ERS Mediated by GRP-78/PERK/CHOP Signaling Is Involved in Fluoride-Induced Ameloblast Apoptosis.

Fluoride can be widely ingested from the environment, and its excessive intake could result in adverse effects. Dental fluorosis is an early sign of fluoride toxicity which can cause esthetic and functional problems. Though apoptosis in ameloblasts is one of the potential mechanisms, the specific signal cascade is in-conclusive. High-throughput sequencing and molecular biological techniques were used in this study to explore the underlying pathogenesis of dental fluorosis, for its prevention and treatment. A fluorosis cell model was established. Viability and apoptosis rate of mouse ameloblast-derived cell line (LS8 cells) was measured using cell counting kit-8 (CCK-8) assay and flow cytometry analysis. Cells were harvested with or without 2-mM sodium fluoride (NaF) stimulation for high-throughput sequencing. Based on the sequencing data, subcellular structures, endoplasmic reticulum stress (ERS), and apoptosis related biomarkers were verified using transmission electron microscopy, quantitative real-time polymerase chain reaction, and Western blotting techniques. Expression of ERS markers, apoptosis related proteins, and enamel formation enzymes were detected using Western blotting after addition of 4-phenylbutyrate (4-PBA). NaF-inhibited LS8 cells displayed time- and dose- dependent viability. Additionally, apoptosis and morphological changes were observed. RNA-sequencing data showed that protein processing in endoplasmic reticulum was obviously affected. ERS and apoptosis were induced by excessive NaF. Downregulation of kallikrein-related peptidase 4 (KLK4) was also observed. Inhibition of ERS by 4-PBA rescued the apoptotic and functional protein changes in cells. Excessive fluoride induces apoptosis by activating ERS, which is mediated by GRP-78/PERK/CHOP signaling. Key proteinase is present in maturation-stage enamel; KLK4 was also affected by fluoride, but rescued by 4-PBA. This study presents a possibility for therapeutic strategies for dental fluorosis, while further exploration is required.

Factors analysis on success rate of endovascular recanalization for non-acute long segmental internal carotid artery occlusion / 中华放射学杂志

Objective:To investigate the risk factors related to successful endovascular recanalization for non-acute long segmental occlusion of internal carotid artery and propose a strategy for selecting proper candidates for such procedure.Methods:From January 2018 to October 2022, 120 consecutive patients with non-acute long segmental internal carotid artery occlusion received the first intended endovascular recanalization treatment in the First Affiliated Hospital of Zhengzhou University. Potential variables including epidemiology, symptomatology, angiographic morphology and interventional techniques were retrospectively analyzed. Univariate and multivariate logistic regression analyses were made to investigate the independent risk factors for successful recanalization. Four types were divided according to the existence of tapered stump and ophthalmic artery flow reversion based on DSA images: A: tapered stump (-), ophthalmic artery flow reversion (-); B: tapered stump (-), ophthalmic artery flow reversion (+); C: tapered stump (+), ophthalmic artery reversion (-); D: tapered stump (+), ophthalmic artery (+). Investigation of the relationship between procedure success rate and group dividing was performed.Results:Totally 120 patients were all included. The technical success rate was 75.83% (91/120). The periprocedural complication rate was 9.17% (11/120), including 4 (3.33%) intracranial hemorrhagic events, 1 (0.83%) ischemic stroke event, 1 (0.83%) microcatheter perforation, 3 (2.75%) cavernous carotid fistulas, 2 (1.67%) iatrogenic dissections. None of these complications led to severe neurological damage or death. Through multivariate logistic regression, tapered stump (OR=4.10, 95%CI 1.19-14.16), retrograde filling of ophthalmic artery (OR=3.16, 95%CI 1.13-8.88), only cervical segment occlusion of internal carotid artery (OR=10.78, 95%CI 2.08-55.74) were the independent risk factors associated with higher technical success rate. All cases were divided into A-D four types considering the tapered stump and reversed ophthalmic flow existing or not. Technical success rates in A-D types were 30.00% (3/10), 66.67% (8/12), 70.00% (28/40), 89.66% (52/58) respectively, and the complication rates of the four types were 10.00% (1/10), 8.33% (1/12), 17.50% (7/40), 3.45% (2/58). Multivariate logistic regression showed group pattern was the independent factor on technical success rate (OR=3.72, 95%CI 1.42-9.77).Conclusions:Tapered stump, reversed ophthalmic artery flow and pure extracranial artery occlusion are the independent factors for technical success rate. Group pattern which covered the tapered stump and reversed ophthalmic artery flow is also related to technical success rate. However, the results need further confirmation with the prospective trial and a larger sample.

