On Privacy Protection of Electronic Health Records / 中国医学伦理学

With the continuous advancement of health informatization and the wide application of medical big data, electronic health records came into being and spread rapidly. However, because electronic health records contain a large amount of private information, privacy protection is the primary consideration for the sustainable development of electronic health records. By analyzing the shortcomings of privacy protection of electronic health records in law, technology, management and protection consciousness, this paper put forward some countermeasures, such as perfecting the relevant laws and regulations of privacy protection of electronic health records, improving the technical level, improving the management defects of electronic health records, and cultivating the privacy protection consciousness of professionals and the public, so as to improve the overall privacy protection level of China’s health records information management system and provide effective protection for the privacy information of Chinese residents’ electronic health records.

Reduction ascending aortoplasty in adult patients undergoing aortic valve replacement: Aorta diameter change, mid- and long-term clinical results / 中国胸心血管外科临床杂志

@#Objective    To assess mid- and long-term outcomes and share our clinical method of reduction ascending aortoplasty (RAA) in adult patients undergoing aortic valve replacement (AVR). Methods    We retrospectively analyzed clinical data of 41 adult patients with aortic valve disease and ascending aortic dilatation before and after operation of RAA+AVR in Fuwai Hospital from January 2010 to July 2017. There were 28 male and 13 female patients aged 28-76 (53.34±12.06) years. Twenty-three patients received AVR+RAA using the sandwich technique (a sandwich technique group), while other 18 patients received AVR+ascending aorta wrap (a wrapping technique group). Ascending aorta diameter (AAD) was measured by echocardiography or CT scan preoperatively and postoperatively. Results    There was no perioperative death. The mean preoperative AAD in the sandwich technique group and the wrapping technique group (47.04±3.44 mm vs. 46.67±2.83 mm, P=0.709) was not statistically different. The mean postoperative AAD (35.87±3.81 mm vs. 35.50±5.67 mm, P=0.804), and the mean AAD at the end of follow-up (41.26±6.54 mm vs. 38.28±4.79 mm, P=0.113) were also not statistically different between the two groups. There were statistical differences in AAD before, after operation and at follow-up in each group. All 41 patients were followed up for 23-108 (57.07±28.60) months, with a median follow-up of 51.00 months. Compared with that before discharge, the AAD growth rate at the last follow-up was –1.50-6.78 mm/year, with a median growth rate of 0.70 mm/year, and only 3 patients had an annual growth rate of above 3 mm/year. Conclusion    Mid- and long-term outcomes of RAA in adult patients undergoing AVR with both methods are satisfying and encouraging.

Assessment of the internal mammary artery using ultrasound in patients with coronary artery disease before coronary artery bypass grafting / 中国胸心血管外科临床杂志

@#Objective    To investigate the feasibility and effectiveness of using ultrasound to evaluate the internal mammary artery (IMA) and explore the related factors affecting the quality of IMA. Methods    From July 2020 to January 2021, for patients who underwent coronary artery bypass grafting at the Department of Cardiovascular Surgery, Fuwai Hospital, ultrasound was applied to measure bilateral IMA at the parasternal second intercostal space. There were 62 males and 18 females with an average age of 59.9±8.3 years. The clinical data of the patients were recorded and analyzed. Results    A total of 160 IMA were measured. The IMA was detected in 99.4% (159/160), and the one that was not measured was proved to be occluded by enhanced CT. A total of 157 (98.1%) IMA intima were smooth, 2 (1.3%) were found to have uneven intimal thickening and less smooth, and only 1 (0.6%) was occluded. The intravascular diameter, peak systolic flow rate, peak diastolic flow rate, and blood flow rate of the left second intercostal IMA were 1.9±0.3 mm, 66.8±17.7 cm/s, 6.4 (0.0, 9.7) cm/s, 19.7±9.4 mL/min; and those of the right one were 2.1±0.3 mm, 69.7±18.5 cm/s, 6.0 (0.0, 9.2) cm/s and 22.8±11.5 mL/min, respectively. IMA vessel diameter and blood flow were greater on the right than those on the left side in the same individual (P<0.01). In univariate analysis, sex and body surface area were the factors that influenced the size of the IMA vessel among different individuals, and by linear regression analysis, the size of the IMA vessel was only related to body surface area among different individuals. On univariate analysis, diabetes mellitus was the only factor affecting IMA blood flow, with a mean reduction in blood flow of 18.4% (left) and 21.7% (right) in the diabetic group (P<0.05). Conclusion    Preoperative evaluation of the IMA using ultrasound over the parasternal second intercostal space is easy, noninvasive, and has a high success rate. The internal diameter of the IMA is positively correlated with body surface area, and blood flow is significantly reduced in patients with diabetes.

