Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells / 药学学报

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Point electro-cauterization versus holmium laser cauterization in the treatment of post-ejaculation hematuria / 中华男科学杂志

Objective@#To investigate the advantages and disadvantages of point electro-cauterization (PEC) and holmium laser cauterization (HLC) in the treatment of post-ejaculation hematuria.@*METHODS@#From January 2015 to December 2018, 73 patients with post-ejaculation hematuria, aged 24－63 (36.8 ± 4.2) years, underwent PEC (n = 35) or HLC (n = 38) after failure to respond to 3 months of conservative treatment. We compared the hospital days, total hospitalization expenses, maximum urinary flow rate (Qmax), average urinary flow rate (Qavg), Hamilton Anxiety Rating Scale (HAMA) score, postoperative duration of hematuria, and recurrence rate at 3 and 6 months after surgery.@*RESULTS@#All the patients experienced first ejaculation but no post-ejaculation hematuria at 1 month after operation. The recurrence rates were lower in the PEC than in the HLC group at 3 months (5.71% vs 2.63%, P > 0.05) and 6 months postoperatively (8.57% vs 5.26%, P > 0.05). Compared with the baseline, the Qmax was decreased from (18.56 ± 2.53) ml/s to (13.68 ± 3.31) ml/s (P < 0.05) and the Qavg from (14.35 ± 2.26) ml/s to (9.69±1.84) ml/s in the PEC group at 1 month after surgery (P < 0.01), but neither showed any statistically significant difference in the HLC group. Mild to moderate anxiety was prevalent in the patients preoperatively, particularly in those without job or regular income and those with a long disease course or frequent onset, the severity of which was not correlated with age, education or marital status. The HAMA score was decreased from18.65 ± 4.33 before to 12.35 ± 3.63 after surgery in the PEC group (P < 0.01), and from 16.88 ± 2.11 to 6.87 ± 4.36 in the HLC group (P < 0.01). The mean hospital stay was significantly longer in the former than in the latter group (［5.2 + 1.3］ vs ［3.4 ± 0.5］ d, P < 0.01), while the total cost markedly lower (［6.35 ± 1.20］ vs ［12.72 ± 2.15］ thousand RMB ¥, P < 0.05).@*CONCLUSIONS@#Both PEC and HLC are safe and effective for the treatment of post-ejaculation hematuria, with no significant difference in the recurrence rate at 3 and 6 months after operation, but their long-term effect needs further follow-up studies. PEC may increase the risk of negative outcomes of the postoperative urinary flow rate, while HLC has the advantages of better relieving the patient's anxiety, sooner discharge from hospital and earlier recovery from postoperative hematuria, though with a higher total cost than the former.

Epidemiological and clinical characteristics of 69 cases with imported corona virus disease 2019 / 中华传染病杂志

