[Interpretation on Expert systematic review on the choice of conduits for coronary artery bypass grafting endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons in 2023].

Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons published in 2023 made recommendations for the selection of bypass vessels. The left internal thoracic artery-anterior descending branch anastomosis represents the accepted gold standard. Radial artery could achieve a better long-term patency rate and a reduction in adverse cardiac events compared to the great saphenous vein. Radial artery graft using an open harvesting method should be chosen to graft the target vessel with low competitive coronary flow, with the use of vasodilators for the first year. There was no clear evidence of better patency for the right internal thoracic artery compared to the great saphenous vein. The bilateral internal thoracic artery had better long-term survival compared to great saphenous vein but may be associated with a higher risk of deep sternal wound infection and should be avoided in high-risk patients. The impact of skeletonization of the internal thoracic artery on graft patency and cardiovascular outcomes was unclear. Endoscopic vein harvest reduced the risk of leg wound complications and was associated with reduced long-term patency. The patency of the no-touch great saphenous vein was significantly better than that of conventional great saphenous vein. A significantly higher risk of complications at the harvesting site and no clear evidence of better long-term clinical outcomes were found in the no-touch great saphenous vein compared to the conventional. There was limited data on the use of right gastroepiploic artery and skeletonized harvesting, which should be used to bypass target vessels in patients with low competitive flow.

[Effect analysis of myectomy guided by personalized three-dimensional reconstruction and printing in the treatment of obstructive hypertrophic cardiomyopathy].

Objective: To examine the clinical efficacy of myectomy guided by personalized three-dimensional reconstruction and printing for patients with obstructive hypertrophic cardiomyopathy. Methods: The clinical data of 28 patients with obstructive hypertrophic cardiomyopathy, who underwent septal myectomy guided by personalized three-dimensional reconstruction and printing in the Department of Cardiaovascular Surgery, Guangdong Provincial People's Hospital from May 2020 to December 2021, were retrospectively analyzed. There were 14 males and 14 females, aging (51.1±14.0) years (range: 18 to 72 years). Enhanced cardiac computed tomography images were imported into Mimics software for preoperative three-dimensional reconstruction. The direction of the short axial plane of each segment was marked perpendicularly to the interventricular septum on the long axial plane of the digital cardiac model, then the thickness was measured on each short axial plane. A figurative digital model was used to determine the extent of resection and to visualize mitral valve and papillary muscle abnormalities. Correlation between the length, width, thickness, and volume of the predicted resected myocardium and those of the surgically resected myocardium was assessed by Pearson correlation analysis or Spearman correlation analysis. The accuracy of detecting mitral valve and papillary muscle abnormalities of transthoracic echocardiography and three-dimensional reconstruction was also compared. Results: There was no death or serious complications like permanent pacemaker implantation, re-sternotomy for bleeding, low cardiac output syndrome, stroke, or multiple organ dysfunction syndromes in the whole group. Namely, the obstruction of the left ventricular outflow tract was effectively relieved. The systolic anterior motion of the anterior mitral valve leaflet was absent in all patients after myectomy. The length, width, and thickness of the predicted resected myocardium by three-dimensional reconstruction were significantly positively correlated with the length (R=0.65, 95%CI: 0.37 to 0.82, P<0.01), width (R=0.39, 95%CI: 0.02 to 0.67, P<0.01), and thickness (R=0.82, 95%CI: 0.65 to 0.92, P<0.01) of the surgically resected myocardium, while the relation of the volume of the predicted resected myocardium and the volume of the surgically resected myocardium was a strong positive correlation (R=0.88, 95%CI: 0.76 to 0.94, P<0.01). Importantly, the interventricular septal myocardial thickness measured by preoperative transthoracic echocardiography showed a moderate positive correlation with the volume of surgically resected myocardium (R=0.52, 95%CI: 0.19 to 0.75, P<0.01). During a follow-up of (14.4±6.8) months (range: 3 to 22 months), no death occurred, and 1 patient was readmitted for endocardial radiofrequency ablation due to atrial fibrillation. Conclusion: Personalized three-dimensional reconstruction and printing can not only visualize the intracardiac structure but also guide septal myectomy by predicting the thickness, volume, and extent of resected myocardium to achieve ideal resection.

[Surgery for obstructive hypertrophic cardiomyopathy: challenge and future].

