Immune-related Features of Esophageal Squamous Cell Carcinoma：A Multi-omics Perspective / 中山大学学报(医学科学版)

Esophageal squamous cell carcinoma is a common malignancy in the Asia-Pacific region， especially in China， where the morbidity remains high in spite of the improved overall survival due to advances in medical technology. Immunotherapy becomes a hot spot in recent tumor research when it has provided significant survival benefits in patients with advanced malignant tumors， such as lung cancer， breast cancer， colon cancer， etc. In esophageal squamous cell carcinoma， immunotherapy promotes survival benefit as well. However， because of the complex and changeable biological functions and gene expression regulation of malignant tumors， the conclusions based on a single-omics analysis are often incomprehensive. Currently， most of the immune-related studies on esophageal squamous cell carcinoma are still confined to a single-omics study like genomics， with limitations and one-sidedness. Since multi-omics analysis helps us better understand tumors from a wider and deeper perspective， this review explores and summarizes immune-related features of esophageal squamous cell carcinoma from a multi-omics perspective.

Preservation with high-pressure carbon monoxide better protects ex vivo rabbit heart function than conventional cardioplegic solution preservation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the protective effect of high-pressure carbon monoxide for preservation of ex vivo rabbit heart graft in comparison with the conventional HTK cardioplegic solution preservation.</p><p><b>METHODS</b>Heart grafts isolated from 85 New Zealand rabbits were randomly divided into Naive group (n=5), HTK group (n=40) and CO group (n=40). The grafts underwent no preservation procedures in Naive group, preserved at 4 degrees celsius; in HTK cardioplegic solution in HTK group, and preserved at 4 degrees celsius; in a high-pressure tank (PO2: PCO=3200 hPa: 800 hPa) in CO group with Krebs-Henseleit solution perfusion but without cardioplegic solution. After preservation for 2, 4, 6, 8, 10, 14, 18, and 24 h, 5 grafts from the two preservation groups were perfused for 30 min with a modified Langendorff apparatus and examined for left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), arrhythmia score (AS), myocardial ultrestructure, and cardiac enzyme profiles.</p><p><b>RESULTS</b>After preservation for 6 to 24 h, the cardiac enzyme profiles and systolic and diastolic functions were significantly better in CO group than in HTK group, but these differences were not obvious between the two groups after graft preservation for 2 to 4 h. Significant changes in the myocardial ultrastructures occurred in the isolated hearts after a 24-h preservation in both CO and HTK groups, but the myocardial damages were milder in CO group.</p><p><b>CONCLUSION</b>Preservation using high-pressure carbon monoxide can better protect isolated rabbit heart graft than the conventional HTK preservation approach especially for prolonged graft preservation.</p>

Expression and functional role of small conductance Ca(2+)-activated K(+) channels in human atrial myocytes / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression and functional role of the small conductance Ca(2+)-activated K(+) channels in human atrial myocytes.</p><p><b>METHODS</b>We collected the right atrial appendage tissues from 8 patients with congenital heart defect with sinus rhythm undergoing open-heart surgery. Immunohistochemistry was performed to identify the expression of 3 isoforms of SK channel (SK1, SK2 and SK3). Using the classical two-step enzymatic isolation method, perforated patch clamp and conventional voltage-clamp techniques were performed to record the action potentials (APs) and the whole-cell Ca(2+)-activated K(+) current (I(K, Ca)) in the single atrial myocyte. We compared the changes in action potential duration (APD) before and after the application of a specific SK channels blocker apamin (100 nmol/L).</p><p><b>RESULTS</b>Human atrial myocytes showed positivity for all the SK1, SK2 and SK3 isoform channels. Patch-clamp recording confirmed the presence of I(K,Ca), and apamin significantly prolonged APD at 90% repolarization (APD(90)), but produced no obvious effect on APD(50).</p><p><b>CONCLUSION</b>The three isoforms of SK channels are all expressed in human atrial myocytes. SK channels play a prominent role in the late phase of repolarization in human atrial myocytes, which is distinct from their functional roles in neurons where they mediate the process of afterhyperpolarization following APs.</p>