Objective:To analyze the epidemiological and clinical characteristics of patients with imported corona virus disease 2019 (COVID-19) in Beijing City.Methods:A case-control study was performed to retrospectively analyze 69 cases of imported COVID-19 from abroad and 147 cases of domestic confirmed COVID-19 from China as a control group from January 20 to March 20, 2020 admitted to Beijing Ditan Hospital, Capital Medical University.The epidemiological and clinical characteristics were compared.Statistical analysis were performed by t test, Mann-Whitney U test, chi-square test and Fisher exact test. Results:The main sources of the cases in the import group were from the United Kingdom, Italy, Spain and other European countries, with 44.9%(31/69) of the overseas students entering the country by air. The age of the imported group (27(21, 40) years) was lower than the domestic group (43 (32, 59)years), the difference between the two groups was statistically significant ( U=2 828.500, P<0.01). Compared with the domestic group, the proportion of cases with contact history of confirmed cases in the imported group was lower (30.4%(21/69) vs 68.0%(100/147)), the interval between onset and admission ≤seven days was higher (81.2%(56/69) vs 66.0%(97/147)), the proportion of cases with underlying diseases was lower (21.7%(15/69) vs 44.2%(65/147)). The differences between the two groups were all statistically significant ( χ2=26.935, 5.233 and 10.175, respectively, all P<0.05). The proportion of mild cases in the imported group was higher than that in the domestic group (42.0%(29/69) vs 10.9%(16/147)). Seventeen cases with olfactory abnormality and 12 cases with taste abnormality were found in the imported group, while no olfactory and taste abnormality was found in the domestic group. The proportions of fever, weakness, muscle soreness and dyspnea were all lower than those of the domestic group, the differences between the two groups were all statistically significant ( χ2=13.851, 8.118, 9.730 and 16.255, respectively, all P<0.01). The proportions of cases with decreased lymphocyte absolute numbers (37.7%(26/69) vs 67.3%(99/147)) and increased C reactive protein level (15.9%(11/69) vs 51.8%(72/139)) were both lower than the domestic group, and the differences between the two groups were both statistically significant ( χ2=18.015 and 24.722, respectively, both P<0.01). The proportions of cases with ground glass shadow and consolidation of chest computed tomography were lower than those of the domestic group and the differences between the two groups were all statistically significant ( χ2=11.961 and 5.099, respectively, all P<0.05). In terms of complications, the proportions of cases with acute respiratory distress syndrome and acute myocardial injury were lower (2.9%(2/69) vs 10.9%(16/147) and 4.3%(3/69) vs 14.0%(16/114), respectively), and there were statistically significant differences between the two groups ( χ2=4.017 and 4.335, respectively, both P<0.05). There were no cases received mechanical ventilation and extracorporeal membrane oxygenation in the imported group, and the proportions of patients received oxygen therapy and antibiotic treatment were significantly lower than those in the domestic group (13.0%(9/69) vs 26.5%(39/147) and 13.0%(9/69) vs 39.5%(58/147), respectively) and the differences between the two groups were statistically significant ( χ2=4.942 and 15.797, respectively, both P<0.05). Conclusions:The majority of imported COVID-19 cases are mainly from European countries, mostly young and middle-aged, and mostly mild and ordinary types.The symptoms of olfactory and taste abnormality are found for the first time.

Molecular Mechanisms of Increased Heart Rate in Shenxianshengmai-treated Bradycardia Rabbits / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The molecular mechanisms of Shenxianshengmai (SXSM), a traditional Chinese medicine, on bradycardia have been incompletely understood. The study tried to investigate the gene expression profile and proteomics of bradycardia rabbits' hearts after SXSM treatment.</p><p><b>METHODS</b>Twenty-four adult rabbits were randomly assigned in four groups: sham, model, model plus SXSM treatment, and sham plus SXSM treatment groups. Heart rate was recorded in all rabbits. Then, total RNA of atria and proteins of ventricle were isolated and quantified, respectively. Gene expression profiling was conducted by gene expression chip, and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the results of gene expression chip. We used isobaric tags for elative and absolute quantitation and Western blotting to identify altered proteins after SXSM treatment.</p><p><b>RESULTS</b>There was a constant decrease in the mean heart rate (32%, from 238 ± 6 beats/min to 149 ± 12 beats/min) after six weeks in model compared with that in sham group. This effect was partially reversed by 4-week SXSM treatment. Complementary DNA microarray demonstrated that the increased acetylcholinesterase and reduced nicotinic receptor were take responsibility for the increased heart rate. In addition, proteins involved in calcium handling and signaling were affected by SXSM treatment. Real-time RT-PCR verified the results from gene chip. Results from proteomics demonstrated that SXSM enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle in ventricular myocardium to improve ATP generation.</p><p><b>CONCLUSIONS</b>Long-term SXSM stimulates sympathetic transmission by increasing the expression of acetylcholinesterase and reduces the expression of nicotinic receptor to increase heart rate. SXSM also restored the calcium handling genes and altered genes involved in signaling. In addition, SXSM improves the ATP supply of ventricular myocardium by increasing proteins involved in TCA cycle and oxidation-respiratory chain.</p>

Influence of immediate or delayed post space preparation on the apical sealing ability of different root canal sealers / 中国组织工程研究

BACKGROUND: Apical sealing ability is the key to ensure the long-term curative effect of root canal therapy. The post space preparation exposes some inevitable influence on root canal sealing ability, so how to minimize this effect becomes a hot spot.OBJECTIVE: To explore the effects of immediate or delayed post space preparation on the apical sealing ability of different root canal sealers.METHODS: Forty-eight extracted human premolar teeth were obtained, and the tooth crown was cut off. The samples were randomly divided into three groups (n=16 teeth per group). Group A underwent the immediate post space preparation; group B underwent the delayed post space preparation; group C without the post space preparation. Then all groups were subdivided into two groups, and then were filled with the gutta-percha/AH-Plus (groups A1, B1 and C 1)or the gutta-percha/mineral trioxide aggregate (groups A2, B2 and C2). The depth of apical dye penetration was measured using pressure-driven system. RESULTS AND CONCLUSION: There were no significant differences in the apical microleakage between groups A1 and B1, A2 and B2, C1 and C2 (P > 0.05). The apical microleakage in the group A1 was significantly higher than that in the group A2, and the group B1 also showed higher apical microleakage than the group B2 (P < 0.05). Our findings suggest that either immediate or delayed post space preparation exposes little influence on the apical microleakage after root canal filling with gutta-percha/mineral trioxide aggregate, which exhibits better apical sealing ability than the AH-plus.