After more than 60 years of development, with the deepening of the pathophysiological understanding of obstructive hypertrophic cardiomyopathy, the extent and resection thickness of myectomy have increased significantly. Myectomy combined with the correction of anomalies of the mitral valve apparatus has become the standard treatment of obstructive hypertrophic cardiomyopathy. Only a few centers worldwide can routinely perform it due to the difficulty. Because of the advances of new drugs and interventional therapy, the development of surgical treatment faces many challenges. At the same time, generations of cardiovascular surgeons are constantly trying to promote septal myectomy, including developing devices and the surgical field, as well as improving surgical planning by advanced technology. At present, the superior long-term efficacy of septal myectomy has been confirmed. It is necessary to work together to promote the treatment of hypertrophic obstructive cardiomyopathy, so as to guard people's health.

[Early outcomes of thoracoscopic trans-mitral myectomy in obstructive hypertrophic cardiomyopathy patients with left midventricular obstruction].

Objective: To examine the early effect of thoracoscopic trans-mitral myectomy for hypertrophic cardiomyopathy patients with left midventricular obstruction. Methods: From April 2020 to July 2021, 10 hypertrophic cardiomyopathy patients with left midventricular obstruction underwent thoracoscopic trans-mitral myectomy at Guangdong Provincial People's Hospital. The whole group of patients consisted of 7 males and 3 females aged (52.0±16.4) years (range: 18 to 68 years). The EuroSCORE Ⅱ predicted mortality rate was 1.78% (1.20%) (M(IQR)) (range: 0.96% to 4.86%). The clinical data were collected and analyzed retrospectively to evaluate the clinical efficacy by comparing preoperative and postoperative echocardiographic parameters using paired t-test, paired Wilcoxon test or Fisher exact test, including left ventricular outflow tract peak pressure gradient, maximum interventricular septum thickness, systolic anterior motion of the anterior mitral leaflet and so on. The safety was determined by summarizing the incidence of perioperative and follow-up complications. Results: All the procedures successed with no conversion to median sternotomy, septal defect, ventricular rupture. There was no in-hospital 30-day death, neither serious complications like permanent pacemaker implantation, re-sternotomy for bleeding, low cardiac output syndrome, stroke, or multiple organ dysfunction syndrome. The left ventricular outflow tract obstruction was effectively relieved in all patients expect a patient developed residual obstruction. Compared with that of pre-operation, the thickness of the interventricular septum was significantly reduced from (22.1±4.0) mm to (10.3±1.7) mm (t=10.693, P<0.01), while the left ventricular outflow tract peak pressure gradient was significantly reduced from (81.7±21.1) mmHg to 12.3 (11.5) mmHg (Z=-2.805, P<0.01) (1 mmHg=0.133 kPa). Conclusion: Thoracoscopic trans-mitral myectomy is an effective and safe procedure for hypertrophic cardiomyopathy patients with left midventricular obstruction.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

The article "LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p, by M.-M. Wu, W.-D. Shen, C.-W. Zou, H.-J. Chen, H.-M. Guo, published in Eur Rev Med Pharmacol Sci 2020; 24 (11): 6031-6038-DOI: 10.26355/eurrev_202006_21497-PMID: 32572917" has been withdrawn from the authors due to some technical issues in the data retrieval. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21497.

[Interpretation of the American Association for Thoracic Surgery expert consensus document: coronary artery bypass grafting in patients with ischemic cardiomyopathy and heart failure in 2021].

An expert consensus on coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM) was released by the American Association for Thoracic Surgery in May 2021, which contains a vast array of perioperative recommendations. During preoperative period, a comprehensive assessment on ICM including myocardial viability and valve function by a multi-disciplinary team (MDT) approach should be performed. In terms of intraoperative period, multiple arterial conduits and on-pump CABG using cold blood cardioplegia should be considered, meanwhile, other aspects involving concomitant management of mitral valve regurgitation and arrythmia, as well as active use of mechanical cardiac assist devices (e.g., intra-aortic balloon pump) should also be achieved. Finally, a range of postoperative interventions which includes standardized MDT management in intensive care unit (ICU), continuous use of cardiac assist devices, cardiac pacing, close follow-up within 90 days and drug treatment strictly guided by the guidelines after discharge from hospital should be conducted. The above-mentioned perioperative bundled care might reduce perioperative complications and operative mortality, and thus improve the prognosis of the patients with ICM.

