Polymer-based antibiotic sustained-release carrier in treatment of chronic osteomyelitis / 中国组织工程研究

BACKGROUND:In the treatment strategy of chronic osteomyelitis,the local antibiotic slow-release system has attracted much attention in the clinic due to the long-term release of effective concentrations of antibiotics to control the infection,and at the same time,the ability to repair bone defects caused by debridement. OBJECTIVE:To summarize the research status of antibiotic sustained-release carriers prepared from biodegradable polymer-based materials for the treatment of osteomyelitis,and analyze the limitations and challenges. METHODS:Chinese and English key words were"polymer,composite material,osteomyelitis,infectious bone defect,drug delivery systems,antibiotic sustained-release system,3D printing".Relevant articles were searched in PubMed,Web of Science,CNKI,and WanFang databases from January 2015 to August 2023.4 351 articles were obtained in the initial examination,and 87 articles were analyzed after screening. RESULTS AND CONCLUSION:Polymer-based materials have been widely studied in the preparation of antibiotic sustained-release carriers due to their good biocompatibility,biodegradability,thermal stability,and easy processing.However,the antibiotic slow-release carrier composed of a single polymer material cannot meet the standard of infectious bone defect repair materials due to the lack of biomechanical properties.The organic-inorganic composite material carrier,which simulates the formation of natural bone tissue structure,is expected to meet this standard.3D printing technology can precisely control the size,geometry,and spatial distribution of the interconnecting pores of the carrier,and can load the effective concentration of antibiotics to achieve controlled release.The polymer material is the most suitable for 3D printing because of its good thermal stability and plasticity.Therefore,the author believes that on the basis of new biodegradable organic-inorganic composite materials and combined with 3D printing technology,the material-structure-function integrated composite antibiotic slow-release carrier to simulate the extracellular matrix microenvironment is expected to become a novel research direction in the treatment of chronic osteomyelitis.

Comparison of three kinds of palmar approach plate implantation for treatment of unstable distal radius fractures / 中国组织工程研究

BACKGROUND:In the past,it was necessary to cut off the pronator quadratus muscle in the treatment of distal radius fractures.Failure to repair the pronator quadratus muscle can lead to a series of complications. OBJECTIVE:To explore the clinical efficacy of different methods of preserving the pronator quadratus muscle combined with a palmar steel plate in the treatment of distal radius fractures. METHODS:Clinical data of 66 patients with distal radius fractures were retrospectively included,divided into the traditional Henry approach group(group A),the split brachioradialis tendon approach group(group B),and the posterior pronator quadratus muscle approach group(group C),with 22 patients in each group.Postoperative internal fixation,fracture healing,and postoperative complications were observed in the three groups.The visual analog scale score of postoperative wrist pain and forearm rotation angle were compared among the three groups.The Dienst Joint Scale was used to evaluate the wrist function of patients. RESULTS AND CONCLUSION:(1)The surgical time,intraoperative blood loss,and fracture healing time of groups B and C were significantly lower than those of group A(P<0.01).There was no significant difference in intraoperative blood loss and fracture healing time between groups B and C,but the surgical time was shorter in group B.(2)The anteroposterior and lateral wrist X-ray examination 3 days and 1 and 3 months after surgery exhibited that there were no significant differences in radial height,palm angle,and ulnar deviation angle among the three groups(P>0.05).No significant difference was detected in various indicators during the same phase among the three groups(P>0.05).(3)At a follow-up of 12 months after surgery,there were no significant differences in visual analog scale scores and forearm rotation angle among the three groups.However,the evaluation results at 1 and 3 months after surgery demonstrated significant differences in visual analog scale scores and forearm rotation angle among the three groups(P<0.05).Among them,group C had a lower visual analog scale score and a larger forearm rotation angle.(4)According to the Dienst joint scoring standard,the excellent and good rate of wrist joint function evaluation was 86%(19/22),91%(20/22),and 95%(21/22)in groups A,B,and C,respectively 12 months after surgery.(5)All patients did not experience any postoperative vascular or neurological damage or surgical site infection.Group A had three cases of tendon irritation,two cases of traumatic arthritis,and two cases of carpal tunnel syndrome.In group B,tendon irritation occurred in 1 case and joint stiffness in 1 case.There was 1 case of traumatic arthritis and 1 case of carpal tunnel syndrome in group C.(6)It is suggested that different surgical methods for treating distal radius fractures have achieved good clinical results.Placing a steel plate under the pronator muscle can alleviate early postoperative pain,promote early activity,and restore normal life.The brachioradialis tendon approach has more advantages in exposing intraoperative fractures and can shorten the surgical time.