Clinical efficacy of reduction ascending aortoplasty with wedge resection in adult patients undergoing aortic valve replacement: A single-center retrospective study / 中国胸心血管外科临床杂志

@#Objective    To assess mid-term outcomes of reduction ascending aortoplasty (RAA) in adult patients undergoing aortic valve replacement (AVR). Methods    We retrospecctively analyzed clinical data of 30 adult patients with aortic valve diseases and ascending aortic dilatation in Fuwai Hospital from 2010 to 2019. There were 20 males and 10 females with an age of 38-72 (55.73±9.95) years. All patients received AVR+RAA using the wedge resection technique. Ascending aorta diameter (AAD) was measured by echocardiography or CT scan preoperatively and postoperatively. Results    There was no perioperative death. The mean preoperative and postoperative AAD in all patients were 48.23±3.69 mm and 37.60±5.02 mm, respectively. And the mean AAD of follow-up was 40.53±4.65 mm. There was a statistical difference in AAD between preoperation and postoperation, postoperation and final follow-up, preoperation and final follow-up. The median follow-up time was 28.50 (12-114) months. The median rate of increase in AAD postoperatively was 0.76 mm per year. And the rate of increase was ≥3 mm per year in 5 patients, while ≥5 mm per year in 4 patients with indications for reoperation. Conclusion    Mid-term outcomes of RAA in adult patients undergoing aortic valve replacement using the wedge resection technique are satisfying and encouraging. However, some patients still need surgical re-intervention.

The characteristics of trunk muscle activity in patients with Parkinson's disease / 中华物理医学与康复杂志

Objective To explore the characteristics of trunk muscle activity in persons with Parkinson's disease (PD) in search of better treatments for abnormal posture.Methods Ninety persons with PD of different severity and 8 normal controls were studied using surface electromyography (sEMG).A sixteen-lead sEMG instrument was used to collect sEMG amplitudes from the bilateral thoracic erector spinae,lumbar erector spinae,external oblique and rectus abdominis muscles when the subjects were lying,standing and walking.Results Compared with the control group,a significant increase was observed in the sEMG amplitude of the lumbar erector spinal muscle [(18.56±14.57) μV] and rectus abdominis muscles [(24.00±18.80)μV] of the PD group when lying.Significant relative increases in (P＜0.05),of the external oblique muscles were observed [(27.87± 11.49)μV] when standing (P＜0.05),and in the thoracic erector spinae muscle [(58.74±29.69)μV] and external oblique muscles [(59.01± 25.20) μV] increased when walking (P＜0.05).Compared with the control group,the sEMG activity of the external oblique muscles was significantly elevated in PD patients at Hoehn and Yahr stage 1 to 1.5 when walking.One or more of the trunk muscle groups showed significantly greater activity in the PD patients in Hoehn and Yahr stage 2 or 3 in all three positions.Conclusions The sEMG activities of the extensor and flexor muscles increase simultaneously in PD patients.More trunk muscles are involved in PD patients with higher H-Y grades.These findings provide a neurophysiological basis for the customizaton of rehabilitation therapy for patients with Parkinson's disease and for the precise selection of muscles for botulinum toxin injection.