Early surgical outcomes of coronary heart disease with severe ischemic mitral regurgitation / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the experience with surgical treatment of coronary artery disease with severe ischemic mitral valve regurgitation (IMR).</p><p><b>METHODS</b>From January 2006 to December 2009, 45 patients (35 males, 10 females aged 32-74 years) with the diagnosis of coronary artery disease complicated by IMR underwent coronary artery bypass grafting (CABG) combined with mitral valve plasty (MVP, 24 cases) or mitral valve replacement (MVR, 21 cases).</p><p><b>RESULTS</b>Perioperative deaths occurred in 2 cases due to multiple organ failure (MOF). Echocardiography showed a significant reduction of the mitral regurgitation area (from 11.80∓2.45 cm(2) to 2.83∓0.98 cm(2), t=22.80, P=0.00) after CABG combined with mitral valve surgery, with also significantly reduced postoperative left ventricular end diastolic diameter (LVEDD) (from 57.61∓10.06 mm to 51.84∓8.98 mm, t=2.85, P=0.005). No significant difference was detected in the left ventricular ejection fraction after the operation [(52.7∓15.4)% vs (53.2∓13.2)%, t=0.16, P=0.87)].</p><p><b>CONCLUSIONS</b>CABG combined with mitral valve surgery can improve early postoperative left ventricular function in patients with ischemic coronary heart disease complicated by severe mitral regurgitation, but further follow-up study is still needed for evaluation of the long-term results.</p>

Screening and identification of auto-antigen RHDAG1 of rheumatic heart disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease.</p><p><b>METHODS</b>The total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed.</p><p><b>RESULTS</b>The phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3×10(6) pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of patients with active rheumatic fever and of those with rheumatic heart disease, but not in the serum of healthy subjects.</p><p><b>CONCLUSION</b>Phage display library can be an effective strategy to screen the auto-antigens of rheumatic heart disease. The auto-antigen RHDAG1 can be a candidate molecular biomarker of rheumatic heart disease and/or rheumatic fever.</p>

Clinical application of low-molecular-weight heparin (Fraxiparine) in rescuing venous crisis of island skin flap / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of low molecular weight heparin (Fraxiparine) in rescuing venous crisis of island skin flap.</p><p><b>METHODS</b>Of the 73 patients with venous crisis of island skin flap, 47 received subcutaneous injection of low-molecular-weight heparin (group I) and 26 were treated with phlebotomy, local compression and topical application of unfractionated heparin solution gauze (group II).</p><p><b>RESULTS</b>The flap survival ratio was (88.46∓8.64)% in group I and (38.37∓6.53)% in group II (P<0.001). At 0, 2, and 4 h after injection of low-molecular-weight heparin, the activated partial thromboplastin time (APTT) was obviously delayed (24.28∓6.71, 41.35∓7.64 and 32.34∓6.35, respectively, P<0.01), FXa:C level was significantly decreased (152.4∓30.7, 65.8∓24.4 and 83.4∓18.4, respectively, P<0.01), while FIIa:C level underwent no obvious alterations (155.70∓31.61, 143.20∓24.75, and 143.4∓23.35, respectively, P=NS).</p><p><b>CONCLUSION</b>Fraxiparine has good antithrombotic efficacy in rescuing venous crisis of island skin flap without adverse effect on systemic coagulation.</p>

