwent surgical resection; there were no treatment-related surgical delays. All 34 patients had an R0 resection (>1 mm resection margin). 15 of 17 patients (88% [95% CI 64-99]) in the toripalimab plus celecoxib group and 11 of 17 patients (65% [38-86]) in the toripalimab monotherapy group had a pathological complete response. All patients continued to receive adjuvant toripalimab with or without celecoxib for a total perioperative duration of 6 months and were alive and free of recurrence at data cutoff. During neoadjuvant treatment, ten (59%) patients in the toripalimab plus celecoxib group and ten (59%) in the toripalimab monotherapy group had grade 1-2 treatment-related adverse events. Only one (3%) of 34 patients, who was in the toripalimab plus celecoxib group, had a grade 3 or higher treatment-related adverse event during the neoadjuvant phase, which was grade 3 increased aspartate aminotransferase levels. In the adjuvant phase, only one (3%) of 34 patients, who was in the toripalimab monotherapy group, had a grade 3 or higher treatment-related adverse events, which was grade 3 increased aspartate aminotransferase and alanine aminotransferase levels., Interpretation: Neoadjuvant toripalimab with or without celecoxib could be a potential therapeutic option for patients with mismatch repair deficient or microsatellite instability-high, locally advanced, colorectal cancer. This treatment was associated with a high pathological complete response rate and an acceptable safety profile, which did not compromise surgery. Longer term follow-up is needed to assess effects on survival-related endpoints., Funding: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To propose a method for the resection of the rectal anastomotic stenosis and anal reconstruction based on the transanal endoscopic technique through a transanal and transabdominal combined endoscopic resection, and to verify its clinical effectiveness., Methods: Thirty-eight patients with anastomotic stenosis were admitted to the Sixth Affiliated Hospital, Sun Yat-sen University, China, from January 2016 to September 2019. Patients were divided into an experimental group (17 patients) and a control group (21 patients) subjected to the removal of the intestinal stenosis followed by anal reconstruction, they underwent transanal and transabdominal endoscopic surgery and traditional transabdominal surgery, respectively. Data on intraoperative blood loss, operation time, postoperative recovery, and prognosis were collected., Results: (1) The median intraoperative blood loss was approximately 100 ml, without conversion to laparotomy during the surgery and intraoperative complications. The safety of the surgical operation was improved. (2) The operation time was shortened compared to previous reports, and the median operative time was 193 min. The average time of transanal endoscopic dissociation to the retroperitoneal fold was 76 min. (3) Laparoscopic assistance was carried out on 14 of the17 patients, and the incision was reduced. (4) The short-term curative effect was quite satisfactory, without permanent stoma. The average time to recover food intake after the surgery was 1.5 days. The average ambulation time was 3 days. Within 30 days after the surgery, one case suffered anastomotic leakage and then underwent refunctioning stoma through a second surgery. One patient suffered from intestinal obstruction, and the condition was improved through a conservative treatment. One case experienced delayed abdominal wound healing., Conclusion: The transanal and transabdominal endoscopic resection of the rectal anastomotic stenosis and anal reconstruction reduced the difficulty of the surgery, improved its safety, shortened the operation time, decreased the operative complications, and enabled patients to recover well after surgery., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The aim of this study was to analyze the computed tomography (CT), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), and clinical findings of pulmonary epithelioid hemangioendothelioma., Methods: Eighteen patients were included. We reviewed CT and PET/CT features and clinical information. Spearman correlation analysis was used to reveal the correlation between lesion size and maximum standardized uptake values (SUVmax)., Results: Eleven patients complained of different symptoms. The serum levels of tumor markers were elevated in 8 patients (44.4%). Multiple lesions were shown in 14 cases (77.8%). Eleven cases (61.1%) presented as bilateral multiple perivascular lesions. The size of the largest nodule was less than 20 mm in diameter in 11 cases (61.1%). Eleven cases underwent PET/CT examination, and 8 cases (72.7%) had increased FDG uptake. There was a positive correlation (Spearman correlation coefficient, 0.56; P = 0.009) between lesion size and