Expression and clinical significance of HMGA2 in renal carcinoma / 中华肿瘤杂志

Objective@#To detect the high mobility group A2 (HMGA2) expression in renal carcinoma, and to explore the relationship with clinicopathological features and its significance for prognosis.@*Methods@#50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples, and 40 benign renal tumor specimens were used in this study. The expressions of HMGA2 mRNA and protein were detected by RT-PCR, Western blot and immunohistochemical assays, and its relationship with clinicopathological features and prognosis in the renal carcinoma patients was analyzed.@*Results@#The RT-PCR results showed that the relative expression levels of HMGA2 mRNA in the renal carcinoma, benign renal tumor tissues, and adjacent normal renal tissues were 0.84±0.23, 0.19± 0.06 and 0.08±0.04, respectively, and the expression in renal carcinoma tissue was significantly higher than those of the other 2 groups (P<0.01). The Western blot results showed that the relative expression levels of HMGA2 protein in the renal carcinoma, benign renal tumor tissues, and adjacent normal renal tissues were 0.91±0.24, 0.12±0.04 and 0.03±0.01, respectively, and the expression in renal carcinoma tissue was significantly higher than those of the other 2 groups (P<0.01). Immunohistochemical results showed that the expression of HMGA2 protein exhibited brown and tan granular, which mainly distributed in the cell nuclei. Among the 50 cases of renal carcinoma, 34 cases exhibited positive expression, with a positive rate of 68.0%. Among the 40 cases of benign tumor tissues, 3 cases had positive expression, with a positive rate of 7.5%, while among the 50 cases of adjacent normal renal tissues, there was only 1 case exhibiting positive expression of HMGA2 protein, with a positive rate of 2.0%. The protein expression of HMGA2 was significantly higher in the renal carcinoma than in the benign tumors and normal renal tissues (P=0.004). There was no statistically significant difference in the association of HMGA2 protein expressions with age, sex, tumor size and histological type (P>0.05), while significant difference did exist in the association with different statuses of TNM staging and lymph node metastasis (P<0.05). The median time to progression (TTP) in 34 HMGA2 protein-positive patients was (22.36±1.48) months and that of 16 HMGA2 protein-negative patients was (34.55±1.87) months (P<0.05).@*Conclusions@#HMGA2 plays an important role in the tumorigenesis and development of renal carcinoma, and may be used as an important predictor for estimating the prognosis of renal carcinoma. HMGA2 might become a new diagnostic and prognostic marker for renal carcinoma.

Effects of immediate versus delayed post space preparation on coronal microleakage using different filling materials / 中国组织工程研究

BACKGROUND: At present, there is no consensus on the timing of post space preparation in the clinical medical treatment. But it can be inferred from some studies that post space preparation may affect coronal microleakage using different fil ing materials. OBJECTIVE: To compare the effects of immediate post space preparation and delayed post space preparation restoration on coronal microleakage using different fil ing materials. METHODS: Forty-eight extracted and single-rooted premolars were randomly divided into six groups (n=8 per group): premolars were fil ed with AH-plus paste and gutta-percha with the immediate post space preparation as group A1; premolars fil ed with mineral trioxide aggregate paste and gutta-percha with the immediate post space preparation as group A2; premolars fil ed with AH-plus paste and gutta-percha with the delayed post space preparation 1 week later as group B1; premolars fil ed with mineral trioxide aggregate paste and gutta-percha with the delayed post space preparation after 1 week later as group B2;premolars fil ed with AH-plus paste and gutta-percha as negative control group; premolars fil ed with gutta-percha as positive control group. Afterwards, al specimens were soaked for 4 weeks under simulated oral environment to measure the length of coronal microleakage by pressurized dye penetration method. RESULTS AND CONCLUSION: No coronal microleakage was found in the negative control group, but serious coronal microleakage occurred in the positive control group involving the entire root canal. And there was no significant difference in the length of coronal microleakage between group A2 and B2, as wel as between group A1 and A2 (P > 0.05); but the length of coronal microleakage in the group A1 and B2 was significantly less than that in the group B1 (P < 0.05). These results show that the delayed post space preparation has overt effect on the coronal microleakage of root canal fil ed with AH-plus paste.