Surgical treatment of 128 cases of constrictive pericarditis / 南方医科大学学报

<p><b>OBJECTIVE</b>To summarize the experience with surgical treatment of constrictive pericarditis.</p><p><b>METHODS</b>A retrospective analysis of the post-operative clinical data was conducted in 128 surgical patients with chronic constrictive pericarditis.</p><p><b>RESULTS</b>Two early postoperative death occurred in this group due to severe low cardiac output syndrome, with the mortality rate of 1.57%. The postoperative complications included low cardiac output syndrome (13.2%), arrhythmia (7.02%), acute renal insufficiency (3.9%), respiratory insufficiency (3.1%), wound infection (2.3%), postoperative chest bleeding (1.6%) and cerebral infarction (0.78%). Relapse occurred in one case because of incomplete pericardial resection.</p><p><b>CONCLUSIONS</b>Constrictive pericarditis should be confirmed as soon as possible with actively surgery, and the extent of pericardial resection should be decided according to the individual conditions. Complete untethering of the diseased pericardium should be performed with active prevention of postoperative complications.</p>

Early and mid-term results after 17 mm St Jude Regent mechanical valve replacement in 44 patients with small aortic root / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the changes in the cardiac function after St. Jude Regent mechanical valve replacement and assess the prosthesis-patient matching.</p><p><b>METHODS</b>From October 2007 to March 2009, 44 patients received implantation of 17 mm St. Jude aortic prostheses in our hospital. The patients were followed up for clinical symptoms, signs, electrocardiogram (ECG), echocardiogram and cardiac functions, and the results were compared with those of randomly selected 44 patients receiving 21 mm St. Jude aortic prostheses.</p><p><b>RESULTS</b>In 17 mm St Jude Medica Regent valve group, 8 patients presented with ECG ST segment changes, 3 complained of chest tightness, 3 had occasional chest pain and discomfort, and 8 had grade II and 4 grade III cardiac function. In 21 mm St Jude Medical Regent valve group, 6 patients had ECG ST segment changes, 2 complained of chest tightness, 2 reported occasional chest pain and discomfort, 11 had grade II and 2 grade III cardiac function. No significant differences were found in these indices between the two groups (P=0.32). Compared with those before operation, the two groups showed significant improvements in the left ventricular end-diastolic diameter, left ventricular posterior wall thickness, left ventricular mass index, and aortic pressure gradient (P<0.05). A significant increase in the left ventricular ejection fraction occurred 6-12 months after operation, but without statistical difference between the two groups (P>0.05).</p><p><b>CONCLUSION</b>For underweight patients (<60 kg) and those with small body surface area (<1.6 cm(2)), 17 mm St. Jude Medical Regent valve prosthesis may produce good therapeutic effect, and some indices are even close to those after placement of 21 mm St. Jude Medical Regent valve prosthesis. No obvious prosthesis-patient mismatch occurs after the placement of the 17 mm valve prosthesis and aortic valve ring expansion is not necessary.</p>

Establishment of a rat model of bone marrow mesenchymal stem cell transplantation for repairing full-thickness skin defect / 南方医科大学学报

<p><b>OBJECTIVE</b>To establish a rat model of full-thickness skin defect to receive bone marrow mesenchymal stem cell transplantation for wound repair.</p><p><b>METHODS</b>A full-thickness skin defect measuring 4 cmx4 cm in 36 F344 rats, which were divided into 3 groups with the wound covered with alloskin graft, acellular dermal matrix, or petrolatum gauze. In vitro cultured BMSCs in the 5th passage were transplanted into the skin defect, and the time of wound dressing dissociation and number of transplanted Brdu-positive cells in the wound were observed 14 days later.</p><p><b>RESULTS</b>The alloskin graft resulted in significantly longer time before dressing dissociation, with greater number of Brdu-positive cells in the wound than the other two wound dressings (P<0.001). The acellular dermal matrix showed better effect than petrolatum gauze in terms of the dressing dissociation time and the viable transplanted cell number in the wound.</p><p><b>CONCLUSION</b>Alloskin graft can be ideal for covering the wound surface to protect the transplanted BMSCs in rats.</p>

Transepicardial autologous transplantation of bone marrow mononuclear cells for acute myocardial infarction / 南方医科大学学报