SUVmax. Extrapulmonary involvement was shown in 7 cases, including the liver and bone., Conclusions: Pulmonary epithelioid hemangioendothelioma on CT scan usually showed multiple bilateral perivascular lung nodules, generally measuring less than 20 mm in diameter. Lesions usually showed increased FDG uptake on PET/CT scans. There was a positive correlation between lesion size and SUVmax. The liver and bone were the most frequently involved extrapulmonary organs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Coagulometer, known as blood coagulation analyzer, is a product that can provide accurate test results for medical diagnosis and treatment analysis by detecting a series of items closely related to thrombosis and hemostasis in coagulation reaction. On the basis of previous traditional methods, and with our deep understanding about the principles of hemagglutination detection, we propose a hemagglutination detection method by using the dual-magnetic circuit beads method. Then, the corresponding hemagglutination detection module is designed. The coagulation time of plasma can be measured by detecting the movement of the magnetic beads when the magnetic field intensity is appropriate. The activated partial thromboplastin time(APTT) of plasma is tested when the most suitable magnetic field intensity is found. The results preliminarily show that this blood coagulation test method is valid and the corresponding test module has a potential value in business.

We previously reported endo-β-1,3-glucanase ENG in combination with β-glucosidase BGL2 at low concentration induced stipe cell wall extension. This study further explored ENG could be replaced by endo-β-1,3(4)-glucanase ENG16A in combination with BGL2 to induce stipe cell wall extension; similarly, BGL2 could be replaced by β-glucosidase BGL1 to cooperate with ENG to induce stipe cell wall extension. However, ENG could not be replaced by exo-β-1,3-glucanase EXG in combination with BGL2 to induce stipe cell wall extension, although EXG alone released higher level of soluble sugars from the stipe cell walls during the reconstituted wall extension than that released from the stipe cell walls by a combination of ENG16A or ENG and BGL2 or BGL1, which was different from chitinase-mediated stipe cell wall extension. These results indicate endo-β-1,3-glucanases loosen the stipe cell wall, whereas exo-β-1,3-glucanases and β-glucosidases play a synergistic role to maintain a low and efficient concentration of endo-β-1,3-glucanases for stipe cell wall extension. Furthermore, ENG was expressed at a very high level in the matured pilei, in contrast, ENG16A was expressed at a very high level in the elongating apical stipe. Therefore, ENG16A might be involved in stipe elongation growth, while ENG might participate in autolysis of pilei., Competing Interests: Declaration of competing interest We declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Main Conclusion: The functional homologs WS1A and WS1B, identified by map-based cloning, control the burley character by affecting chloroplast development in tobacco, contributing to gene isolation and genetic improvement in polyploid crops. Burley represents a special type of tobacco (Nicotiana tabacum L.) cultivar that is characterized by a white stem with a high degree of chlorophyll deficiency. Although important progress in the research of burley tobacco has been made, the molecular mechanisms underlying this character remain unclear. Here, on the basis of our previous genetic analyses and preliminary mapping results, we isolated the White Stem 1A (WS1A) and WS1B genes using a map-based cloning approach. WS1A and WS1B are functional homologs with completely identical biological functions and highly similar expression patterns that control the burley character in tobacco. WS1A and WS1B are derived from Nicotiana sylvestris and Nicotiana tomentosiformis, the diploid ancestors of Nicotiana tabacum, respectively. The two genes encode zinc metalloproteases of the M50 family that are highly homologous to the Ethylene-dependent Gravitropism-deficient and Yellow-green 1 (EGY1) protein of Arabidopsis and the Lutescent 2 (L2) protein of tomato. Transmission electron microscopic examinations indicated that WS1A and WS1B are involved in the development of chloroplasts by controlling the formation of thylakoid membranes, very similar to that observed for EGY1 and L2. The genotyping of historical tobacco varieties revealed that a two-step mutation process occurred in WS1A and WS1B during the evolution of burley tobacco. We also discussed the strategy for gene map-based cloning in polyploid plants with complex genomes. This study will facilitate the identification of agronomically important genes in tobacco and other polyploid crops and provide insights into crop improvement via molecular approaches.