Preferential conduction to right ventricular outflow track leads to left bundle-branch block morphology in patient with premature ventricular contraction originating from the aortic sinus cusp / 中华心血管病杂志

<p><b>OBJECTIVE</b>The purpose of this study was to explore the relationship between originate and breakout and radiofrequency catheter ablation strategy in patients undergoing radiofrequency ablation for premature ventricular contractions originating from the aortic sinus cusp (ASC) using 3-dimensional electro anatomic mapping.</p><p><b>METHODS</b>This study included 21 consecutive patients (10 male) underwent ablation for frequent PVCs originating from ASC in our hospital between May 2009 and February 2012. Electro anatomic mapping and ablation of right ventricular outflow track (RVOT) and left ventricular outflow track (LVOT) were performed with the 7F 4-mm-tip ablation catheter from right femoral vein and artery. Activation mapping and pacing mapping were performed in all patients.</p><p><b>RESULTS</b>Ablation was successful in all 21 patients successful ablation target in left coronary sinus cusp (LCC, n = 17), in right coronary sinus cusp (RCC, n = 2) and in noncoronary sinus cusp (NCC, n = 2). Seven patients showed a RBBB morphology (group A) and 14 patients showed a LBBB morphology (group B). In group A, earliest ventricular activation (EVA) was recorded 22 - 34 (27.4 ± 4.6) ms earlier before QRS at the site of catheter ablation in ASC. In group B, EVA was later in RVOT than that in ASC in 5 patients and EVA at the site of catheter ablation in RVOT and ASC was 22 - 28 (25.2 ± 2.7) ms and 26 - 40 (32.8 ± 5.2) ms, respectively (t = -3.6, P = 0.024) while EVA was earlier in the remaining 9 patients and EVA recorded in RVOT and ASC was 22 - 38 (28.7 ± 5.9) ms and 18 - 28 (22.7 ± 3.6) ms, respectively (t = 3.8, P = 0.005).</p><p><b>CONCLUSION</b>Patients with premature ventricular contractions originating from the ASC often show preferential conduction to the RVOT, which may explain the LBBB morphology of ECG in these patients.</p>

Radiofrequency catheter ablation of the premature ventricular contractions originating from His bundle region / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the electrocardiogram and 3-dimensional electroanatomic mapping features and radiofrequency catheter ablation efficacy of patients with premature ventricular contractions (PVCs ) originating from His bundle region.</p><p><b>METHODS</b>Between February 2009 and February 2011, 10 consecutive patients ( 4 male, aged from 19 to 59 years) who underwent ablation for frequent PVCs originating close to His bundle region in our department were included. Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm-tip ablation catheter.</p><p><b>RESULTS</b>Among these 10 patients with PVCs originating from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC. Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and 1 patient with PVCs originated from NCC showed RBBB morphology. At the successful ablation sites, local ventricular activation v wave was detected 22-52 (32.6 ± 10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance between target and His bundle was 5.0-8.4(7.0 ± 1.1)mm. Ablation was successful in all 10 patients without complications (PVCs < 500 beats/24 h post ablation).</p><p><b>CONCLUSION</b>PVCs originating near the His bundle have similar electrocardiographic and electrophysiological characteristics for PVSc originated from the RVOT or ASC. Because of the close anatomical relationship between RVOT and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the site of PVCs origin and to guild successful ablation.</p>