Mechanism of vascular endothelial cells ferroptosis in cervical spondylosis of vertebral artery type / 中国临床药理学与治疗学

Ferroptosis is a novel type of cell death, characterized by iron overload and lipid metabolism disorders, and is closely related to the occurrence of cardiovascular and cerebrovascular diseases, tumors, and acute injuries. When tissues and organs of the body are in a state of ischemia and hypoxia, iron ions initiate lipid peroxidation and produce a large number of oxygen free radicals. A series of oxidative stress reactions are more likely to trigger ferroptosis. In the process of cervical spondylosis of vertebral artery type, insufficient blood supply to the vertebral artery caused by degenerative changes of the cervical spine leads to imbalance of iron homeostasis and abnormal amino acid metabolism. Then ferroptosis is induced and plays an important role in the development of cervical spondylosis of vertebral artery type. This paper reviewed the mechanism of ferroptosis in the occurrence of cervical spondylosis of vertebral artery type, in order to provide new ideas and perspectives for the study of related problems of the disease.

Research on the construction and application of postgraduate teaching case base of rotation in department of cardiology / 中华医学教育探索杂志

Objective:To construct the postgraduate teaching case database of rotation in department of cardiology, and to explore its application effect.Methods:The postgraduate teaching case base of rotation in department of cardiology was constructed during April 2020 to December 2020. A total of 32 graduate students rotating in Department of Cardiology of Affiliated Hospital of Guilin Medical University from January 2021 to April 2021 were selected and randomly divided into two groups. The routine group adopted the traditional teaching method, and the research group applied the teaching case base on this basis, both for one month. The examination results, the changes of clinical practice ability before and after the teaching, and the satisfaction with the teaching mode were compared between the two groups. SPSS 22.0 was used for t test and chi-square test. Results:The final results of the theoretical examination and practical operation examination of the two groups were higher than those of the entrance examination ( P<0.05), and the results of the theoretical examination and practical operation examination of the research group were higher than those of the routine group ( P<0.05). The scores of clinical practice ability of inquiry, case analysis, diagnosis, treatment and follow-up in the two groups after teaching were higher than those before teaching ( P<0.05), and the scores of clinical practice ability in the research group after teaching were higher than those in the routine group ( P<0.05). The satisfaction scores on improving examination results, enhancing clinical practice ability, deepening professional understanding and enhancing professional confidence of the teaching mode of the research group were higher than those of the routine group ( P<0.05). Conclusion:The construction and application of postgraduate teaching case base of cardiology rotation can improve the examination results, enhance the clinical practice ability, and achieve the satisfaction of postgraduates.

Exposure level and health risk assessment of chlorination disinfectant by-products in drinking water in Xiangyang City / 公共卫生与预防医学

Objective To understand the exposure level of disinfection by-products (DBPs) in drinking water in Xiangyang City and to evaluate the health risks of the population, so as to provide reference for the safety risk control of drinking water. Methods Sampling and laboratory testing were conducted according to national standard methods. The risk assessment model provided by USEPA was used to evaluate the health risks. Results Trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and tribromomethane (TBM) were detected in drinking water in Xiangyang City. The contents of halogenated hydrocarbon DBPs in water disinfected with liquid chlorine were higher than those with chlorine dioxide. The contents of three DBPs were higher in wet season than those in dry season except TBM. The content of TCM in pipe network terminal water and secondary water supply disinfected with chlorine dioxide was higher than that in factory water. The carcinogenic risk of DBPs in drinking water disinfected with liquid chlorine was 4.33×10-5, and the non-carcinogenic risk was 0.114. The carcinogenic risk of DBPs in drinking water disinfected with chlorine dioxide was 1.24×10-6, and the non-carcinogenic risk was 3.15×10-3. Conclusion The health risk of DBPs in drinking water in Xiangyang City is acceptable, but TCM produced by liquid chlorine disinfection should be paid more attention. It is recommended that chlorine dioxide disinfection be used to reduce the health risks of halogenated hydrocarbon DBPs.

