Expression of G3BP and RhoC in esophageal squamous carcinoma and their effect on prognosis

AIM: To investigate the expression and significance of G3BP and RhoC proteins in esophageal squamous carcinoma (ESC). METHODS: The expression of G3BP and Rhoc proteins in 80 cases of ESC was detected by immunohistochemistry. The relationship was studied between the expression of the two proteins and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC. RESULTS: The positive expression rate of G3BP in ESC was 71.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non- lymph node metastasis group (Z = -2.283, P = 0.022), but no relations were found between G3BP expression and tumor size, differentiation degree and TNM stage (P > 0.05). The group with G3BP positive expression had shorter survival time than the group with G3BP negative expression (P = 0.000). The positive expression rate of RhoC in ESC was 66.25%; and the rate in the lymph node metastasis group was significantly higher than that in the non-lymph node metastasis group (Z = -2.115, P < 0.05), but no relations were found between RhoC expression and tumor size, differentiation degree and TNM stage (P > 0.05). The RhoC positive expression group had a shorter survival time than the RhoC negative expression group (P < 0.001. The expression of G3BP protein correlated positively with the expression of RhoC in ESC tissues (rs = 0.656, P < 0.001). CONCLUSION: The expression of G3BP and RhoC protein is closely related to the lymph node metastasis and survival in ESC patients. G3BP and RhoC proteins can be considered as predictors of prognosis in ESC patients.

The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/ epithelial mesenchymal transition pathway

Objective:Sorafenib resistance has been a major factor limiting its clinical use as a targeted drug in liver cancer.The present study aimed to investigate whether cryptotanshinone can enhance the sensitivity of liver cancer and reduce the resistance to sorafenib.Methods:Sorafenib-resistant cells were established based on HepG2 and Huh7 cell lines.And the anti-tumor effect of sorafenib combined with cryptotanshinone on the sorafenib-resistant cells was verified by MTT,colony formation,transwell assays and tumor growth xenograft model.Moreover,the effects of the combined treatment on the expression of phosphorylated(p)-STAT3,as well as epithelial mesenchymal transition(EMT)and apoptosis related proteins of cells were evaluated by western blot analysis.Results:It was identified that cryptotanshinone inhibited the viability of both HepG2 and Huh7 cells in a dose-and time-dependent manner,and decreased p-STAT3 expression rather than total STAT3 expression at a concentration of 40μmol/L.In the sorafenib-resistant cells,sorafenib in combination with cryptotanshinone markedly inhibited cell viability,invasion and migration compared with sorafenib alone.In contrast,increased p-STAT3 level by colivelin led to the inhibition of the synergistic effect of cryptotanshinone and sorafenib not only on cell viability,but also on EMT and apoptosis,suggesting that cryptotanshinone and sorafenib may act by downregulating STAT3 signaling.Further,the inhibition of carcinogenicity effect was also verified in xenografted tumor models.Conclusion:The present results indicated that cryptotanshinone could synergize with sorafenib to inhibit the proliferative,invasive,and migratory abilities of sorafenib-resistant cells by downregulating STAT3 signaling.

The Evaluation Characteristics of Type B Aortic Intramural Hematoma and Ten Years Treatment Outcomes

Background: Type B aortic intramural hematoma (IMH-B) is recognized as a subset of aortic dissection. The evolution of uncomplicated IMH-B is very difficult to predict. How and when to deal with this disease is unclear. The present study constructed two models to explore this problem. One is the morphology evolution model, which explored the risk factors and predictors for the IMH-B patients. Another is the predictive model confirmed the predictors and the time for invasive treatment of uncomplicated IMH-B patients. Objective: To explore the evolution predictors and detect the time for invasive treatment of uncomplicated IMH-B patients. Methods: Themorphology evolution model demonstrated that all 81 patients were diagnosis with CTA images. The initial and follow-up data were retrospectively studied. The evolution data were collection and measurement from initial and follow-up CTA images data. The predictive model showed that predictors of progression were detected with cox regression analysis. Results: All 81IMH-B patients were followed-up ranged from 1.2 to 36 months (median, 22 months). 26 patients accepted invasive treatment (24 underwent TEVAR and 2 underwent Surgery). 55 patients received medical treatment. Invasive treatment (IT) group overall events are 1/26 (3.8%); medical treatment (MT) group overall events are 33/55 (60.0%); IT group vs. MT group: p < 0.001. Moreover, we found that most events related aorta occurred within 30 days. Multivariate Cox regression analysis MDAD (hazard ratio, 3.58;95% CI, 1.25- 5.78;p < 0.001), MDAHT (hazard ratio, 4.26;95% CI, 0.85 - 7.84;p < 0.001), and IMH with PAU (hazard ratio, 3.58;95% CI, 1.02 - 5.63;p < 0.001) were confirmed as the independent predictors. Conclusions: MDAD > 45 mm, MDAHT > 10 mm, and IMH with PAU may be the important predictors for uncomplicated IMH-B patients. Most adverse aorta related events occurred within 30 days. It would be careful follow-up, closely observe for these patients within 30 days, and take necessary treatment strategies in time.