MicroRNA-203a-3p affects the biological characteristics of nasopharyngeal carcinoma by targeting vascular endothelial growth factor-C.

Nasopharyngeal carcinoma (NPC) has a high incidence in Southeast Asia and China. This study aims to investigate the effect of miR-203a-3p and vascular endothelial growth factor-C (VEGF-C) on nasopharyngeal carcinoma. In this study, we investigate the transfection of miR-203a-3p mimics and the ability of miR-203a-3p to inhibit in nasopharyngeal carcinoma cell line 5-8F and C666-1, the expression levels of protein AKT, p-AKT in VEGF-C and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signal pathway by plate clone formation experiment, flow cytometer PI staining method, transwell cell experiment, vasculogenic mimicry experiment, and Western blot. The results showed that miR-203a-3p in the nasopharyngeal carcinoma cell line significantly decreased, while VEGF-C in nasopharyngeal carcinoma tissues and cell lines significantly increased. Furthermore, miR-203a-3p inhibited the proliferation of nasopharyngeal carcinoma cells and blocked the cell cycle of nasopharyngeal carcinoma in the G0/G1 phase, reduced the vasculogenic phenomena and epithelial-mesenchymal transition of nasopharyngeal carcinoma cells, and effectively inhibited the growth of nasopharyngeal carcinoma in vivo. The low expression of VEGF-C can inhibit the proliferation, vasculogenic mimicry, and epithelial-mesenchymal transition of nasopharyngeal carcinoma cells. We found that miR-203a-3p was expressed to a low degree in nasopharyngeal carcinoma. Furthermore, miR-203a-3p regulated the PI3K/AKT signal pathway by downregulating the expression of VEGF-C, thereby inhibiting the proliferation, migration, invasion, vasculogenic mimicry, epithelial-mesenchymal transition, and other malignant biological characteristics of nasopharyngeal carcinoma cells.

LncRNA-HEIH suppresses hepatocellular carcinoma cell growth and metastasis by up-regulating miR-199a-3p.

OBJECTIVE: The aim of this study was to explore the functional changes of long non-coding ribonucleic acid (lncRNA)-HEIH on hepatocellular carcinoma (HCC) Huh7 and Hep3B cells. PATIENTS AND METHODS: The expression changes of HEIH in 18 pairs of HCC tissues and adjacent normal tissues were detected by quantitative real time-polymerase chain reaction (qRT-PCR). According to its expression changes in HCC cells silenced by short hairpin ribonucleic acid (shRNA) transfection in vitro, these cells were divided into sh-HEIH group and sh-NC group. The effects of lowly expressed HEIH on the proliferation, migration and apoptosis of HCC cells were examined through functional assays. Western blotting was adopted to determine the expression changes of epithelial-mesenchymal transition (EMT) proteins, vimentin, matrix metalloproteinase (MMP)-2 and MMP-3. In addition, the role of HEIH downstream effector micro RNA (miR)-199a-3p in HCC was explored. RESULTS: Compared with adjacent normal tissues, HEIH was highly expressed in HCC tissues (p<0.01). HEIH silencing significantly inhibited the proliferation and migration, but induced the apoptosis of Huh7 cells (p<0.05). The expressions of vimentin and MMP-2 in sh-HEIH group were remarkably lower than those in sh-NC group (p<0.05). Furthermore, miR-199a-3p was identified as the downstream effector of HEIH. The expression of miR-199a-3p increased markedly in Huh7 and Hep3B cells with silenced HEIH expression (p<0.01). Moreover, when miR-199a-3p expression was inhibited, the effects of HEIH on Huh7 and Hep3B cells were weakened, manifested as notably enhanced cell proliferation and migration capabilities (p<0.05). CONCLUSIONS: LncRNA-HEIH suppresses HCC cell growth and metastasis by up-regulating miR-199a-3p. Our findings suggest that HEIH may be a promising target for HCC treatment.

Clinical significance of SLP-2 in epithelial ovarian cancer and its regulatory effect on the Notch signaling pathway.