Value of identifying the slow conduction zone of idiopathic left ventricular tachycardia by electroanatomic mapping / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the value of identifying slow conduction zone(SCZ) of idiopathic left ventricular tachycardia(ILVT) by electroanatomic mapping.</p><p><b>METHODS</b>Twelve patients with ILVT were mapped by a 3-dimensional electroanatomic (EA) mapping system. Left posterior fascicular potential (PP) and the SCZ with diastolic potential (DP) in LV during sinus rhythm (SR) and ventricular tachycardia (VT) were mapped after a three-dimensional endocardial geometry of the left ventricular was established. Then we investigated the electrophysiological and anatomic characteristics of SCZ.</p><p><b>RESULTS</b>EA mapping was successfully performed in 9 patients during SR and VT, and in 3 patients during VT. The SCZ with DP was located at the inferoposterior septum, and the length of the SCZ was (25.1 ± 2.2) mm with a conduction velocity of (0.08 ± 0.01) m/s. There was no difference in these parameters between patients during SR and VT (P > 0.05). There was one area with PP located at the posterior septum. The areas with both DP and PP were found in 9 patients during SR and VT. In addition, this area was coincided with such area during VT during SR and radiofrequency ablation targeting the site within the area abolished VT in all patients.</p><p><b>CONCLUSIONS</b>The ILVT substrate within the junction area of the SCZ and the posterior fascicular can be identified by EA mapping and used to guide the ablation of ILVT.</p>

Retrospective analysis on the clinical features and management of acute and subacute right ventricular perforation by pacemaker lead / 中华心血管病杂志

<p><b>OBJECTIVE</b>To describe the clinical characteristics and management of the acute and subacute cardiac perforation by pacing leads.</p><p><b>METHODS</b>We retrospectively analyzed clinical data of patients with acute and subacute right ventricular perforation by pacemaker lead occurred in our hospital between 2006 and 2011.</p><p><b>RESULTS</b>Seven cases of confirmed acute and subacute right ventricular perforation by pacemaker lead were enrolled. The perforation rate was 0.15%, 2 cases of perforation occurred during the procedure. The main manifestation was low blood pressure and pericardial effusion. These two patients with cardiac tamponade underwent urgent percutaneous pericardiocentesis and patients recovered without complication. The remaining 5 cases of perforation occurred within 4-16 days after the pacemaker implantation. The main symptoms were diaphragm stimulation and chest pain. Signs of leads dysfunction were observed in all 5 patients. The diagnosis of cardiac perforation was confirmed by chest X-ray, echocardiography, or computed tomography. In all these 5 patients, the leads were removed by simple traction under fluoroscopic guidance with surgical backup support, no complication was observed.</p><p><b>CONCLUSION</b>Acute and subacute right ventricular perforation is a rare but serious complication of pacemaker implantation. In most patients, the leads can be safely removed under fluoroscopic guidance with surgical backup support and close monitoring.</p>

Management of refractory ventricular tachycardia in patients with non-myxomas primary cardiac tumors / 中华心血管病杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics and treatment experience of patients with non-myxomas primary cardiac tumors accompanied with refractory ventricular tachycardia (VT).</p><p><b>METHODS</b>Clinical and imaging data as well as therapy efficacy and outcome were analyzed in 10 patients with non-myxomas primary cardiac tumors accompanied with refractory VT.</p><p><b>RESULTS</b>There were 5 male and 5 female patients in this cohort [mean age (37.6±18.2) years]. Palpitation was presented in all 10 patients, 7 patients experienced syncope, and 2 patients suffered from amaurosis. The diagnosis was made by combined use of transthoracic echocardiograms, MRI, and CT scan. The time from symptom to diagnosis was (33.2±36.7) months. Symptom-related VT was documented by ECG or Holter monitoring. MRI suggested lipoma in 7 patients, lymphoma in 1 patient and fibroma in another patient. Seven tumors were located in the left ventricle, 1 in right atria, 1 at peri-aortic root and 1 near right ventricular outflow tract. Nine out of 10 patients received anti-arrhythmic drug therapy. The ventricular tachyarrhythmia disappeared after surgical tumor resection in 4 patients. All other patients who were treated with antiarrhythmic drugs, radiofrequency ablation or subtotal excision showed only suboptimal efficacy during (39.4±25.1) months follow-up.</p><p><b>CONCLUSION</b>Surgical tumor removal is the best treatment strategy for the treatment of refractory ventricular tachycardia in patients with primary cardiac benign tumors.</p>