Experim ental Study of China-madeJiu Ling Solid Pyrolytic Carbon BileafletProsthetic Heart Valve In Sheep

To assess the hemodynamic performance and biocompatibility of China-made solid pyrolytic carbon bileaflet valve prosthesis so as to provide evidences for clinical trial,fifteen sheep aged 5-6 months underwent mitral replacement with 21-mm JiuLing valve under cardiopulmonary bypass. The first ten sheep underwent preliminary study to establish the trial methods and the matching of animal weight and prosthesis size, other five underwent formal experiment. The hemodynamic parameters of the prosthesis were determined by means of open cardiac catheterization and echocardiography intraoperatively and 2.5 years after operation respectively. The biocompatibility was evaluated by observing animal survival and valve thrombosis or thromboembolism.In result,all of the five sheep undergoing formal experiment survived well. There were no any prosthesis-related complications including mechanical valve failures, endocarditis, thrombosis, thromboembolism, and paravalvular leak. The transvalvular gradients were 5.2±1.7mmHg, 6.1±0.3mmHg and 6.8±0.4mmHg, the former was measured by catheterization intraoperatively, the two later were achieved by catheterization and echocardiography respectively 2.5 years after operation. The gradients increased mildly with the marked increase in cardiac output under dobutamine stress.The results of this study demonstrated that the JiuLing valve prosthesis has good biocompatibility and excellent hemodynamic performance.

Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus

Hippocampal neurons undergo various forms of cell death after status epilepticus.Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors.However,there are no reports of necroptosis in mouse models of status epilepticus.Therefore,in this study,we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus,and,furthermore,we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis.A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid,12 mg/kg.Different concentrations of necrostatin- 1 (10,20,40,and 80 μM) were administered into the lateral ventricle 15 minutes before kainic acid injection.Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining,western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins.Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy.The 40 μM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region.Furthermore,necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL,RIP1,and RIP3) and apoptosis-related proteins (cleaved-Caspase-3,Bax),and it upregulated the expression of anti-apoptotic protein Bcl-2.Taken together,our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus,with the 40 μM concentration of the compound having an optimal effect.The experiments were approved by the Animal Ethics Committee of Fujian Medical University,China (approval No.2016-032) on November 9,2016.

Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury

Ischemia-reperfusion (IR) injury represents a major cause of myocardial dysfunction after infarction and thrombolytic therapy, and it is closely related to the free radical explosion and overwhelming inflammatory responses. Herein, macrophage-targeting nanocomplexes (NCs) are developed to mediate efficient co-delivery of siRNA against MOF (siMOF) and microRNA-21 (miR21) into myocardial macrophages, cooperatively orches-trating the myocardial microenvironment against IR injury. Bioreducible, branched poly(β-amino ester) (BPAE-SS) is designed to co-condense siMOF and miR21 into NCs in a multivalency-reinforced approach, and they are surface-decorated with carboxylated mannan (Man-COOH) to shield the positive surface charges and enhance the serum stability. The final MBSsm NCs are efficiently internalized by myocardial macrophages after systemic administration, wherein BPAE-SS is degraded into small segments by intracellular glutathione to promote the siMOF/miR21 release, finally provoking efficient gene silencing. Thus, cardiomyocyte protection and macro-phage modulation are realized via the combined effects of ROS scavenging, inflammation inhibition, and autophagy attenuation, which ameliorates the myocardial microenvironment and restores the cardiac function via positive cellular crosstalk. This study renders promising solutions to address the multiple systemic barriers against in vivo nucleic acid delivery, and it also offers new options for IR injury by manipulating multiple reciprocal bio-reactions.

Total Arterial Revascularisation in Left Ventricular Dysfunction

The feasibility and safety of total arterial coronary revascularization with 2 arterial conduits in patients with impaired left ventricular function was evaluated. Data were prospectively collected on all patients with multiple vessel disease and moderately or severely impaired left ventricular function, who underwent coronary surgery with the intention of total arterial revascularization with 2 conduits between March 1995 and August 2002. One hundred and seventy-nine patients were included in the study. Acute coronary insufficiency was present in 3 patients and 43 had unstable angina. Severe left ventricular impairment was present in 29 patients. There were 17 redo operations including 3 redo-redo procedures. Eighty-two percent of patients had a Y graft configuration from the left internal mammary artery （right internal mammary artery 40. 8 %, radial artery 33. 5 %, other 7.8 % ）. The perioperative mortality was 2. 2 %, myocardial infarction 1.7 % and stroke 0. 6 %. Total arterial revascularization in patients with ischaemic left ventricular dysfunction can be safely performed with 2 arterial conduits. The radial artery provides conduit length greater than the right internal mammary artery and allows full revascularization despite left ventricular dilatation.

