Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy.

INTRODUCTION: Sepsis is a medical condition characterized by acute organ dysfunction and uncontrolled inflammation. Organ dysfunction in sepsis is the primary cause of mortality in patients with myocardial dysfunction. Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients. Our main objective is to examine levosimendan's efficacy in treating severe sepsis complicated with septic cardiomyopathy. METHODS: We systematically searched five databases, PubMed, Web of Science, Embase, Cochrane Library and BioMed Central, for articles and publications from their inception to 2023. Our study adopted the PICOS approach in identifying suitable publications during the systematic search. Inclusion criteria included randomized, controlled trials utilizing levosimendan in adult patients diagnosed with septic shock or severe sepsis. We excluded non-English publications and non-randomized controlled trials. The Newcastle-Ottawa scale (NOS) scale was used to assess the methodological quality, while the risk of bias was assessed through the Cochrane Risk of bias tool. All statistical analyses were performed using RevMan version 5.4. RESULTS: Eight studies met the eligibility criteria and were included in the analysis. There was a statistically significant positive effect on cardiac input in patients treated with levosimendan compared to those treated with dobutamine (p < 0.001). Similarly, there were positive effects on left ventricular ejection fraction (LVEF) (p < 0.001) and left ventricular stroke work index (LVSWI) (p < 0.001). We observed a significant reduction in mortality (p < 0.01) and serum levels of lactic acid (p < 0.01). DISCUSSION: Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues. CONCLUSION: Levosimendan is highly efficacious and safe in the management of sepsis and sepsis-induced cardiomyopathy.

Effects of laparoscopic splenectomy on surgical site wound infection in patients with spleen rupture: A meta-analysis.

A meta-analysis was performed to compare the effects of laparoscopic splenectomy (LS) and open splenectomy (OS) for splenic rupture on postoperative surgical site wound infections and postoperative complications. A comprehensive computerised search was conducted for studies comparing LS with OS for the treatment of splenic rupture in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases, with the search including studies published in any language between the creation of the databases and August 2023. Two researchers independently screened the literature and extracted the data. Literature quality was assessed using the Newcastle-Ottawa Scale, and the included data were collated and analysed using Stata 17.0 software for meta-analysis. Twenty-two studies involving 1545 patients were included. LS was superior to OS in the following aspects: reduced risk of postoperative surgical site wound infection (OR = 0.19, 95% CI: 0.11-0.34, p = 0.000), shortened hospital stay (standardised mean difference = -1.73, 95% CI: -2.05 to -1.40, p = 0.000), and reduced postoperative complication rate (OR = 0.22, 95% CI: 0.16-0.31, p = 0.000). Compared with OS, LS has a lower rate of postoperative wound infection, shorter hospital stay, and reduced rate of postoperative complications. LS is safe and effective for the treatment of splenic rupture and can be promoted clinically.

CADM1/TSLC1 inactivation by promoter hypermethylation is a frequent event in colorectal carcinogenesis and correlates with late stages of the disease.

Cell adhesion molecule 1 (CADM1/TSLC1), a putative tumor suppressor involving in cell adhesion, proliferation and apoptosis, is frequently inactivated in several carcinomas due to promoter hypermethylation. But alterations of CADM1/TSLC1 in colorectal carcinogenesis and clinical significance have not been elucidated yet. The aim of this study was to determine the role of functional inactivation of CADM1/TSLC1 gene in colorectal tumorigenesis and its potential as a novel epigenetic marker for clinical assessment of patients with colorectal cancer. We measured CADM1/TSLC1 expression levels in 8 colorectal cancer cell lines, 54 primary colorectal carcinomas and their corresponding non-cancerous tissues by reverse transcription polymerase chain reaction, western blot analysis and immunohistochemistry. We analyzed CADM1/TSLC1 promoter methylation status by bisulfite genomic sequencing and the methylation special polymerase chain reaction, and evaluated its correlation with clinicopathological characteristics. All statistical tests were 2-sides. Downregulation of CADM1/TSLC1 expression was observed in 7 of 8 (88%) colorectal cancer cell lines and in 39 of 54 (72%) primary colorectal carcinomas. Hypermethylation of CADM1/TSLC1 promoter region occurred in 6 of 8 (75%) colorectal cancer cell lines and 32 of 54 (59%) primary colorectal carcinomas, and was correlated with advanced colorectal carcinoma. Epigenetic inactivation of CADM1/TSLC1 gene is a frequent alteration in development of colorectal cancer and can be a potential biomarker for molecular staging of patients with colorectal cancer.