Clinical comparative analysis of computer navigation-assisted versus freehanded pedicle screw placement in lumbar spondylolysis surgery / 中华创伤骨科杂志

Objective:To compare the efficacy of pedicle screw placement between computer navigation guidance and freehand assistance in the surgical treatment of isthmic spondylolysis at the lumbar vertebrae.Methods:A retrospective study was conducted to analyze the 47 patients with bilateral isthmic spondylolysis at the L 5 vertebra who had been treated at Department of Spinal Surgery, The General Hospital of Xinjiang Military Command from January 2020 to April 2023. All were male patients with an age of (24.0±4.3) years. They were divided into a study group (13 cases subjected to pedicle screw placement assisted by computer navigation guidance) and a control group (34 cases subjected to pedicle screw placement assisted freehandedly). The 2 groups were compared in terms of surgical incision length, intraoperative bleeding, screw placement time, postoperative hospital stay, total hospitalization cost, postoperative complications, rate of screw reposition, angle between pedicle screw and upper endplate, angle between bilateral pedicle screws, and placement accuracy; the visual analogue scale (VAS) for pain, Japanese Orthopaedic Association (JOA) score for lumbar spine function, and Oswestry disability index (ODI) were also compared between preoperation, 1-week postoperation, and the last follow-up. Patient satisfaction was assessed according to the modified MacNab criteria, and internal fixation failure and isthmic healing were also evaluated at the last follow-up. Results:There were no statistically significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The differences were not statistically significant in surgical incision length, intraoperative bleeding, screw placement time, postoperative hospital stay, or postoperative complications ( P>0.05). However, in the study group, the total hospitalization cost was significantly higher than that in the control group, the rate of screw reposition [7.7% (2/26)] significantly lower than that in the study group [26.5% (18/68)], the angle between pedicle screw and upper endplate and the angle between bilateral pedicle screws were both significantly smaller than those in the control group, and the placement accuracy [92.3% (24/26)] was significantly greater than that [70.6% (48/68)] in the control group (all P<0.05). All patients were followed up for 7.0 (5.0, 14.0) months. Patients in both groups showed significant improvements in VAS, JOA score, and ODI at postoperative 1 week and the last follow-up compared with the preoperative values, and the improvements at the last follow-up were significantly larger than those at postoperative 1 week ( P<0.05). According to the modified MacNab criteria at the last follow-up, patient satisfaction was rated as excellent in 10 cases, as good in 2 cases and as moderate in 1 case in the study group while as excellent in 27 cases, as good in 3 cases, as moderate in 3 cases and as poor in 1 case in the control group. In the study group, there were 1 case of internal fixation failure, 1 case of spine cutting-out by titanium cable, and 12 cases of bony healing of the isthmus; in the control group, there were 2 cases of internal fixation failure, 2 cases of spine cutting-out by titanium cable, and 29 cases of bony healing of the isthmus. Conclusions:In the surgical treatment of bilateral isthmic spondylolysis at the L 5 vertebra, computer navigation-guided pedicle screw placement is safe and reliable, showing an advantage of higher accuracy over freehand placement. It deserves clinical promotion due to its satisfactory therapeutic effects.