OBJECTIVE: To explore the expression of Stomatin-like protein 2 (SLP-2) and its clinical significance in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the differential expression of SLP-2 in EOC tissues and cell lines. The relationship between SLP-2 expression and clinical pathological data of EOC patients was analyzed. RESULTS: QRT-PCR results suggested that the SLP-2 was up-regulated in both EOC tissues and EOC cells by comparing with normal control. SLP-2 expression was a correlation with tumor pathological grade, distant metastasis, and TNM stage in EOC patients. Down-regulation of SLP-2 could significantly inhibit proliferation and promote apoptosis of EOC cells by activating the Notch signaling pathway. Knockdown of SLP-2 markedly downregulated Notch1 and Hes1. CONCLUSIONS: SLP-2 was a novel factor involved in EOC progression, and could be utilized as a potential biomarker and therapeutic target for the EOC patients.

[The mid-term outcomes of minimally invasive plasty for severe tricuspid regurgitation after cardiac surgery].

Objectives: To evaluate the efficacy of minimally invasive surgery in patients with late severe tricuspid regurgitation after cardiac surgery, and to evaluate the role of leaflets augmentation technique in tricuspid valvuloplasty. Methods: From January 2015 to June 2019, 85 patients undergoing tricuspid valve repair procedure with minimally invasive approach at Department of Cardiovascular Surgery, Guangdong provincial People's Hospital were enrolled. There were 22 males and 63 females, aging of (53.6±12.4) years (range: 15 to 75 years). The interval between the prior and current operations was (16.0±7.3) years (range: 0.2 to 35.0 years). The diameter of right atrium and right ventricle was (77.3±17.2) mm and (61.0±8.4) mm, respectively. Tricuspid regurgitation was severe or extremely severe, the tricuspid regurgitation area was (19.0±10.3) cm(2). All patients underwent minimally invasive tricuspid valvuloplasty or tricuspid valve replacement on beating-heart with totally endoscopic technique and port-access approach through right chest wall. The operations included tricuspid valve replacement and tricuspid valvuloplasty, the technique of tricuspid valvuloplasty including leaflets augmentation with patch, ring implantation, chordae tendineaes reconstruction, release of papillary muscle, edge to edge method, etc. Postoperative hospitalization days, the time of ICU stay, blood transfusion rate, ventilator time and the results of echocardiography were recorded. Follow-up was completed regularly by WeChat, telephone and outpatient visit. Results: Sixty-five patients underwent tricuspid valve repair, and 20 patients underwent tricuspid valve replacement because of prosthetic failure and plasty failure. Five patients died during hospitalization, with mortality rate 5.9%. One patient was transferred to local hospital for anti-infection treatment, the other 79 patients were discharged from hospital in well condition and followed-up. The postoperative hospitalization time was 7.0 (5.5) days (M(Q(R))) days, the mean ventilator time was 18.0 (16.2) hours, and the mean ICU stay time was 68.0 (75.5) hours. There were 35 patients without blood conduction transfusion, the transfusion rate was only 58.9% (50/85). Four cases of severe, 9 cases of moderate and 67 cases of mild to zero tricuspid regurgitation were examined before being discharged, with tricuspid regurgitation area of (2.8±3.5) cm(2) (range: 0 to 19.1 cm(2)). The follow-up time was 1 to 38 months. Two patients died during follow-up, one patient died from infective endocarditis and mitral perivalvular leakage, the other one died of intractable right heart failure. One patient was implanted with permanent pacemaker due to Ⅲ atrioventricular block. Valvular re-replacement was performed in 2 patients who were re-admitted for the artificial valve infection and mechanical valve obstruction. No re-operation of tricuspid valve. Conclusions: Totally endoscopic minimally invasive technique provided satisfactory surgical outcomes for critically sick patients with severe tricuspid regurgitation following cardiac surgery. The application of leaflets augmentation technique achieved ideal repair effect for previously unrepairable lesions.

LncRNA NEAT1 regulates cervical carcinoma proliferation and invasion by targeting AKT/PI3K.