Artificial Intelligence-Assisted Colonoscopy for Detection of Colon Polyps: a Prospective, Randomized Cohort Study.

BACKGROUND AND AIMS: Improving the rate of polyp detection is an important measure to prevent colorectal cancer (CRC). Real-time automatic polyp detection systems, through deep learning methods, can learn and perform specific endoscopic tasks previously performed by endoscopists. The purpose of this study was to explore whether a high-performance, real-time automatic polyp detection system could improve the polyp detection rate (PDR) in the actual clinical environment. METHODS: The selected patients underwent same-day, back-to-back colonoscopies in a random order, with either traditional colonoscopy or artificial intelligence (AI)-assisted colonoscopy performed first by different experienced endoscopists (> 3000 colonoscopies). The primary outcome was the PDR. It was registered with clinicaltrials.gov . (NCT047126265). RESULTS: In this study, we randomized 150 patients. The AI system significantly increased the PDR (34.0% vs 38.7%, p < 0.001). In addition, AI-assisted colonoscopy increased the detection of polyps smaller than 6 mm (69 vs 91, p < 0.001), but no difference was found with regard to larger lesions. CONCLUSIONS: A real-time automatic polyp detection system can increase the PDR, primarily for diminutive polyps. However, a larger sample size is still needed in the follow-up study to further verify this conclusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT047126265.

Clinical outcome and left ventricular remodeling in AMI patients with insufficient myocardial reperfusion after recanalization.

AIM: Myocardial contrast echocardiography (MCE) is effective in predicting myocardial viability and functional recovery on a segmental level in patients with acute myocardial infarction (AMI). In this study, we investigated whether insufficient myocardial reperfusion plays an important role in left ventricular (LV) remodeling and functional recovery in patients with thrombolysis in myocardial infarction (TIMI) flow grade 3 and corrected TIMI frame count (CTFC) < 40 after recanalization of the infarct-related artery. METHOD: Patients underwent intracoronary injection of microbubbles for echocardiographic assessment of myocardial microvascular perfusion, wall motion score, LV volume and ejection function (EF) at baseline, 30 minutes, one month and six months after recanalization. The patients with MCESI < 1 were considered to have insufficient myocardial reperfusion (group A, n=11), while the patients with MCESI≥1 were considered to have sufficient myocardial reperfusion (group B, n=47) after AMI recanalization. RESULTS: The wall motion score index (WMSI) and the left ventricular ejection fraction (LVEF) showed significant improvement at 1 month and 6 months in group B, but only at six months in group A. Left ventricular end-systolic and end-diastolic volumes (LVESV and LVEDV) were also significantly decreased at one and six months in group B. WMSI, LVESV, LVEDV and LVEF were significantly improved in group B in comparison with group A at one month and six months (P < 0.01). By six months, significant correlations were seen in all patients between MCESI and changes in LVESV, LVEDV and LVEF at 6 months. Similar correlations were observed between the myocardial regional blood flow (Q) and changes in LVESV , LVEDV and LVEF. CONCLUSION: Insufficient myocardial reperfusion was a strong independent predictor of LV remodeling and functional recovery in AMI patients with TIMI flow grade 3 and CTFC < 40 after recanalization. MCE has important additional value for prognosis and risk assessment in patients with acute myocardial infarction following recanalization.

Value of myocardial regional perfusion on long-term function in collateral-dependent myocardium.

BACKGROUND: Collateral circulation is considered key for left ventricular (LV) function recovery in patients with chronic total occlusion (CTO). However, there are conflicting reports about the influence of collaterals on LV recovery after revascularization. METHODS: Echocardiographic assessment of regional myocardial perfusion, wall motion score (WMS), and left ventricular ejection fraction (LVEF) were performed in patients with angiographically visible collateral circulation of grades 2 and 3. RESULTS: The WMS and LVEF of group B (with presence of myocardial regional perfusion) were significantly improved at one month and six months compared to those of group A (with absence of myocardial regional perfusion). The correlation between myocardial regional blood flow and changes in WMS and LVEF was significant at 6 months in patients with angiographically visible collateral circulation of grade 2 and 3. Similar correlations were observed on myocardial contrast echocardiography (MCE) score index. CONCLUSION: Myocardial function recovery in patients with CTO is determined by myocardial regional perfusion. MCE has important value for prognosis and risk stratification in patients with CTO undergoing cardiac catheterization.