The effects of paeoniflorin monomer of a Chinese herb on cardiac ion channels / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Because of the potential proarrhythmic effect of current antiarrhythmic drugs, it is still desirable to find safer antiarrhythmic drugs worldwide. Paeoniflorin is one of the Chinese herb monomers that have different effects on many ion channels. The present study aimed to determine the effects of paeoniflorin on cardiac ion channels.</p><p><b>METHODS</b>Whole-cell patch-clamp technique was used to record ion channel currents. L-type calcium current (I(Ca-L)), inward rectifier potassium current (I(K1)), and transient outward potassium current (I(to1)) were studied in rat ventricular myocytes and sodium current (I(Na)), slow delayed rectifier current (I(Ks)), and HERG current (I(Kr)) were investigated in transfected human embryonic kidney 293 cells.</p><p><b>RESULTS</b>One hundred µmol/L paeoniflorin reduced the peak I(Ca-L) by 40.29% at the test potential of +10 mV (from (-9.78 ± 0.52) pA/pF to (-5.84 ± 0.89) pA/pF, n = 5, P = 0.028). The steady-state activation curve was shifted to more positive potential in the presence of the drug. The half activation potentials were (-11.22 ± 0.27) mV vs. (-5.95 ± 0.84) mV (n = 5, P = 0.007), respectively. However, the steady-state inactivation and the time course of recovery from inactivation were not changed. One hundred µmol/L paeoniflorin completely inhibited the peak I(Na) and the effect was reversible. Moreover, paeoniflorin inhibited the I(K1) by 30.13% at the test potential of -100 mV (from -25.26 ± 8.21) pA/pF to (-17.65 ± 6.52) pA/pF, n = 6, P = 0.015) without effects on the reversal potential and the rectification property. By contrast, 100 µmol/L paeoniflorin had no effects on I(to1), I(Ks) or I(Kr) channels.</p><p><b>CONCLUSIONS</b>The study demonstrated that paeoniflorin blocked I(Ca-L), I(Na), and I(K1) without affecting I(to1), I(Ks), or I(Kr). The multi-channel block effect may account for its antiarrhythmic effects with less proarrhythmic potential.</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>

Clinical characteristics and outcome of 32 patients with long-QT syndrome accompanied with torsade de pointes / 中华心血管病杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics and outcome of patients with long-QT syndrome (LQTs) accompanied with torsade de pointes.</p><p><b>METHODS</b>Thirty-two eligible patients were included in this study. Clinical and electrocardiographic data were analyzed and telephone or out-patient follow-up were made in all patients.</p><p><b>RESULTS</b>There were 15 patients with inherited LQTs (h-LQTs) and 17 patients with acquired LQTs (a-LQTs). There are more women (n = 24) than men (n = 8). β blockers, potassium and magnesium supplement were the basic therapy for h-LQTs patients, bivent pacemaker was implanted in 2 patients and implantable cardioverter defibrillator was implanted in 5 patients. Ventricular tachyarrhythmias and syncope occurred in 4 patients during (39.4 ± 25.1) months follow-up. In 17 a-LQTs patients, one patient with dilated cardiomyopathy died suddenly and another patient with implanted cardioverter defibrillator experienced one ventricular tachycardia during (30.9 ± 13.3) months follow-up.</p><p><b>CONCLUSIONS</b>The prognosis in h-LQTs and a-LQTs patients with structure heart disease is poor. ICD or CRT-D therapy is suggestive for a-LQTs patients with structure heart disease.</p>

Effects of Xinjining extract on inward rectifier potassium current in ventricular myocytes of guinea pig / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level.</p><p><b>METHODS</b>Single VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV.</p><p><b>RESULTS</b>The suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance.</p><p><b>CONCLUSION</b>XJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.</p>

Nifekalant hydrochloride terminating sustained ventricular tachycardia accompanied with QT dispersion prolongation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ventricular tachycardia (VT) and ventricular fibrillation are the main reasons causing sudden cardiac death. This study aimed to investigate the effects of nifekalant hydrochloride (NIF) on QT dispersion (QTd) in treating VT.</p><p><b>METHODS</b>A total of 16 consecutive patients suffered sustained VT was included and then randomly divided into two groups according to the administration duration of NIF. In long-time group (group L), patients were injected with NIF continuously for at least 12 hours after a bolus dose. The patients in short-time group (group S) were injected with NIF just for 1 hour.</p><p><b>RESULTS</b>There were 7 of all 10 episodes of VT which were terminated by NIF, including 4 episodes in group L were stopped over 1 hour after continuous infusion of NIF. One patient suffered from torsade de pointes. Electrocardiography analysis indicated that QTd was significantly decreased 12 hours after stopping of infusing NIF compared with that when VT stopped ((45.4 +/- 22.1) ms vs. (73.4 +/- 33.2) ms, P < 0.01), and the corrected QTd (QTcd) decreased too ((47.8 +/- 22.9) ms vs. (78.3 +/- 36.5) ms, P < 0.01). There was a positive correlation between the increase in QTd and dose of administrating NIF (P < 0.01), so was QTcd (P < 0.01).</p><p><b>CONCLUSIONS</b>More administration of NIF indicates higher terminating rate of VT and more QTd prolongation. However, the safety is acceptable if several important issues were noticed in using NIF, such as serum potassium concentration, stopping side-effect related agents, and carefully observing clinical responses.</p>