Expression of Sprouty1, 2 and 4 in skin lesions of patients with psoriasis vulgaris and its significance / 中华皮肤科杂志

Objective:To determine the expression of Sprouty in skin lesions of patients with psoriasis vulgaris, and to investigate its correlation with the severity of psoriasis.Methods:From May 2018 to November 2018, 15 lesional skin samples and 10 normal skin samples were collected from patients with psoriasis vulgaris and healthy controls respectively in Dermatology Hospital of Southern Medical University. Immunohistochemical study was performed to determine the distribution of Sprouty1, 2 and 4 proteins in psoriatic lesions and normal skin tissues, Western blot analysis to determine the protein expression of Sprouty1, 2 and 4, reverse transcription (RT) -PCR to measure the mRNA expression of Sprouty1, 2 and 4. Pearson correlation analysis was used to analyze the correlation between Sprouty protein expression and psoriasis area and severity index (PASI) scores.Results:Immunohistochemical study showed that Sprouty1, 2 and 4 were all expressed in psoriatic lesions and normal skin tissues. Sprouty1 was strongly expressed in the cell membrane and cytoplasm of granular layer cells in the control group, but slightly expressed in the cell membrane of granular layer cells in the psoriasis group. Sprouty4 was more strongly expressed in the psoriasis group than in the control group, and Sprouty2 was slightly expressed in both the 2 groups. RT-PCR and Western blot analysis showed that Sprouty1 mRNA and protein were both expressed in the psoriasis group and control group, and significantly lower in the psoriasis group (0.844 ± 0.169, 0.148 ± 0.141 respectively) than in the control group (0.972 ± 0.105, 0.413 ± 0.108 respectively, both P < 0.05) ; the Sprouty1 protein expression was negatively correlated with the PASI score in the psoriasis group ( r = -0.628, P = 0.012) . The psoriasis group showed significantly increased protein and mRNA expression of Sprouty4 (1.306 ± 0.283, 1.727 ± 1.017 respectively) compared with the control group (0.584 ± 0.304, 0.714 ± 0.615, t = 6.063, 2.814, respectively, both P < 0.05) , and the Sprouty4 protein expression was positively correlated with the PASI score in the psoriasis group ( r = 0.812, P < 0.001) . The Sprouty2 protein and mRNA were slightly expressed in the 2 groups, and no significant difference was observed between the 2 groups (both P > 0.05) ; there was no significant correlation between the Sprouty2 protein expression and PASI score ( r = 0.436, P = 0.104) . Conclusion:The protein expression of Sprouty1 and 4 in the psoriatic lesions is correlated with the PASI score, suggesting that Sprouty1 and 4 are related to the occurrence of psoriasis.

Expression of Myocardial Levels of Connexin 43, 40 in Experimental Dog Model of Sympathomimetic Atrial Fibrillation / 中国循环杂志