Delayed traumatic parasternal hernia causes jejunal necrosis: A case report.

Diaphragmatic injury is a common clinical condition, and it may be difficult to avoid diaphragmatic hernia if detection and treatment is not timely. Parasternal hernia is mostly congenital. It is relatively rare in adults, and intestinal obstruction as a complication of intrathoracic intestinal herniation occurs only rarely. We treated a patient in whom parasternal hernia occurred 2 years after thoracic injuries. We present the plain radiography and computed tomography findings of this adult patient with acute abdomen symptoms caused by parasternal hernia.

[Effect of proteasome inhibitor bortezomib on proliferation, apoptosis and SHIP gene expression in K562 cells].

This study was aimed to investigate the effects of proteasome inhibitor bortezomib on proliferation, apoptosis and the SHIP expression of K562 cells. K562 cells were treated with bortezomib of different concentrations. Cell proliferation was analyzed by MTT assay, cell apoptosis was detected by flow cytometry and SHIP mRNA expression was assayed by RT-PCR.The results showed that after being treated with 10, 20, 50 and 100 nmol/L bortezomib for 24 h, the inhibitory rates of K562 cells were (5.76 ± 1.47)%, (10.55 ± 1.59)%, (17.14 ± 2.05)% and (27.69 ± 3.57)% respectively, and were higher than that in control (1.30 ± 0.10); when K562 cells were treated with 20 nmol/L bortezomib for 24, 48 and 72 h, the inhibitory rates of cell proliferation were (10.55 ± 1.59)%, (16.33 ± 2.53)% and (19.78 ± 1.56)% respectively, there was statistic difference of cell proliferation rate between 24 h group and 48 h group (P < 0.05). After being treated with 10,20,50,100 nmol/L bortezomib for 24 h, the apoptotic rates of K562 cells were (12.7 ± 0.6)%, (26.9 ± 0.9)%, (32.6 ± 1.2)% and (72.5 ± 1.5)% respectively,and all higher than that in control (1.0 ± 0.5)% (P < 0.05). According to results of RT-PCR detection, the expression level of SHIP mRNA was obviously up-regulated after treatment with bortezomib, and showed statistical difference in comparison with control. It is concluded that bortezomib inhibits proliferation of K562 cells in time and concentration-dependent manner and induces apoptosis through up-regulation of SHIP gene.

Low molecular weight heparin relieves experimental colitis in mice by downregulating IL-1ß and inhibiting syndecan-1 shedding in the intestinal mucosa.

Low molecular weight heparin (LMWH) exhibits anti-inflammatory properties, but its effect on inflammation in colitis remains unclear. This study aimed to evaluate the therapeutic effects of LMWH on dextran sulfate sodium (DSS)-induced colitis in mice, in which acute colitis progresses to chronic colitis, and to explore the potential mechanism involved in this process. C57BL/6 mice were randomly divided into control, DSS, and DSS plus LMWH groups (n = 18). Disease activity was scored by a disease activity index (DAI). Histological changes were evaluated by hematoxylin and eosin (HE) staining. The mRNA levels of syndecan-1, interleukin (IL)-1ß, and IL-10 were determined by quantitative reverse transcription polymerase chain reaction. Protein expression of syndecan-1 was detected by immunohistochemistry. The serum syndecan-1 level was examined by a dot immunobinding assay. LMWH ameliorated the disease activity of colitis induced by DSS administration in mice. Colon destruction with the appearance of crypt damage, goblet cell loss, and a larger ulcer was found on day 12 after DSS administration, which was greatly relieved by the treatment of LMWH. LMWH upregulated syndecan-1 expression in the intestinal mucosa and reduced the serum syndecan-1 level on days 12 and 20 after DSS administration (P<0.05 vs. DSS group). In addition, LMWH significantly decreased the expression of both IL-1ß and IL-10 mRNA on days 12 and 20 (P<0.05 vs. DSS group). LMWH has therapeutic effects on colitis by downregulating inflammatory cytokines and inhibiting syndecan-1 shedding in the intestinal mucosa.