Connexin 43 remodeling induced by LMNA gene mutation Glu82Lys in familial dilated cardiomyopathy with atrial ventricular block / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mutations in the lamin A/C gene (LMNA) may cause familial dilated cardiomyopathy (dilated cardiomyopathy) characterized by early onset atrio-ventricular block (A-V block) before the manifestation of dilated cardiomyopathy and high risk of sudden death due to ventricular arrhythmia, which is very similar to the phenotype of gap junction related heart disease. This study aimed to determine the expression and localization of connexins in neonatal myocytes transfected with wild-type (WT) or mutant LMNA to elucidate how these mutations cause heart diseases.</p><p><b>METHODS</b>We studied the connexin 43 (Cx43) and connexin 40 (Cx40) expression in cultured neonatal myocytes transfected with wild-type (WT) or mutant LMNA (Glu82Lys (E82K) and Arg644Cys (R644C)) using confocal imaging and Western blotting analysis.</p><p><b>RESULTS</b>Cx43 protein expression was reduced by 40% in cells transfected with LMNA E82K than that in cells transfected with WT LMNA cDNA. Confocal imaging showed that the Cx43 located inside the cells by LMNA E82K. By contrast, LMNA E82K mutation had no effect on expression and localization of Cx40. LMNA R644C transfection did not show any significant effects on gap junctions at all.</p><p><b>CONCLUSIONS</b>Our findings suggest that LMNA E82K significantly reduced the Cx43 expression and altered its localization which may be one of the pathological mechanisms underlying LMNA-related heart disease.</p>

Beta2-adrenoceptor gene variant Arg16Gly is associated with idiopathic ventricular outflow-tract tachycardia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Imbalance of the sympathetic nervous system was involved in the pathogenesis of idiopathic ventricular outflow-tract tachycardia (IVOT). We aimed to investigate whether the major genetic variants in β(1)- and β(2)-adrenoceptors and GNB3 C825T were associated with IVOT and verapamil sensitive idiopathic left ventricular tachycardia (ILVT).</p><p><b>METHODS</b>Patients with IVOT and ILVT from December 2005 to December 2007 were consecutively enrolled into this study. Controls were randomly selected from the community-based inhabitants. Five genetic variants, Ser49Gly and Gly389Arg in the β(1)-adrenoceptor, Arg16Gly and Gln27Glu in the β(2)-adrenoceptor and GNB3 C825T, were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis.</p><p><b>RESULTS</b>A total of 227 patients with IVOT and 110 patients with ILVT were included. Genotyping revealed that the 16Gly allele of Arg16Gly variant of β(2)-adrenoceptor was associated with a higher risk of IVOT (OR: 1.40, 95%CI: 1.12 - 1.75, P = 0.003 in the addictive model and OR: 1.62, 95%CI: 1.14 - 2.31, P = 0.007 in the dominant model). Patients with Gly16Gln27 haplotype also had a higher risk of IVOT (OR: 1.38, 95%CI: 1.11 - 1.73, P = 0.012). Other four variants, including Ser49Gly and Arg389Gly in β(1)-adrenoceptor, Gln27Glu in β(2)-adrenoceptor and GNB3 C825T, did not differ between patients with IVOT and controls. In patients with ILVT, no significant difference was found in these five variants compared with controls.</p><p><b>CONCLUSIONS</b>Arg16Gly in β(2)-adrenoceptor is significantly associated with IVOT in Chinese Han population. Major genetic variants in β(1)- and β(2)-adrenoceptor and GNB3 C825T may not be associated with ILVT. These data suggest a different arrhythmogenic mechanism in IVOT and ILVT.</p>

Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels.</p><p><b>METHODS</b>The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP).</p><p><b>RESULTS</b>SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change.</p><p><b>CONCLUSIONS</b>The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.</p>