Objective: To explore the expression of myocardial levels of connexin 43(Cx43), Cx40 in experimental dog model of sympathomimetic atrial fibrillation (AF). Methods: 15 mongrels dogs were randomly divided into 3 groups: Control group, Rapid atrium pacing (RAP) group and RAP+isoprenaline (ISO) perfusion group. n=5 in each group. The hearts were taken to establish in vitro langendorff cardiac perfusion model. Atrial effective refractory period (AERP) and AF inducing rate were tested;intracellular expression and distribution of nerve growth factor (NGF) and tyrosine hydroxylase (TH) were examined by immunohistochemistry, total protein contents of Cx43 and Cx40 were measured by Western blot analysis, mitochondria morphology was observed by transmission electron microscope and mitochondria reactive oxygen species (ROS) generation was detected by fluorescent colorimetric method. Results: AERP was similar between Control group and RAP group (166±5.1) ms vs (160±3.2) ms which cannot induce AF; while it was shortened in RAP+ISO group (148±3.7) ms, P<0.05 which may successfully induce AF.Compared with Control group, mitochondria was slightly swollen in RAP group and the matrix was intact, while mitochondria was obviously swollen in RAP+ISO group and part of matrix was transparent; total protein contents of Cx43 and Cx40 were lower in both RAP group and RAP+ISO group, P<0.05; in addition, they were even lower in RAP+ISO group than RAP group, P<0.05. Compared with Control group and RAP group, RAP+ISO group had increased expression and distribution of NGF, TH and mitochondria ROS generation, P<0.05; NGF, TH and ROS in RAP group were higher than Control group, P<0.05. Conclusion: Sympathetic AF has been related to the contents and changes of myocardial levels of CX43 and Cx40; sympathetic nerve might trigger AF by oxidative stress induced down-regulation of myocardial CX43 and Cx40 in experimental dog model.

Effects of sympathomimetic agent on remodeling of connexin 43 in atrium of isolated heart with rapid atrial pacing / 中国病理生理杂志

AIM:To investigate the changes of connexin 43 (Cx43) via establishing a model of sympathomi-metic atrial fibrillation ( AF) .METHODS:The mongrels ( n=15) were randomly divided into control group , rapid atrial pacing (RAP) group and isoprenaline (ISO) perfusion+RAP group (ISO+RAP group).All mongrels’ hearts were taken out rapidly by median sternotomy to establish the cardiac model with Langendorff perfusion in vitro.The atrial effective re-fractory period ( AERP) and AF inducability were tested .The expression and distribution of tyrosine hydroxylase ( TH) were analyzed by immunohistochemistry .Total protein level of Cx 43 and phosphorylation of Cx 43 were determined by West-ern blot.The distribution of Cx43 were also observed by immunofluorescence staining .The cell apoptosis was analyzed by TUNEL staining.The generation of reactive oxygen species ( ROS) in the mitochondria was measured by fluorescence spec-trophotometry .RESULTS:No significant change of AERP was found between control group and RAP group , while that in ISO+RAP group was significantly decreased (P<0.05) and induced AF.Compared with control group, the expression of TH, apoptotic index and the generation of ROS increased gradually (P<0.05), while the content of Cx43 decreased grad-ually both in the total protein and the phosphorylation levels in RAP group and ISO +RAP group (P<0.05).The fluores-cence intensity of Cx43 was also attenuated and Cx43 were lateralized apparently in RAP group , while Cx43 were character-ized as punctate distribution in ISO +RAP group.CONCLUSION:Sympathetic nerves may activate autophagosome at in-tercalated discs and trigger cell apoptosis , resulting in remodeling and downregulation of Cx 43 via oxidative stress , thus having effects on mediating and maintaining AF .

Insights into the Therapeutic Potential of Heparinized Collagen Scaffolds Loading Human Umbilical Cord Mesenchymal Stem Cells and Nerve Growth Factor for the Repair of Recurrent Laryngeal Nerve Injury

Recurrent laryngeal nerve (RLN) injury can result in unilateral or bilateral vocal cords paralysis, thereby causing a series of complications, such as hoarseness and dyspnea. However, the repair of RLN remains a great challenge in current medicine. This study aimed to develop human umbilical mesenchymal stem cells (HuMSCs) and nerve growth factor (NGF)-loaded heparinized collagen scaffolds (HuMSCs/NGF HC-scaffolds) and evaluate their potential in the repair of RLN injury. HuMSCs/NGF HC-scaffolds were prepared through incorporating HuMSCs and NGF into heparinized collagen scaffolds that were prefabricated by freeze-drying in a template. The resulting scaffolds were characterized by FTIR, SEM, porosity, degradation in vitro, NGF release in vitro and bioactivity. A rabbit RLN injury model was constructed to appraise the performance of HuMSCs/NGF HC-scaffolds for nerve injury repair. Electrophysiology, histomorphology and diagnostic proteins expression for treated nerves were checked after application of various scaffolds. The results showed that the composite scaffolds with HuMSCs and NGF were rather helpful for the repair of broken RLN. The RLN treated with HuMSCs/NGF HC-scaffolds for 8 weeks produced a relatively normal electromyogram, and the levels of calcium-binding protein S100, neurofilament and AchE pertinent to nerve were found to be close to the normal ones but higher than those resulted from other scaffolds. Taken together, HuMSCs/NGF HC-scaffolds exhibited a high score on the nerve injury repair and may be valuable for the remedy of RLN injury.

