Extralobar pulmonary sequestration: A case report and literature review.

Pulmonary sequestration is a congenital malformation of lung development in which part of the lung tissue is separated from the normal lung during the embryonic phase and develops separately and receives blood supply from an aberrant systemic artery forming a nonrespiratory mass. In brief, early in embryonic development, certain tissues that should have atrophied and been gradually absorbed are left behind due to impairment of the atrophy process and form anomalous branches of the aorta, which pull parts of the lung tissue, isolating them from normal lung tissue and bronchi, and thus forming separate lung tissue. According to the relationship of the mass to the pleural covering, pulmonary sequestration can be divided into two types, intralobar pulmonary sequestration (ILS) and extralobar pulmonary sequestration (ELS), of which approximately 75% of cases are ILS, but ELS is less common. Symptoms are not obvious in either type, making diagnosis and differential diagnosis more difficult. Here we report a 33-year-old patient with only insignificant abdominal distension who was eventually diagnosed with retroperitoneal ELS.

SMC4, a novel tumor prognostic marker and potential tumor therapeutic target.

The structural maintenance of chromosome 4 (SMC4) is a member of the ATPase family of chromosomes. The most widely reported function of SMC4, as well as the remaining subunits of whole condensin complexes, is compression and dissociation of sister chromatids, DNA damage repair, DNA recombination, and pervasive transcription of the genome. Studies have also shown that SMC4 plays an exceedingly essential role in the division cycle of embryonic cells, such as RNA splicing, DNA metabolic process, cell adhesion, and extracellular matrix. On the other hand, SMC4 is also a positive regulator of the inflammatory innate immune response, while excessive innate immune responses not only disrupt immune homeostasis and may lead to autoimmune diseases, but even cancer. To further understand the expression and prognostic value of SMC4 in tumors, we provide an in-depth review of the literature and several bioinformatic databases, for example, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Human Protein Atlas and Kaplan Meier plotter tools, illustrating that SMC4 plays a vital role in the occurrence and development of tumors, and high expression of SMC4 seems to consistently predict worse overall survival. In conclusion, we present this review which introduces the structure, biological function of SMC4, and its correlation with the tumor in detail; it might provide new insight into a novel tumor prognostic marker and potential tumor therapeutic target.

Counterclockwise modular laparoscopic anatomical mesohepatectomy using combined glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches.

Background: Although laparoscopic anatomical hepatectomy (LAH) is widely adopted today, laparoscopic anatomic mesohepatectomy (LAMH) for patients with hepatocellular carcinoma (HCC) remains technically challenging. Methods: In this study, 6 patients suffering from solitary liver tumors located in the middle lobe of the liver underwent counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches. In this process, the Glissonean pedicle approach (Takasaki approach) was first used to transect the liver pedicles of segment right anterior (G58) and segment 4 (G4). Second, the hepatic vein-guided approach was performed along the umbilical fissure vein (UFV) to sever the liver parenchyma from the caudal to cranial direction, and the middle hepatic vein (MHV) and anterior fissure vein (AFV) were then disconnected at the root. Last, the hepatic vein-guided approach was once more performed along the ventral side of the right hepatic vein (RHV) to transect the liver parenchyma from the cranial to anterior direction, and the middle lobe of the liver, including the tumor, was removed completely. The entire process was applied in a counterclockwise fashion, and the exposure or transection sequence was G58, and G4, followed by UFV, MHV, AFV, and finally, the liver parenchyma along the ventral side of RHV. Results: The counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches was feasible in all 6 cases. The median duration of the operation was 275 ± 35.07 min, and the mean estimated blood loss was 283.33 ml. All of the 6 patients recovered smoothly. The Clavien-Dindo Grade I-II complications rate was up to 33.33%, mainly characterized by postoperative pain and a small amount of ascites. No Clavien-Dindo Grade III-V complications occurred, and the mean postoperative hospital stay was 6.83 ± 1.47 days. Follow-up results showed that the average disease-free survival (DFS) was 12.17 months, and the 21-months OS rate, DFS rate and tumor recurrent rate were 100%, 83.33% and 16.67% respectively. Conclusions: Counterclockwise modular LAMH using combined Glissonean pedicle (Takasaki approach) and hepatic vein-guided approaches takes the advantages of the two approaches, is a novel protocol for LAMH. It is thought to be technically feasible for patients with a centrally located solitary HCC. The oncologic feasibility of this technique needs to be investigated based on long-term follow-up. A multicenter, large-scale, more careful study is necessary.

microRNA-132 inhibits cardiomyocyte apoptosis and myocardial remodeling in myocardial infarction by targeting IL-1ß.