Single center experience of transcatheter aortic valve replacement with a simplified operative protocol / 中华心血管病杂志

Objective: To summarize the single center experience of transcatheter aortic valve replacement (TAVR) with a simplified operative protocol. Methods: Consecutive patients who underwent transfemoral TAVR (TF-TAVR) from July 2020 to December 2020 in Fuwai Hospital were retrospectively analyzed. We compared the baseline characteristic, procedure information, 30-day follow-up outcomes of the patients who underwent TF-TAVR without the simplified operative protocol (routine group) or with the simplified operative protocol (simplified protocol group). Results: 93 patients were collected, 42 patients belonging to routine group, 51 patients belonging to simplified protocol group. In simplified protocol group, there were 51 patients planned to use ultrasound-guided femoral access puncture, procedure was successful in all 51 patients (100%). There were 49 patients planned to use the radial artery as the secondary access, procedure was successful in 45 patients (92%). There were 48 patients planned to use the strategy of avoidance of urinary catheter, this strategy was achieved in 35 patients (73%). There were 12 patients planned to use the left ventricular guidewire to pace, procedure was successful in 11 patients (92%). There were no differences in baseline characteristics, major clinical endpoints and 30-day follow-up outcomes between the two groups. Meanwhile, the procedure time ((62.5±17.9)min vs. (78.3±16.7)min, P<0.001), operation room time ((133.7±25.1)min vs. (159.2±42.6)min, P<0.001), X-ray exposure time ((17.2±6.5)min vs. (20.2±7.7)min, P=0.027) were significantly shorten in simplified protocol group compared with the routine group. Conclusion: Our study results indicate that the simplified operative protocol of TF-TAVR is as effective and safe as the routine operative protocol, meanwhile using the simplified operative protocol can significantly increase the operative efficiency of TF-TAVR.

Feasibility of single-stage stent implantation following rotational atherectomy combined with TAVR / 中华心血管病杂志

Objective: To explore the feasibility of the single-stage stent implantation following rotational atherectomy combined with transcatheter aortic valve replacement (TAVR) in treating patients with severe aortic stenosis(AS) and severe calcified coronary artery stenosis. Methods: Three patients who received single-stage stent implantation following rotational atherectomy combined with TAVR in Fuwai hospital from April to October 2019 were included in this retrospective analysis. Clinical and anatomical features (including echocardiography and aortic CT) of the patients were collected, efficacy and safety of this operation strategy were observed and 6 months follow up results were summarized. Results: Three patients (2 females, 66-80 years old) were included. The mean Society of Thoracic Surgeons (STS) risk score was 7.8%. The mean maximum velocity of aortic valve was 4.4 m/s, the mean transvalvular pressure gradient was 53.2 mmHg (1 mmHg=0.133 kPa), mean left ventricular ejection fraction (LVEF) was 48.6%. All three patients had severe calcified coronary artery stenosis: left anterior descending artery (LAD, n=2) and left main coronary artery (LM, n=1), requiring rotary grinding. The mean SYNTAX score was 20. All the procedures were performed through transfemoral access. After aortic valve crossing, all coronary lesions were successfully treated with stent implantation following rotational atherectomy, transfemoral TAVR was then immediately performed with a self-expandable Venus-A valve. One patient underwent"valve-in-valve"implantation due to the high-implantation position of the first valve. The procedures were completed without complications in all the three patients. The immediate effect was satisfactory. Echocardiography results showed that the mean maximum velocity of aortic valve was 2.1 m/s, mean gradient was 9.3 mmHg, and mean LVEF was 59% after the procedure. There was no death and revascularization during the 6 months follow-up. Conclusion: In patients with severe calcified coronary artery and severe AS with high risk of cardiac surgery, the single-stage stent implantation following rotational atherectomy combined with TAVR is feasible and results are satisfactory in this patient cohort.