"Research on practical teaching reform of humanities and social science in medical colleges and uni-versities based on post competency - take ""modern Chinese"" course as an example" / 中华医学教育探索杂志

Modern Chinese course in the Third Military Medical University adhered to post com-petency oriented function for curriculum. It simplified, merged and enhanced the traditional Chinese teach-ing content, to help students to establish a standardized use of language awareness, and establish a sense of cultural identity, which helped medical students learn and appreciate literary works from all countries and famous narrative medical text, improved their moral sentiments, and aroused their empathy and empathy for the response. Under the guidance of the basic theory of spoken language, scientific, systematic, strict oral expression skills and effective doctor-patient communication skills training were carried out for medical stu-dents, so as to cultivate medical students' humanistic spirit and the scientific spirit.

Intensity modulated radiation therapy for primary liver cancer with portal vein/inferi-or vena cava tumor thrombosis / 中国肿瘤临床

Objective:To evaluate the clinical outcomes of patients after intensity modulated radiation therapy (IMRT) for hepatocellu-lar carcinoma (HCC) with portal vein tumor thrombosis (PVTT) or inferior vena cava tumor thrombosis (IVTT). Methods:A registry data-base of 41 patients treated with IMRT for HCC with PVTT or IVTT in Radiotherapy Center of No.3 Hospital of Beijing Chinese People Armed Police Forces between January 2013 and May 2015 were analyzed retrospectively. The biological effective dose of radiation was ranged 48-94Gy. Short-term effects and prospective efficacy were observed. Log-rank test, Cox regression were used for survival analysis and prognostic factor identification. Results: Grade 2 or higher level gastrointestinal reaction was observed in 12 patients (29.3%). Hematological toxicity was observed in 11 patients (26.8%), and radiation-induced liver disease was observed in 6 patients (14.6%). We found that 29.3%of patients achieved a complete response and 31.7%of patients achieved a partial response. The stable and progressive disease rates were 39.0%and 0.0%, respectively. Median patient survival was 11 months, and the 1-year survival rate was 34.1%. The significant independent variables associated with the overall survival included Child-Pugh grade, AFP test, and CHE lev-el. Conclusion:IMRT is a safe and effective treatment for PVTT or IVTT in patients with HCC.

[Advances in the research of effects of music therapy on pain and anxiety in burn patients].

Pain and anxiety engender major psychic problems during all phases of treatment for burn patients. Analgesic alone does not allay these problems satisfactorily in these patients. Music therapy, as an important complementary and alternative therapy, has been widely used in multiple medical fields. However, its positive effect on alleviation of pain and anxiety in burn patients is undefined. The objective of this review is to summarize the feasibility, application fields, methods, and the effectiveness of music therapy in allaying pain and anxiety of burn patients during the whole course of treatment.

Three-port transumbilical endoscopic cholecystectomy performed using conventional laparoscopic instruments / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of three-port transumbilical endoscopic cholecystectomy performed using conventional laparoscopic instruments.</p><p><b>METHODS</b>Thirty-two patients undergoing three-port transumbilical endoscopic cholecystectomy using conventional laparoscopic instruments (group A) with 3 ports around the umbilicus were compared with 96 patients (group B) receiving the conventional 4-port routine endoscopic cholecystectomy.</p><p><b>RESULTS</b>All the procedures were successfully completed without conversion to open laparotomy. In group A, the procedures were completed smoothly in 30 cases while 2 cases required another port (5 mm) punctured below the xyphoid due to severe adhesion around the cyst. The median operating time was 39.7∓5.2 min in group A, significantly longer than that in group B (25.3∓3.3 min, P<0.001), but the patients in group A obtained better cosmetic results (P<0.001); the median blood loss, recovery time of postoperative intestine function, length of postoperative hospital stay, and the rate of use of postoperative painkillers were comparable between the two groups. Bile leakage or other postoperative complications occurred in none of cases in the two groups.</p><p><b>CONCLUSION</b>In cases without severe adhesion around the cyst, three-port transumbilical endoscopic cholecystectomy using conventional laparoscopic instruments is a safe and feasible alternative to routine endoscopic cholecystectomy with better cosmetic results.</p>