The patients suffering from myocardial infarction (MI) undergo cardiac remodeling with the features of expanded myocardial infarct size and dilated left ventricle. Multiple microRNAs (miRNAs) are emerged as crucial modulators to participate in the remodeling process. This study is mainly intended to clarify the regulatory mechanism of miR-132 in the MI-induced myocardial remodeling. miR-132 low expression, while interleukin-1ß (IL-1ß) high expression was determined in MI by reverse-transcription quantitative polymerase chain reaction and ELISA assays. MI rats showed decreased cardiac function and increased cardiomyocyte apoptosis. Moreover, miR-132 and IL-1ß levels were altered in cardiomyocytes to explore their role in MI, with levels of proapoptotic or antiapoptotic proteins in MI together with cardiac function indexes observed. In addition, upregulation of miR-132, decreased levels of Bax and Cleaved Caspase-3, increased left ventricular ejection fraction, left ventricular fractional shortening, the maximum rate of rise or decrease of left ventricular pressure (±dp/dtmax ), and Bcl-2 level, which could be reversed by overexpressing IL-1ß. All in all, miR-132 inhibits cardiomyocyte apoptosis so as to ameliorate myocardial remodeling in rats with MI through IL-1ß downregulation. Thus, miR-132 is a potential candidate for the MI treatment.

Comparative efficacy and safety of lipid-lowering agents in patients with hypercholesterolemia: A frequentist network meta-analysis.

BACKGROUND: The comparative efficacy and safety of PCSK9 inhibitors, statins, and ezetimibe to lower lipid levels in patients with hypercholesterolemia remain unknown. We aimed to investigate the benefits and harms of the lipid-lowering agents in these patients. METHODS: PubMed, Embase, and the Cochrane Library were searched from January 1, 2000 to June 1, 2018 for relevant randomized controlled trials (RCTs). Frequentist network meta-analysis was used to pool all estimates. Ranking probabilities were used to rank the comparative effects of all drugs against placebo. RESULTS: Eighty-four RCTs enrolled 246,706 patients were included. Most of the included were assessed as low risk of bias. The probabilities of PCSK9 inhibitors that ranked first in improving lipid outcomes were all 100%. The probability of statins that ranked first in reducing the risk of cardiovascular (CV) events was 60.6%, and the probability of PCSK9 inhibitor was 37.1%, while no significant difference of efficacy in reducing CV events was observed between the 2 agents (odds ratios [OR] 0.98, 95% CI 0.87-1.11). Statin ranked first in reducing all-cause and CV death. Compared with placebo, statins were associated with reduced risks of all-cause (OR 0.90, 95% CI 0.85-0.96) and CV death (OR 0.83, 95% CI 0.75-0.91) while PCSK9 inhibitors and ezetimibe were not. No agents caused adverse events (including neurocognitive events), except that statins therapy significantly increases the levels of alanine aminotransferase (ALT) (OR 1.89, 95% CI 1.42-2.51) and creatine kinase (CK) (OR 1.45, 95% CI 1.09-1.93) and the incidence of diabetes (OR 1.13, 95% CI 1.02-1.26). CONCLUSIONS: PCSK9 inhibitors were the most effective lipid-lowering agents in improving lipid levels. Furthermore, PCSK9 inhibitors achieved similar CV benefits like statins, while PCSK9 inhibitors were not associated with any increased risk of statin-related side-effects. Thus, PCSK9 inhibitors may also be recommended as promisingly first-line lipid-lowering treatment for patients with hypercholesterolemia, especially for these with statins intolerance or resistance.

Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion.

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.

Syringic acid inhibits apoptosis pathways via downregulation of p38MAPK and JNK signaling pathways in H9c2 cardiomyocytes following hypoxia/reoxygenation injury.

Syringic acid (SA), a naturally occur-ring O­methy-lated trihydroxybenzoic acid monomer extracted from Dendrobium nobile Lindl., has been demonstrated to attenuate renal ischemia­reperfusion (I/R) injury. However, the role of SA in myocardial I/R injury is unclear. The present study aimed to clarify the cardioprotective effect of SA in myocardial I/R injury in vitro and explore the potential molecular mechanisms. In the present study, it was revealed that pretreatment with SA increased the viability and inhibited oxidant stress in H9c2 cardiomyocytes that had suffered hypoxia/reoxygenation (H/R). SA also markedly downregulated B­cell lymphoma 2 (Bcl­2) expression and inhibited the expression of Bcl­2­like protein 4 (Bax) and cleaved caspase­3 in H9c2 cardiomyocytes induced by H/R. In addition, SA significantly alleviated H/R-induced the phosphorylation of p38 mitogen­activated protein kinase (p38MAPK) and c­Jun N­terminal kinase (JNK) in H9c2 cardiomyocytes. In conclusion, the present study demonstrated that SA inhibits the apoptosis of H9c2 cardiomyocytes following H/R injury via reduced activation of the p38MAPK and JNK signaling pathways. The results support the therapeutic usage of SA in the treatment of myocardial infarction.

Effect of cardiac resynchronization therapy on patients with heart failure and narrow QRS complexes: a meta-analysis of five randomized controlled trials.