Left ventricular guidewire pacing during transcatheter aortic valve replacement / 中华心血管病杂志

Objective: To investigate the safety and efficacy of left ventricular guidewire pacing during transcatheter aortic valve replacement (TAVR). Methods: This is a retrospective study. Thirteen patients, who underwent TAVR with left ventricular guidewire pacing from October 2019 to December 2019 in Fuwai Hospital, were included. Clinical data and operational procedure data of the patients were collected. Changes in blood pressure and electrocardiogram were observed during operations. Ascending aorta angiography was performed to evaluate the regurgitation of aortic valve after valve implantion. The incidence of major adverse cardiac events during hospitalization and at 3-months after discharge was recorded. Results: There were 7 male and 6 female patients in this cohort,and age was (73.8±8.3) years old. Among the 13 patients, 9 were tricuspid aortic valves, 3 were bicuspid aortic valves, and 1 was degenerated bioprosthetic surgical aortic valve. TAVR were successfully performed in all of the 13 cases using pacing through the left ventricular guidewire. During balloon dilation, the blood pressure decreased to below 60 mmHg (1 mmHg=0.133 kPa) after 180 beats/min pacing, and the valve release process was smooth and the position was stable. The results of aortography showed that there was no regurgitation in 7 cases, mild regurgitation in 5 cases and moderate regurgitation in 1 case. Three patients required temporary pacing during the procedure due to complete heart block, among whom 1 patient was implanted with permanent pacemaker during hospitalization, and the other 2 patients recovered within 24 hours after operation. In another case, there was no significant change of electrocardiogram during the operation, and complete heart block occurred 10 days after the operation, and treated with permanent pacemaker. The other 10 patients began to carry out bedside activities and rehabilitation training 24 hours after operation. There was no death, myocardial infarction, stroke and other major adverse cardiac events during hospitalization and at 3-month follow-up after discharge. Conclusion: Left ventricular guidewire pacing is a safe and effective strategy for TAVR.

Composite scaffolds for bone tissue engineering: application review and future direction / 中国组织工程研究

BACKGROUND:In general, a single-type artificial bone is difficult to meet the requirements for bone defect repair and extracellular matrix of bone tissue engineering. Compositing and processing the materials with different properties can form the composite-type artificial bone, which can either ensure the biological activity or effectively improve its mechanical properties.OBJECTIVE: To summarize the present situation of the application of composite-type artificial bone and prospects the development trend. METHODS:The literatures were retrieved from CNKI, ScienceDirect, PubMed, SpingerLink, El Village, Wiley databases from January 2000 to April 2017. The key words were "composite scaffold, tissue engineering, artificial bone" in Chinese and English, respectively. The selected literatures were analyzed according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: The requirements for the scaffolds used for bone tissue engineering are complex and it should carefully consider and control various factors used in the design and preparation of scaffolds, including microporous structure, mechanical strength, degradation rate, porosity, growth factor, morphology and surface chemistry, so as to meet the bone tissue engineering applications. The preparation of tissue-engineered bone scaffold is based on biological active substances and matrix materials through a reasonable manner. It simulates the components of natural bone matrix, promotes the adhesion, proliferation and differentiation of bioactive substances, and gives play to its functions of osteogenesis. Although existing techniques and methods have made significant progress in the preparation of composite scaffolds, there is no technique or method to fully meet all the requirements for preparation of tissue-engineered bone scaffold.

An improved method for stem cell derivation from human great saphenous vein / 生物工程学报

The objectiue was to explore how to improve stem cell derivation from human great saphenous vein. After the saphenous vein was cut into small pieces, the cells of the vessel wall were obtained by tissue adherent method and digestion with type Ⅱ collagenase. The morphological changes of blood vessel wall were observed under inverted microscope. The survival of vascular wall cells was assessed by trypan blue staining. Stem cells doubly positive for CD34 and CD117 were sorted out by immunofluorescent staining and flow cytometry. The cells obtained by tissue adherence method exhibited signs of fibrotic changes and aging at the third passage (P3), while the cells extracted by enzymatic digestion still showed colony-like growth. Survival rates of these two groups of cells were (91.7±1.2)% and (97.2±0.7)%, (P=0.005). The results of flow cytometry showed that the positive rates of CD34 and CD117 double positive cells in these two groups were (0.16± 0.05)% and (0.44±0.07)%, respectively, with statistical significance (P=0.005). Immunofluorescent staining showed that the positive rates of double positive stem cells in the two groups were (89.41±2.06)% and (94.03±1.83)%, P<0.05 one week after the sorted stem cells were cultured. The positive rates of CD31, VEGF2 and SMA in the stem cells determined by flow cytometry were (0.12±0.01)%, (0.19±0.02)% and (0.45±0.01)%, respectively, which were not statistically different from those of the control groups. This could rule out substantial inclusion of mature endothelial cells and smooth muscle cells. Tube forming experiment confirmed that these vascular stem cells had developmental plasticity. More viable and morphologically healthy vascular stem cells can be derived by enzymatic digestion. These cells can be widely used in clinical and basic research.