OBJECTIVE: Cervical cancer is a common tumor in gynecological malignancies. Recent studies showed that long non-coding RNAs (lncRNAs) play a key role in tumorigenesis and development. LncRNA nuclear-rich transcripts 1 (NEAT1) has been found to play a role in gynecological tumors, such as endometrial cancer. However, expression of lncRNA NEAT1 and mechanism in cervical cancer has not been elucidated. MATERIALS AND METHODS: The tumor tissue and adjacent tissue of cervical cancer patients were collected. HeLa cells were cultured in vitro and lncRNA NEAT1 expression was interfered with small interfere RNA (siRNA). Cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Cell invasion ability was assessed by transwell assay. LncRNA NEAT1, Cyclin D1, and cyclin-dependent kinase 4 (CDK4) expressions were detected by Real-time PCR. Caspase 3 expression was detected by caspase 3 activity kit. Phosphorylated protein kinase B (p-AKT), phosphatidylinositol 3-kinase (p-PI3K), and matrix metalloproteinase-2 (MMP2) levels were evaluated by Western blot. RESULTS: Compared with the adjacent tissue, lncRNA NEAT1 expression was significantly increased in cervical cancer (p<0.05). LncRNA NEAT1 level was decreased in HeLa cells transfected by siRNA, which inhibited the proliferation and invasion of tumor cells, reduced cyclin D1 and CDK4 expressions, enhanced caspase 3 activity, and declined the expressions of p-AKT, p-PI3K, and MMP2 (p<0.05). CONCLUSIONS: LncRNA NEAT1 siRNA transfection can inhibit the proliferation of cervical cancer by regulating the AKT/PI3K signaling pathway, promote cell apoptosis, and restrain cell invasion. Therefore, the lncRNA NEAT1 may be used as a molecular potential for the diagnosis and treatment of cervical cancer through regulating AKT/PI3K signaling pathway, which would be confirmed in the following study.

[Clinical analysis of endoscopic endonasal approach for removal of sellar tumors].

Objective:To investigate the safety and efficacy of endoscopic endonasal approach for removal of sellar tumors. Method: The clinical data of 18 patients with sellar tumors undergoing endoscopic endonasal surgery were analyzed retrospectively. This series consisted of ten pituitary adenomas, five craniopharyngiomas, three meningiomas. The headache, visual improvement, endocrine, extent of resection and surgical complications were evaluated. Result:Total removal was achieved in 14 patients (77.8%), almost total removal was achieved in one patient of pituitary adenoma with two craniopharyngiomas (16.7%), and one patient with the subtotal removal of craniopharyngioma (5.6%) received gamma knife therapy. Overall, 18 patients with headache got improved obviously; 15 patients presented with visual and view impairment, All of them, vision and view were improved or even recovered to normal following surgery; There were 2 new cases of postoperative diabetes insipidu; 5(27.8%) patients had hyposmia after operation; 1 patient (5.6%) with adenoma suffered cerebrospinal fluid rhinorrhea, the second operation was successful. The follow-up lasted 12-84 months, no tumor recurrence was identified by MRI examination, and no patient died. Conclusion:The endoscopic endonasal approach is feasible and safe for the treatment of tumors in the sellar region. With advantages of clear vision, better exposure, without brain retraction, and preservation of vascular and neurological function. Skilled endoscopic technique and reliable skull base reconstruction are important to ensure success of surgery.

A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.

[Clinical experience of 60 patients underwent three-dimensional video assisted thoracoscopic mitral valvuloplasty].

OBJECTIVE: To summarize the clinical experience of 60 patients underwent three-dimensional video assisted thoracoscopic mitral valvuloplasty. METHODS: Sixty patients were enrolled retrospectively from March 2014 to January 2016 in Department of Cardiacvascular Surgery, Guangdong Cardiovascular Institute. They underwent three-dimensional video assisted thoracoscopic mitral valvuloplasty. There were 37 male and 23 female patients. The range of age was 15 to 78 years (the median age was 47 years). The techniques of mitral valvuloplasty included chordae tendineae transplantation (53 patients), annuloplasty (58 patients), posterior leaflet resection (13 patients), anterior leaflet resection (2 patients), commissure resection (1 patient). Their information from charts were collected. The follow-up time was lasting 3 to 25 months by telephone or outpatient department interview. The data was analyzed via paired t test or Wilcoxon signed-rank test. RESULTS: Conversions to mitral valve replacement were performed for two patients. No patients underwent thoracotomy. The operation time was (213±37) minutes, cardiopulmonary bypass time was (129±31) minutes, aortic cross clamping time was (81±21) minutes. Postoperative hospital stay was (7±3) days. During follow-up period, there were no re-operation and no death. Mitral regurgitation level and New York Heart Association class were both improved (Z=-6.286, P=0.000, Z=-6.237, P=0.000), respectively. Besides, there was also no new atrial fibrillation patients. CONCLUSIONS: Not only does three-dimensional video assisted thoracoscopic mitral valvuloplasty maintain the advantages of 2-Dimensional thoracoscopy, but also have the similar view of median thoracotomy. This technique showed promising clinical value in the future.