[Effect of tyrosine kinase inhibitor imatinib mesylate on K562 cell invasion by PTEN pathway].

AIM: To investigate the effect of tyrosine kinase inhibitor imatinib mesylate on the PTEN signaling pathway and the cell invasion in K562 cells. METHODS: K562 cells were treated with different concentrations of imatinib mesylate. After different time periods, the mRNA levels of BCR/ABL, PTEN and FAK were detected by real-time fluorescent quantitative PCR (FQ-PCR) to analyze their relationships. The protein level of FAK was detected by immunocytochemistry. The cell invasive ability was examined by Transwell (Boyden chamber) assay. RESULTS: In the initial 36 h, the expression level of PTEN mRNA was up-regulated and the FAK mRNA was down-regulated with the reduction of BCR/ABL fusion gene expression and the cell invasive ability of K562 cells was inhibited by 2 µg/mL imatinib mesylate. 48 h later, the PTEN mRNA expression level decreased and the FAK mRNA expression level was elevated with the restore of BCR/ABL fusion gene. BCR/ABL mRNA level presented a positive correlation with PTEN mRNA expression level, and a negative correlation with FAK mRNA. CONCLUSION: Tyrosine kinase inhibitor imatinib mesylate can regulate PTEN/FAK pathway and inhibit the leukemia K562 cell invasive ability via restraining BCR/ABL fusion gene.

[Efficacy of chitosan and hyaluronidase on skin damage caused by docetaxel extravasation in rats].

BACKGROUND & OBJECTIVE: Docetaxel extravasating into the surrounding tissues may lead to severe skin damage. No guideline for handling docetaxel extravasation has been proposed till now. This study was to explore the efficacy of chitosan and hyaluronidase on skin damage caused by docetaxel extravasation in a rat model. METHODS: A docetaxel extravasation model was established in both lower extremities of 30 Sprague-Dawley rats. The rats were divided into 6 groups and received chitosan embrocation, hyaluronidase injection, hyaluronidase injection plus chitosan embrocation, saline embrocation, or saline injection, or received no treatment as control. The occurrence rate and extent of skin damage, and the healing time were observed and compared. RESULTS: The occurrence rate of skin damage was significantly lower in hyaluronidase group and hyaluronidase plus chitosan group than in chitosan group, saline embrocation group, saline injection group, and control group (30% and 20% vs. 90%, 100%, 90% and 100%, P<0.05). The healing time was significantly shorter in hyaluronidase group and hyaluronidase plus chitosan group than in chitosan group, saline embrocation group, saline injection group, and control group [(12.00+/-3.00) days and (9.50+/-2.12) days vs. (18.33+/-2.00) days, (23.70+/-2.41) days, (18.44+/-2.01) days and (25.70+/-2.26) days, P<0.01], and was significantly shorter in chitosan group than in saline embrocation group and control group (P<0.01). CONCLUSIONS: Hyaluronidase alone or hyaluronidase plus chitosan could decrease the occurrence rate of skin damage caused by docetaxel extravasation in rats, and shorten the healing time. Chitosan embrocation can improve the damage healing, but cannot decrease the occurrence rate of skin damage.

[Avastin combined with cisplan inhibits malignant ascites production in nude mice bearing transplanted ovary carcinoma with high VEGF expression].

OBJECTIVE: To establish a nude mouse model of malignant ascites with human ovarian carcinoma cell line OVCAR3 which highly expresses VEGF and evaluate the therapeutic of Avastin combined with cisplan. METHODS: Forty-eight nude mice with malignant ascites resulting from intraperitoneal transplantation of human ovarian carcinoma cell line OVCAR3 were treated with intraperitoneal injection of Avastin, cisplan, their combination, and PBS, respectively, to observe the effect on ascites development, VEGF content in the ascites, peritoneal permeability, development of new vessels and number of tumor cells in the ascites. RESULTS: Avastin obviously inhibited ascites accumulation and peritoneal capillary permeability, reduced VEGF protein level and microvascular density in the tumor tissues and the number of red cells and tumor cells in the malignant ascites, and prolonged the survival of the mice. The combination of Avastin and cisplan further enhanced the therapeutic efficacy of Avastin. CONCLUSION: The bio-chemotherapeutic strategy with Avastin combined with cisplan can be a promising method for treatment of malignant ascites.