Application of virtual reality technology in the foot fracture-assisted surgery / 中国组织工程研究

BACKGROUND:The application of virtual reality technology in preoperative simulation can reduce the risk in operation effectively and improve the quality of surgery. Virtual reality technology has very important practical significance in the application of surgery. OBJECTIVE:The reverse engineering and virtual reality technology were used to achieve the preoperative simulation of a case of Pilon fracture. METHODS:The affected bones were reconstructed according to the CT data using the patient’s ankle portion in MIMICS software, and the separated bone fractures were restored. According to the characteristics of virtual reality technology, further processing on bone model was carried out using Geomagic software;the models of the fractured bones were exported with STL format. The restored bone fragments were checked up to determine integrity in the virtual reality operation platform. These models were used to do simulated operations in the virtual reality operation platform. RESULTS AND CONCLUSION:A case of Pilon fracture was simulated by using reverse engineering and virtual reality technology preoperatively. The processed 3D model was introduced into the virtual reality system to simulate the operation and help doctors choose the type, position and direction of the surgical approach and plate;the effect is good.

Optimization analysis on mechanical properties of scaffolds for bone tissue engineering based on finite element method / 医用生物力学

Objective To analyze the influence of microporous parameters on mechanical behavior of bone tissue engineered-scaffolds, and provide references for optimizing the microporous structure design. Methods The finite element models of scaffolds with microporous structures were established by using ANYSYS software. The relationships between porosity and maximum equivalent stress as well as maximum total deformation were calculated. The effects of microporous spacing and diameter on maximum equivalent stress, maximum total deformation and internal strain were compared and analyzed. Results The influence rule of microporous spacing in x and y direction was consistent. With the increase of microporous spacing from 0.6 mm to 2.0 mm, the maximum equivalent stress reduced from 63.1 MPa to 46.3 MPa, the maximum total deformation reduced from 23.8 μm to 21.8 μm, and the proportion of the best strain range increased from 80% to 84%. However, with the increase of microporous spacing in z direction, the maximum equivalent stress increased from 38.3 MPa to 47.8 MPa, the maximum total deformation increased from 20. 8 μm to 22.8 μm, and the proportion of the best strain range fluctuated within the range of 82%-85%. With the increase of microporous diameter in x and y direction from 0.1 mm to 1.0 mm, the maximum equivalent stress increased from 32.4 MPa to 78.4 MPa, the maximum total deformation increased from 19.9 μm to 38.2 μm, and the proportion of the best strain range reduced from 90% to 53%. With the increase of microporous diameter in z direction, the maximum equivalent stress reduced from 58.8 MPa to 37.9 MPa, the maximum total deformation increased from 23.3 μm to 25.9 μm, and the proportion of the best strain range increased from 82% to 87%. Conclusions The greater the porosity and the proportion of the best strain range, the smaller maximum equivalent stress and maximum total deformation would be, the scaffolds would have the better biological and mechanical properties. These results have reference values for design and optimization of scaffold structure.

Clinical research progress of distal tibial fracture in surgical treatment / 中国医学装备

Distal tibial fractures (Distal tibial fracture) is a common clinical fractures type, more for high-energy damage, fracture type is more complicated. Because of the distal tibia special anatomic structure (soft tissue is less, less blood supply), if the operation method is not suitable or fixed equipment selection is not reasonable, because fracture healing, osteomyelitis, also can damage the function of the ankle joint. Treatment shall be based on the fracture position, type, in the process of the polluted situation and surrounding soft tissue trauma injury and so on many factors that determine the way and the internal fixation methods. This paper reviews recent year different types of distal tibial fracture fixation and fixed ways of literature research, in the treatment of distal tibial fracture clinical practice to provide the reference of objective reasonably select fixation and evaluation standard.