[Recent and long-term hearing outcomes in the cases after open tympanoplasty using titanium ossicular prosthesis].

Objective:To analyze recent and long-term hearing outcomes of the patients with chronic otitis media after open tympanoplasty using titanium ossicular prosthesis. Method:Retrospectively analyzed total 84 cases after open tympanoplaty with titanium ossicular prosthesis. The hearing outcomes before and after surgery(6 months and 24 months) were compared. Result:The hearing levels in the cases were improved to different degrees after surgery.Significant differences were showed compared the average pure tone threshold/air bone gap before surgery with the average recent/long-term outcomes after surgery(P<0.01),and no significant difference could be found compared the recent and long-term outcomes after surgery. Conclusion:Hearing level could be improved in the patients after open tympanoplasty using titianium ossicular prosthesis,and the long-term outcome could be steady.

Effect of low temperatures on BAX and BCL2 proteins in rats with spinal cord ischemia reperfusion injury.

We evaluated changes in BAX and BCL2 expression levels after spinal cord ischemia/reperfusion injury (SCII) and hypothermia during operations in rats. Eighty rats were divided into four groups: Group A (N = 20, 18°C); Group B (N = 20, 28°C); Group C (N = 20, room temperature); and Group D (N = 20, sham operation control). Spinal cord ischemia was induced for 90 min. Hypothermia was induced 15 min before, and maintained during ischemia, followed by heating to normothermia for 30 min after reperfusion. Motor function of the lower limbs was evaluated according to the Tarlov score at 72 and 168 h. For each rat, spinal cord samples were taken at 6, 24, 72 h, and 1 week to evaluate the histopathological changes, neuronal apoptosis, and BAX and BCL2 expression levels. Compared with normothermia, hypothermia significantly improved hind limb function; Group B achieved a higher score than Group A. Group D showed no neurologic deficiency, while the other groups showed various degrees. Group C exhibited greater neuronal apoptosis, higher BAX expression, but lower BCL2 expression than the other groups. Compared with Group A, BAX was expressed less and BCL2 more in Group B, and there was less apoptosis in Group B. Hypothermia preserves hind limb motor function and reduces neuronal death, thereby protecting rats from SCII. The spinal cord may be protected from SCII by inhibition of BAX and activation of BCL2. However, deep hypothermia may inhibit the expression of BCL2, resulting in a worse outcome than mild hypothermia.

Retinoid-enhanced gap junctional communication is achieved by increased levels of connexin 43 mRNA and protein.

Natural and synthetic retinoids are potent inhibitors of experimental carcinogenesis in animals and cause reversion of premalignant lesions in humans. In the model C3H 10T1/2 cell system, retinoids enhance postconfluent growth control, reversibly inhibit carcinogen-induced transformation, and enhance gap junctional intercellular communication. These effects are highly correlated. 10T1/2 cells were found to express low levels of connexin 43, a gap junctional protein first found in the heart. After treatment of confluent 10T1/2 cells with the synthetic retinoid tetrahydrotetramethylnapthalenylpropenylbenzoic acid (TTNPB), levels of connexin 43 mRNA and protein increased within 6 h of treatment, while elevation of junctional communication was detected within 12-18 h. The maximally effective concentration of TTNPB (10(-8) M) caused an approximate 10-fold elevation of connexin 43 gene transcripts after 72 h. Indirect immunofluorescence microscopy using a polyclonal antibody to the synthetic C-terminal region of connexin 43 demonstrated that TTNPB induced many fluorescent plaques in regions of cell-cell contact. These results provide a molecular basis for the retinoid-enhanced junctional communication in 10T1/2 cells. It is proposed that one action of retinoids is to modulate the intercellular transfer of signal molecules. These could mediate many of the physiological actions of retinoids on growth control and carcinogenesis.