Background: Recent clinical studies have yielded controversial results regarding the effect of probiotics on lipid profiles. To assess the efficacy of probiotics in lowering serum lipid concentrations, we conducted a meta-analysis of randomized controlled trials (RCTs)., Methods: Literature from the PubMed, Embase and Cochrane databases were searched and screened. The effects of probiotics on lipid profiles were assessed by mean difference (MD) and 95% confidence interval (CI). All included studies were analyzed using Review Manager 5.3 (Cochrane Collaboration, 2014)., Results: A total of 19 RCTs, including 967 participants, met the inclusion criteria. Probiotic interventions reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to controls (placebo or no treatment) by -0.25mmol/L (95% CI: -0.39, -0.12) and -0.17mmol/L (95% CI: -0.25, -0.09), respectively. No significant effects of probiotics on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were found. The effects of probiotics on decreasing TC and LDL-C levels were greater for longer intervention times, certain probiotic strains, and in younger mildly hypercholesterolaemic subjects., Conclusion: This meta-analysis revealed that the use of probiotics can significantly lower TC and LDL-C levels in hypercholesterolaemic adults, which brings hope for reducing the risk factors for developing cardiovascular disease., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Objective: To compare two different routes of totally implantable venous access ports (TIVPs) from the upper arm vein and the subclavian vein in terms of complications for patients with gastrointestinal malignancy., Methods: Patients who underwent implantations of TIVPs from September 2013 to January 2015 were retrospectively evaluated. The outcome measurements were rates and types of postprocedural early-stage and long-term complications., Results: A total of 208 patients(upper arm vein group, 86; subclavian vein group, 122) were included in this study. All TIVPs were implanted successfully. The rate of catheter displacement was higher in upper arm vein group(14.0% vs 5.7%, P=0.04), while other postprocedural early-stage complications had no significant difference between the two groups. The occurrence of transfusion obstacle and rates of overall postprocedural long-term complications were significantly lower in upper arm vein group than that in subclavian vein group(1.2% vs. 9.8%, P=0.02; 7.0% vs. 27.0%, P=0.01, respectively)., Conclusion: Compared with subclavian vein group, upper arm vein group has lower postprocedural long-term complication rates and is recommended as a safe and comfortable choice for port implantation.

Objective: The three-dimensional (3D) structure of left atrial appendage (LAA) in atrial fibrillation patients were reconstructed by Mimics 3D imaging system, aiming at guiding for selection of both the size and location of the closure devices and making preliminary risk assessment of LAA closure with Watchman system., Methods: Inclusion criteria were: ten voluntary patients with both atrial fibrillation and indication for LAA closure aging from 40 to 85 years old with contraindication for oral anticoagulants or unwillingness to take long-term oral anticoagulation therapy from May to December 2014. 3D reconstruction of LAA was preoperatively made by Mimics 3D imaging system. With the Mimics 3D reconstruction model and the results of both transesophageal echocardiography (TEE) and LAA radiography, the size and location for the closure device were chosen. The devices were planted at the ostium of the LAA., Results: Ten atrial fibrillation patients were enrolled (average age: (66.3±11.9) years old) and all successfully implanted with the Watchman LAA closure devices. Nine of them were with non-valvular atrial fibrillation with average CHADS2-VAS score (3.2±1.7) and HAS-BLED score (2.7±1.6). The rest one was a valvular atrial fibrillation patient with the history of the percutaneous balloon mitral valvuloplasty (PBMV) without surgical indications of mitral valve replacement (MVR). There was no blood leakage around the device by regular postoperative TEE and LAA radiography examinations. There were no complications of bleeding, embolism, or stroke through both at peri-operative period and at 1 month follow-up post procedure., Conclusion: Preoperative Mimics 3D reconstruction of LAA by Mimics 3D imaging system among atrial fibrillation patients provides essential information guiding the successful LAA closures.