Safety and feasibility of carotid artery stenting in patients with coexisting carotid and coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of carotid artery stenting (CAS) for treating patients with coexisting carotid and coronary artery disease.</p><p><b>METHODS</b>The clinical data of 237 consecutive patients [(66.1 ± 7.7) years old, 79.7% male] with coexisting carotid and coronary artery disease undergoing CAS in Fuwai hospital from January 2005 to June 2010. The patients were analyzed retrospectively.Indication for CAS was defined as carotid artery diameter reduction of > 60% (symptomatic) or > 80% (asymptomatic) with suitable carotid artery anatomy for stenting. Thirty-day rates of stroke, death and myocardial infarction after CAS were assessed.</p><p><b>RESULTS</b>All patients suffered from coronary artery disease, of whom 87(36.7%) had unstable angina pectoris and 82(34.6%) had recent myocardial infarction (< 30 days). The procedural success rate of CAS was 99.2 % (235/237). Cerebral protection devices were used in 234 patients (99.6%). Among them, 36(15.2%) patients received simultaneous bilateral CAS and 79(33.3%) patients underwent simultaneous percutaneous intervention of other non-coronary arteries.Within 30 days after CAS, 127(53.6%) patients underwent coronary revascularization, including 118(49.6%) coronary artery bypass grafting and 9 (3.8%) percutaneous coronary intervention. The rate of major stroke, minor stroke, death and myocardial infarction from time of CAS to 30 days was 2.1% (5/237), 3.0% (7/237),0.4% (1/237) and 0.4% (1/237) respectively.</p><p><b>CONCLUSION</b>Data from this study indicate that CAS is safe and feasible for treating patients with coexisting carotid and coronary artery disease with a low incidence of periprocedural complication rate.</p>

Clinical analysis of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the safety and feasibility of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis.</p><p><b>METHODS</b>The clinical data of 39 consecutive patients with bilateral atherosclerotic carotid stenosis undergoing simultaneous bilateral carotid artery stenting in Fuwai hospital from January 2005 to December 2009 were collected and analyzed retrospectively. The reduction of the angiographic diameter stenosis after stenting and clinical outcomes of 30 days after stenting including hyperperfusion syndrome, hemodynamic depression, stroke, myocardial infarction and death were assessed.</p><p><b>RESULTS</b>The patients were 43 - 78 (65.9 ± 8.5) years old, and there were 25 (64.1%) male. Carotid stenting procedure success rate was 100%. Distal embolic protection devices were used in all patients, and 20 (51.3%) out of 39 patients underwent coronary artery bypass surgery after carotid stenting. The angiographic diameter stenosis reduced from (87.0 ± 5.8)% to (10.2 ± 5.6)% after stenting (P < 0.01). Up to 30 days after carotid artery stenting, the incidence of hyperperfusion syndrome, hemodynamic depression, minor stroke, major stroke, myocardial infarction and death was 2.6% (1/39), 28.2% (11/39), 5.1% (2/29), 0, 2.6% (1/39), 2.6% (1/39), respectively.</p><p><b>CONCLUSION</b>The data show that simultaneous bilateral carotid stenting is a technically feasible and safe alternative for patients with severe bilateral atherosclerotic carotid stenosis.</p>

Clinical and angiographic correlates of left ventricular dysfunction in patients with three vessel coronary disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Among patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined.</p><p><b>METHODS</b>Among 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined.</p><p><b>RESULTS</b>Among 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%.</p><p><b>CONCLUSION</b>Among individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.</p>

Readthrough of nonsense mutation W822X in the SCN5A gene can effectively restore expression of cardiac Na+ channels W822X / 中华心血管病杂志

<p><b>OBJECTIVE</b>In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene.</p><p><b>METHODS</b>The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel.</p><p><b>RESULTS</b>In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins.</p><p><b>CONCLUSION</b>Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.</p>