The nephroprotective effects of prostaglandin E1 in the elderly undergoing coronary angiography or intervention treatment / 中华老年医学杂志

Objective To investigate the nephroprotective effects of prostaglandin E1 (PGE1) in the elderly undergoing coronary angiography or intervention. Methods161 patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) were randomly assigned to PGE1 group (n=87 cases) and control group (n=74 cases).10 μg lipo-PGE1 added to 100 ml normal saline were administered intravenously once daily for 5 days before and 2 days after the operation.The serum levels of creatinine (Scr) and cystatin C (Cys C) were measured on admission and 48 h after the procedure.Results After the procedure,the levels of Scr and Cys C were increased (P＜0.01) and creatinine clearance (Ccr) was decreased (P＜0.05) in control group than in PGE1 group.The incidence of contrast-induced acute kidney injury (CI-AKI) in control group 〔12.2％ (9/74)〕 was higher than in PGE1 group 〔3.4％(3/87)〕 (P＜0.05).The application of P(GE1 decreased CI-AKI,but high basic level of Scr and diabetes mellitus enhanced the incidence of CI-AKI by logistic regression.The serum levels of Cys C had negative correlation with Ccr (r=-0.615,P＜0.01).Conclusions Perioperative application of PGE1 has nephroprotective effects in the elderly undergoing CAG or PCI,and decreases the incidence of CI-AKI.The serum levels of Cys C is one of ideal indexes for auxiliary diagnosis of CI-AKI.

Effects of heptanol preconditioning on structure, function and Cx43 content of mitochondria in rabbit model of myocardial ischemia/reperfusion injury / 中国病理生理杂志

AIM: To investigate the effects of heptanol preconditioning on the changes of structure, function and connexin 43 (Cx43) content in mitochondria in a rabbit model of myocardial isehemia-reperfusion (IR) injury. METHODS: In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 4 h. Sixty-four rabbits were randomly divided into 4 groups (n=16 in each group): sham operation group (sham group), ischemia-reperfusion group (IR group), ischemic preconditioning group (IP group) and heptanol preconditioning group (HT group). All rabbits in the 4 groups were killed 4 h after reperfusion. Myocardial infarct size was determined at the end of the experiment. Mitochondria was isolated by centrifugations. The ultrastructural changes of the mitochondria were observed under electronic microscope. The mitochondrial membrane potential, Ca~(2+) concentration, MDA content and SOD activity of myocardial mitochondria were also examined. The content of mitochondria Cx43 was detected by Western blotting. RESULTS: Compared to IR group, the myocardial infarct size was significantly reduced in IP (18.97%±2.80%) and HT (19.97%±3.80%) groups, the damage of mitoehondrial ultrastructure was milder (P<0.05), mitochondrial membrane potential was significantly higher and Ca~(2+) concentration was much lower (P<0.01) in IP group and HT group. No significant difference of MDA content and SOD activity in myocardial mitochondria between IR group and HT group was found. However, MDA content were much lower and SOD activity was significantly higher in IP group as compared to IR group (P<0.01). Compared to sham group, the mitochondria Cx43 expression was distinctly decreased compared to IR group (P<0.05) and no significant difference was found between IP group and HT group (P>0.05). CONCLUSION: Heptanol preconditioning protects myocardium from ischemia-reperfusion injury. The mechanism may be related to increasing in mitochondrial membrane potential, alleviating Ca~(2+) overload in myocardial mitochondria and attenuating the decrease in mitochondria Cx43 expression induced by isehemia-reperfusion.