PURPOSE: Although cardiac resynchronization therapy (CRT) has been demonstrated extensively to benefit heart failure (HF) patients with wide QRS complexes, the effect of CRT in patients with narrow QRS complexes remains unclear. This meta-analysis aimed to determine whether HF patients with narrow QRS complexes may benefit from CRT. METHODS: A search of MEDLINE, EMBASE, and Cochrane databases was performed to identify randomized controlled trials (RCTs) that investigated the effect of CRT in HF patients with narrow QRS complexes (< 130 ms). Outcomes included all-cause mortality, heart failure-related death or hospitalization, 6-min walk distance, quality of life ejection fraction, end-systolic volume, and end-diastolic volume. RESULTS: A total of five RCTs involving 1246 HF patients with narrow QRS complexes were included. The frequency of all-cause mortality for patients receiving CRT versus the control group was 10 versus 7 % (relative risk [RR] 1.45, 95 % confidence interval [CI] 1.002 to 2.091, P = 0.049). CRT did not reduce heart failure-related mortality (RR 0.89; 95 % CI 0.52 to 1.54; P = 0.69) or hospitalization (RR 0.99, 95 % CI 0.79 to 1.23, P = 0.91). In addition, CRT did not improve average 6-min walk distance (weighted mean difference [WMD] 39.28 m, 95 % CI -71.04 to 149.61 m, P = 0.49), QOL scores (WMD 0.64 points, 95 % CI -2.15.10 to 3.43 points, P = 0.65), or ejection fraction (WMD 0.90 %, 95 % CI -0.71 to 2.51 %, P = 0.28). CONCLUSIONS: In HF patients with reduced left ventricular ejection fraction (≤ 35 %) and narrow QRS complexes (< 130 ms), CRT did not improve clinical or functional outcomes and may actually increase all-cause mortality.

Selective depletion of tumor neovasculature by microbubble destruction with appropriate ultrasound pressure.

Low-intensity ultrasound-microbubble (LIUS-MB) treatment is a promising antivascular therapy for tumors. We sought to determine whether LIUS-MB treatment with an appropriate ultrasound pressure could achieve substantial and persistent cessation of tumor perfusion without having significant effects on normal tissue. Further, we investigated the mechanisms underlying this treatment. Murine S-180 sarcomas, thigh muscles, and skin tissue from 60 tumor-bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Subsequently, contrast-enhanced ultrasonic imaging and histological studies were performed. Tumor microvessels, tumor cell necrosis, apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment with the selected ultrasound pressure. We found that twenty-four hours after LIUS-MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had substantially decreased by 84 ± 8% and 84%, respectively (p < 0.01). Similar reductions were not observed in the muscle or skin. Additionally, an extreme reduction in the number of immature vessels was observed in the tumor (reduced by 90%, p < 0.01), while the decrease in mature vessels was not significant. Further, LIUS-MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis, delayed tumor growth, and increased the survival rate of tumor-bearing mice (p < 0.01). These findings indicate that LIUS-MB treatment with an appropriate ultrasound pressure could selectively and persistently reduce tumor perfusion by depleting the neovasculature. Therefore, LIUS-MB treatment offers great promise for clinical applications in antivascular therapy for solid tumors.

Histamine H2 receptor activation exacerbates myocardial ischemia/reperfusion injury by disturbing mitochondrial and endothelial function.

There is evidence that H2R blockade improves ischemia/reperfusion (I/R) injury, but the underlying cellular mechanisms remain unclear. Histamine is known to increase vascular permeability and induce apoptosis, and these effects are closely associated with endothelial and mitochondrial dysfunction, respectively. Here, we investigated whether activation of the histamine H2 receptor (H2R) exacerbates myocardial I/R injury by increasing mitochondrial and endothelial permeability. Serum histamine levels were measured in patients with coronary heart disease, while the influence of H2R activation was assessed on mitochondrial and endothelial function in cultured cardiomyocytes or vascular endothelial cells, and myocardial I/R injury in mice. The serum histamine level was more than twofold higher in patients with acute myocardial infarction than in patients with angina or healthy controls. In neonatal rat cardiomyocytes, histamine dose-dependently reduced viability and induced apoptosis. Mitochondrial permeability and the levels of p-ERK1/2, Bax, p-DAPK2, and caspase 3 were increased by H2R agonists. In cultured human umbilical vein endothelial cells (HUVECs), H2R activation increased p-ERK1/2 and p-moesin levels and also enhanced permeability of HUVEC monolayer. All of these effects were abolished by the H2R blocker famotidine or the ERK inhibitor U0126. After I/R injury or permanent ischemia, the infarct size was reduced by famotidine and increased by an H2R agonist in wild-type mice. In H2R KO mice, the infarct size was smaller; myocardial p-ERK1/2, p-DAPK2, and mitochondrial Bax were downregulated. These findings indicate that H2R activation exaggerates myocardial I/R injury by promoting myocardial mitochondrial dysfunction and by increasing cardiac vascular endothelial permeability.