<p><b>OBJECTIVE</b>To test the effect of intramyocardial injection of autologous bone marrow mononuclear cells (MNCs) in improving the cardiac function and myocardial revascularization in miniswine models of myocardial infarction.</p><p><b>METHODS</b>The miniswine models of myocardial infarction established by ligation of the anterior descending coronary artery were divided into 3 groups including a control and two MNC injection groups. Autologous bone marrow MNCs were injected via the epicardium into the infarcted area in the latter two groups at 1 and 2 weeks after the infarction, respectively. The ventricular segmental wall motion was evaluated after the treatment, and the infarcted myocardium observed with immunohistochemistry on frozen sections.</p><p><b>RESULTS</b>The left ventricular segmental wall motion differed significantly between the control and the MNC injection groups at 1 and 2 months after the treatment. CM-DiI-positive cells were detected in the infarcted myocardium where MNCs were implanted.</p><p><b>CONCLUSION</b>Intramyocardial injection of autologous bone marrow MNCs improves the infarcted ventricular segmental wall motion, and significantly increases the number of blood vessels in the infracted area. The transplanted cells can be integrated into the vascular walls of the capillaries and arterioles and differentiate into cardiomyocytes.</p>

Perivenous support with autologous pericardium inhibits neointimal thickening in canine vein grafts / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of perivenous support with autologous pericardium on neointimal thickening in canine vein grafts.</p><p><b>METHODS</b>An autologous pericardium graft of 7 cm x 4 cm was harvested in right anterolateral thoracotomy. Two equal segments of the jugular vein were transplanted to both sides of the femoral arteries in 12 dogs, and on one side of the vein graft, perivenous support with autologous pericardium was applied. The vein grafts were harvested 2 and 4 weeks after operation and the thickness and area of the neointima calculated using computerized image analysis system. Scanning electron microscopy and PCNA immunohistochemistry were also performed.</p><p><b>RESULTS</b>The thickness and area of the neointima were significantly greater in the control grafts than in the grafts with perivenous support (P<0.05), and the proliferation of vascular smooth muscle cells in the supported graft was less active (P<0.05). Electron microscopy showed extensive destruction of the endothelium in the control graft, but only slight damage was found in the graft with perivenous support.</p><p><b>CONCLUSION</b>Perivenous support of the vein graft with autologous pericardium can reduce intimal and medial hyperplasia in the graft.</p>

Clinical analysis of gastrointestinal bleeding after cardiac surgery / 中华外科杂志

<p><b>OBJECTIVE</b>To explore early diagnosis, treatment and prevention of gastrointestinal (GI) bleeding after cardiac surgery.</p><p><b>METHODS</b>In the last 13 years, cases complicated with GI bleeding after cardiac surgeries were analyzed retrospectively.</p><p><b>RESULTS</b>Fourty-four GI bleeding occurred post-operatively in (6 +/- 3) d. The mortality was 23% (10/44). Thirty-eight were located in upper GI tract, of them 26 underwent conservative therapy while 4 died of other than GI bleeding cause; six underwent laparotomy while 1 and 3 died of septicemia and multi-organ failure respectively; six underwent gastric endoscopic hemostasis by electrocautery or clipping the bleeding vessel while all survived. Six were located in lower GI tract, and 2 of them underwent laparotomy without finding bleeding section and died of multi-organ failure. By multivariable logistic regression analysis, deaths were highly related to the post-operative ventilator-dependence, acute renal insufficiency, intra-aortic balloon pump (IABP) assisting and laparotomy.</p><p><b>CONCLUSION</b>The mortality of GI bleeding after cardiac surgeries is very high, early gastrointestinal endoscopic examination and minimally invasive intervention can treat this complication more effectively. GI bleeding must be prevented whenever complicating post-operative ventilator-dependence, acute renal insufficiency, and IABP assisting after cardiac surgery.</p>