Relation between vagus nerves and remodeling of gap junction in superior vena cava myosleeve in dog with atrial fibrillation / 基础医学与临床

Objective To investigate the relationship between cardiac vagus nerves and changes of connexins(Cx)and intracellular gap junction(GJ)distribution pattern in superior vena cava(SVC)myosleeve in dog with atrial fibrillation(AF).Methods Twenty four hybrid dogs were divided into sham operation group(Sham group,n=8),SVC-AO fat pad removed group(RM group,n=8)and SVC-AO fat pad reserved group(RS group,n=8).In RM group and RS group,right atrial pacing was performed at a frequency of 500～650/min for 6 weeks to establish AF model.AF was induced by programmed stimulation or burst stimulation of atrial pacing.The expression and distribution of Cx40 and Cx43 in the SVC myosleeve tissue in three groups were analyzed by immunofluorescence staining.Transmission electron microscopy was used to observe the uhrastructural organization of gap junction(GJ).Results The rate of inducing sustained AF(＞ 15 min)in RS group was significantly higher than that in RM group (P ＜ 0.01).The expression of Cx40 and Cx43 in the SVC myosleeve in sham group and RS group were significantly higher than that in RM group(P ＜ 0.05).Furthermore,the expression of Cx40 and Cx43 in RS group were obviously higher than that in sham group(P ＜0.05).The ratio of end-to-end to side-to-side in RS group was lower than that in Sham group and RM group.Comparing with RM group,the channel of GJ became shorter and wider in RS group(P ＜0.05).Sarcomere was dissolved and mitochondrion showed vacuole degeneration in RS group.Conclusion The remodeling of Cx40 and Gx43 in SVC myosleeve tissue may be mediated by vagus nerves.It is conducive to the maintenance and stability of AF.However,this effect can be weakened by removing SVC-AO fat pad of canine.

Ischemic postconditioning attenuates myocardial cell injury by ischemia-reperfusion injury in rabbits / 基础医学与临床

Objective To investigate the effects of ischemic postconditioning on apoptosis, structural and functional changes of mitochondria induced by myocardial isehemia/reperfusion (I/R) injury of rabbits and potential mechanism. Methods Eighty healthy rabbits were divided randomly into five groups: sham operation group ( Group Sham) , ischemic reperfusion group (Group IR) , ischemic preconditioning group (Group IP) , ischemic postconditioning group (Group PC) and 5-HD plus ischemic postconditioning group (Group PC +5-HD). All rabbits in the five groups were killed 4 h after reperfusion. The hearts were quickly collected for microscopy by TUNEL. We observed ultrastructural changes of myocardium under electron microscope and examined mitochondrial membrane potential and Ca~(2+) concentration, MDA content and SOD activity of myocardial mitochondria. Results Compared with group IR, the damage of mitoehondrial ultrastrueture was milder, the apoptosis rate decreased and Ca concentration and MDA content were much lower in group IP and group PC ( P < 0. 05 ). Mitochondrial membrane potential and SOD activity of myocardial mitochondria in group IP and group PC was significantly higher than that in group IR(P<0.05). The protective effect of PC against I/R injury was partially counteracted by 5-HD .Conclusion Ischemic posteonditioning can protect the heart from I/R injury, this is supported by improvement mitochondrial ultrastructure and by decreasing apoptosis, increasing mitochondrial membrane potential and SOD activity, alleviating Ca~(2+) overload and decreasing MDA content in myocardial mitochondria. The cardio protective effects may be explained by mitochondrial ATP sensitive potassium channel.

Transplantation of allogenic mesenchymal stem cells up-regulates connexin 43 expression in rats with myocardial infarction / 基础医学与临床

Objective To investigate the alterations of connexin 43 (Cx43) expression and its distribution at different stages of myocardial infarction (MI) in rats after transplantation of allogenic mesenchymal stem cells (MSCs).Methods Wistar rats were ligated on the left anterior descending coronary artery to make MI models.They were injected with allogenic MSCs,which were induced by 5-aza and labelled by DAPI,during the second operation after 7 days of MI.In subgroups,MSCs were detected by fluorescence microscope.Cx43 expression and GJ distribu-tion were examined by immunohistochemistry after 4,8 or 12 weeks respectively.Results MSCs differentiated into cardiac muscle cell-like cells which were capable of pulsing spontaneously,expressing cTnT and forming myofilament in vitro.Transplanted MSCs can survive in MI host and upregulate Cx43 expression and normalize Cx43 distribution at ischemic zones after 4,8 and 12w.No change of Cx43 was seen at infarcted zones.Conclusion MSCs have the plasticity of differentiating into cardiac muscle cell-like cells which can continuously upregulate Cx43 expression and normalize Cx43 distribution at ischemic zones after 4,8 and 12w.