SARS-COV-2 Induce Pulmonary Injury from Basic to Clinical Research

The SARS-CoV-2 has infected over 194,909,000 cases and over 4,170,000 deaths in the world before the end of July 2021. The virus attacks human alveoli and induces severe lung injury (COVID-19 disease) and spreads rapidly. The mechanisms of COVID-19 disease are unclear. To better understand this disease, This review analyzes the SARS-CoV-2 biological characteristics, insights the effect of alveolar epithelium and its adjacent microvascular endothelium, investigates human host cells immune response and immunothrombosis. Explains clinical manifestations of COVID-19 associated lung injury. It may be helpful for development management strategies for COVID-19 associated pulmonary damage.

Uniportal versus biportal video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis

Background Video-assisted thoracoscopic sympathectomy had replaced open surgery. The aim of this study was to compare the outcomes of using a single port and two ports to perform video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis. Methods Between April 2006 and February 2008, 20 cases underwent video-assisted thoracoscopic sympathectomy through one port （uniportal group） and 25 cases through two ports （biportal group）. The variables including the operating time, hospital stay, pain scores, postoperative complications, incidence of symptom recurrence and patient satisfaction were compared. The mean postoperative follow-up period was 11.5 months （range, 3-25 months）. Results The hands of all patients were warm and dry after operation. No conversion to open surgery was necessary, and no operative mortality was recorded in either group. The mean inpatient pain scores were significantly higher in the biportal group （1.2±0.6） than that in the uniportal group （0.8±0.5, P=0.025）. For the first three weeks after operation, four out of 20 （20%） patients in the uniportal group constantly suffered from mild or moderate residual pain while eight out of 25 （32%） cases in the biportal group （P=0.366）. Among them, two cases in the uniportal group and five cases in the biportal group need to take analgesics. Our mean operative time （bilateral sympathectomy） in the uniportal group （（39.5±10.0） minutes） was shorter than that in biportal group （（49.7±10.6） minutes, P=0.02）. There were no significant differences between two groups in terms of the mean hospital stay, compensatory sweating, and patient satisfaction. Two patients in the biportal group and three in the uniportal group experienced a unilateral pneumothorax. None of them required chest drainage. No patient experienced Homer＇s syndrome, and no recurrent symptoms were observed in either groups Conclusions Both uniportal and biportal video-assisted thoracoscopic sympathectomy are effective, safe, and minimally invasive for palmar hyperhidrosis. Comparing with the biportal approach, the uniportal approach causes less postoperative pain and less operative time, and is a more reasonable procedure in treatment of palmar hyperhidrosis.

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB-P300-BRD4 axis

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis.Crosstalk between autophagy deficiency and inflammation response in foam cells(FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized lowdensity lipoprotein(ox-LDL) leads to abnormal crosstalk between autophagy and inflammation,thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4(BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation(LLPS) on the regulatory regions of inflammatory genes. Curcumin(Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway

Cellular senescence is closely associated with age-related diseases.Ovarian aging,a special type of organ senescence,is the pathophysiological foundation of the diseases of the reproductive system.It is characterized by the loss of integrity of the surface epithelium and a gradual decrease in the number of human ovarian surface epithelial cells(HOSEpiCs).To contribute to the research on delaying ovarian aging,we aimed to investigate the novel epigenetic mechanism of melatonin in protecting HOSEpiCs.We discovered that melatonin has antagonistic effects against the oncogene-induced senescence(OIS)of HOSEpiCs.Mechanistically,the oncogene Ras decreased the expression of YTHDF2,which is the reader of RNA-m6A,by stimulating the generation of reactive oxygen species(ROS).Moreover,we found that the suppression of YTHDF2 increased the expression of MAP2K4 and MAP4K4 by enhancing the stability of the transcription of their mRNAs,thereby upregulating the expression of the senescence-associated secretory phenotype(SASP)through the activation of the MAP2K4 and MAP4K4-dependent nuclear factor-κB(NF-κB)signaling pathways.We further determined that melatonin has antagonistic effects against the OIS of HOSEpiCs by inhibiting the ROS-YTHDF2-MAPK-NF-κB pathway.These findings provide key insights into the potential avenues for preventing and treating ovarian aging.