The Val606Met mutation of human beta myosin heavy chain in a Chinese familial hypertrophic cardiomyopathy family / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the disease-causing gene mutation in Chinese families with hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>Samples of peripheral blood were collected from three Chinese families with HCM (at least two HCM patients existed/family). The exons in the functional regions of the beta myosin heavy chain gene (MYH7) were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>A Val606Met missen mutation was identified in the exon 16 of MYH7 gene in a Chinese family and this mutation was identified in all HCM patients (n = 4) and there was also a 15-years-old young mutation carrier who was not HCM patient now (penetrance of 80%). This mutation was not identified in other healthy family members in this family, in other 2 Chinese familiar HCM families and in 120 non-HCM control patients.</p><p><b>CONCLUSION</b>The Val606Met missen mutation is closely associated with familiar HCM in a Chinese family which is associated with clinical phenotype with a penetrance of 80%.</p>

Telomere,telomerase,cell of immortalization and aging / 国际生物医学工程杂志

Normal cells have limited proliferation ability.After certain cycles of proliferation,they will lose the response ability to growth factors and finally cease division and start the course of aging. In current opinion,lacking of the terminal end of a chromosome(telomere)is the cause for cells to loss the proliferation ability and leads cells to aging and death.The human telomerase catalytic subunit 1(hTERT)can activate telomemse which prolong DNAs of the terminal end of chmmosome and help cells gain genomic stabilization.The discoveries of telomere,telomerase and hTERT provide new idea for studying of cell aging and the findings are also applied in the establishment of immortal cell line. Also they may play an important role in the studv of biological feature of seed cell in tissue engineering and the establishment of cell bank.

Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial fibrillation is a common arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (G/T) at position 1057 in the KCNE4 gene, resulting in a glutamic acid (Glu, E)/aspartic acid (Asp, D) substitution at position 145 of the KCNE4 peptide, was found in our laboratory to be associated with idiopathic atrial fibrillation (atrial fibrillation more frequent with KCNE4 145D). However, the functional effect of the KCNE4 145E/D polymorphism is still unknown.</p><p><b>METHODS</b>We constructed KCNE4 (145E/D) expression plasmids and transiently co-transfected them with the KCNQ1 gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possible functional consequences of the single nucleotide polymorphism. Quantitative data were analyzed by Student;s t test. Probability values less than 0.05 were considered statistically significant.</p><p><b>RESULTS</b>A slowly activating, non-inactivating voltage-dependent current ((24.0 +/- 2.9) pA/pF, at +60 mV)) could be recorded in the cells transfected with KCNQ1 alone. Co-expression of wild type KCNE4 inhibited the KCNQ1 current ((7.3 +/- 1.1) pA/pF)). By contrast, co-expression of KCNE4 (145D) augment the KCNQ1 current ((42.9 +/- 7) pA/pF)). The V(1/2) of activation for the KCNQ1/KCNE4 (145D) current was shifted significantly towards the depolarizing potential compared to that for the KCNQ1 current ((-2.3 +/- 0.2) mv vs (-13.0 +/- 1.5) mv, P < 0.01)) without changing the slope factorkappa. Furthermore, KCNE4 (145D) also affected the activation and deactivation kinetics of KCNQ1 channels.</p><p><b>CONCLUSION</b>We provide experimental evidence that the KCNE4 (145E/D) polymorphism exerts the effect of "gain of function" on the KCNQ1 channel. It may underlie the genetic mechanism of atrial fibrillation. Further studies on the functional association between I(Ks) and KCNE4 (145D) polymorphism in cardiac myocytes are suggested.</p>

Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province.</p><p><b>METHOD</b>The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women].</p><p><b>RESULTS</b>The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern.</p><p><b>CONCLUSION</b>The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.</p>

Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S / 中华心血管病杂志

<p><b>OBJECTIVE</b>To identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro.</p><p><b>METHODS</b>Mutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system.</p><p><b>RESULTS</b>Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT.</p><p><b>CONCLUSION</b>Present study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.</p>