Establishment of a Rat Model of Myocardial Infarction and the Post-Infarction Changes in Electrophysiology and Left Ventricular Function / 中国实验动物学报

Objective To establish a stable,repeatable and long-lasting rat model of myocardial infarction,and to evaluate the feasibility of monitoring electrophysiological changes and left ventricular function after myocardial infarction by electrocardiography (ECG) and ultrasonic cardiography(UCG). Methods Wistar rats were ligated on the left anterior descending coronary artery after anaesthesia with 10% chloral hydrate and machinery assisted respiration. Then they were monitored by ECG and UCG afer 4,8 and 12 weeks,and were sacrificed and pathologically examined at 12 weeks after operation. Results The rat model of myocardial infarction was established with a survival rate of 83.3% at 72 hours after the operation and 73.3% at 12 weeks after the operation. In the myocardial infarction group,the PR,QRS,QT and QTc intervals were statistically significantly longer than that in the sham operation group. UCG showed that the left ventricular internal diameter at end-diastole (LVIDd) and the left ventricular internal diameter at end-systole (LVIDs) were statiscally significantly higher in the infarction group,and the ejection fraction (EF) and fractional shortening (FS) significantly lower than those in the sham operation group. Long-lasting pathological changes can be seen in the tissues at 12 weeks after operation. Conclusions The method used in the present study is an simple,less injurious and highly successful technique,and the changes in electrophysiology and left ventricular function can be well monitored by ECG and UCG at different times during this period.

Cx43 in mitochondria participates in the protection for heptanol preconditioning on myocardial ischemia/reperfusion injury of rabbits / 中国药理学通报

Aim To investigate the roles of Cx43 in mitochondria and mitochondrial ATP sensitive potassium channe1(mitoK_(ATP)~+)participating in the protection for heptanol preconditioning on myocardial ischemia/reperfusion injury of rabbits.Methods In anesthetized open-chest rabbits,the left anterior descending artery(LAD)was occluded for 30 min and reperfused for 4 hrs.All rabbits were randomly divided into five groups(n=16 in each group):sham operation group(Group Sham),ischemic reperfusion group(Group IR),ischemic preconditioning group(Group IP),heptanol preconditioning group(Group HT)and 5-HD plus heptanol preconditioning group(Group HT+5-HD),All rabbits in the five groups were killed 4h after reperfusion.Myocardial infarct size was determined at the end of the experiment.The heart rate and the mean arterial pressure(MAP)were recorded and plasma CK-MB and cTnI activity were measured at baseline,the end of ischemia,and after 2 hrs and 4 hrs of reperfusion respectively.Mitochondria was isolated with different centrifugations.Ultrastructural changes of mitochondria were observed under electron microscope.The content of the mitochondria Cx43 was detected with Western blot.Results The plasma CK-MB,cTnI activity and myocardial infarct size were significantly reduced in IP(18.97±2.8)% and HT(19.97±3.8)% groups as compared to IR groups (35.67±5.8)%,(P<0.01).Compared to group IR,the damage of mitochondria in group IP and group HT were milder(P<0.01).No significant difference was found between Group IP and Group HT.Compared to sham group, the mitochondria Cx43 expression was distinctly decreased in group IR and group HT+5-HD(P<0.01)and no significant difference was found between Group IP and Group HT.Conclusions Heptanol preconditioning can protect the heart from I/R injury by improving mitochondrial ultrastructure and by attenuating the decrease of mitochondria Cx43 expression induced by I/R.The mitochondrial Cx43 expression may be concerned with depending on mito K_(ATP)~+.