Cemented versus cementless hemiarthroplasty for femoral neck fractures in the elderly / 中国组织工程研究

BACKGROUND: Hemiarthroplasty is widely recommended for the treatment of femoral neck fractures in elderly patients, but it is controversial in choosing cemented or cementless fixation types. OBJECTIVE: To compare the clinical effects of cemented hemiarthroplasty with cementless hemiarthroplasty for the treatment of femoral neck fractures in elderly and to provide a scientific basis for the selection of clinical prosthesis. METHODS: 167 elderly patients with femoral neck fractures undergoing hemiarthroplasty in the Foshan Hospital of Traditional Chinese Medicine from March 2013 to March 2015 were enrolled in this study. According to the type of prosthesis, patients were divided into cementless group (n=81) and cemented group (n=86). The operation time, intraoperative blood loss, hemoglobin levels 1 day after surgery, reoperation rate, mortality and complications at 1 year after surgery were compared. After surgery, clinical function of hip joint was assessed by Harris scoring system. The pain was evaluated by Visual Analogue Scale. RESULTS AND CONCLUSION: (1) All patients were followed up for ≥ 12 months. (2) The operation time in the cementless group was significantly shorter than that in the cemented group (P < 0.01). (3) There was no significant difference in the intraoperative blood loss and hemoglobin levels at postoperative 1 day (P > 0.05). (4) There were no significant differences in Harris hip scores and Visual Analogue Scale score at various time points between both groups (P > 0.05). (5) The incidence of thigh pain in cementless group was slightly higher than that in cemented group at 1 week, 1 and 6 months after operation, but the differences were not statistically significant (P > 0.05). Two patients died from myocardial infarct in the cementless group, and one patient died from pulmonary infection in the cemented group. The mortality was not significantly different at postoperative 1 year between the two groups (P > 0.05). No complications, such as prosthesis loosening and sinking, periprosthetic fracture, and periprosthetic infection, which needed to be refurbished, occurred in both groups. (6) Our findings suggest that both cemented and cementless hemiarthroplasties can obtain satisfactory effect in the treatment of femoral neck fractures in the elderly patients. Cementless hemiarthroplasty can significantly shorten operation time.

Interactions between vitamin D receptor (VDR) gene and Interleukin-6 gene and environment factors on coronary heart disease risk in a Chinese Han population.

AIMS: To investigate the association of several single nucleotide polymorphisms (SNPs) within Interleukin-6 (IL- 6) and vitamin D receptor (VDR) gene, and additional gene- gene and gene- smoking interaction with coronary heart disease (CHD) risk in a Chinese population. METHODS: Hardy-Weinberg equilibrium (HWE) examination was used by SNPstats (http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Stratified analysis for gene- smoking interaction was investigated by logistic regression. RESULTS: CHD risk was significantly higher in carriers with the C allele of rs1800796 within IL-6 gene than those with GG genotype (GC+ CC versus GG), adjusted OR (95%CI) =1.62 (1.19-2.23); CHD risk was also higher in carriers with the T allele of rs2228570 within VDR gene than those with CC genotype (CT+ TT versus CC), adjusted OR (95%CI) = 1.68 (1.26-2.17). However, we did not find any direct associations of the others SNPs in IL- 6 and VDR gene with CHD risk. We also found a significant interaction between rs1800796 and smoking, the cross-validation consistency of this two- locus model was 10/ 10, and the testing accuracy was 60.11%. Current smokers with rs1800796- GC or CC genotype have the highest CHD risk, compared to never- smokers with rs1800796- GG genotype within IL- 6 gene, OR (95%CI) = 2.57 (1.74 -3.46). CONCLUSIONS: We found that the C allele of rs1800796 within IL-6 and T allele of rs2228570 within VDR gene, interaction between rs1800796 and smoking were all associated with increased CHD risk.

A new sesquiterpenoid from the roots of Stelleropsis tianschanica / 药学学报

Three sesquiterpenoids were isolated from the dichloromethane extract of the roots of Stelleropsis tianschanica Pobed through a combination of various chromatographic approaches, including silica gel, Sephadex LH-20, reverse phase C18 and so on. On the basis of spectroscopic data analysis, they were identified as (+)-guaia-l(10),ll-dien-9-one-5α-hydroxy (1), 4β,5βH-guai-9,7(11)-dien-12,8-olide-1α,8α-diol (2), 4α,5βHguai-9,7(11)-dien-12,8-olide-1α,8α-diol (3). The compound 1 is a new sesquiterpenoid, and the compound 3 was isolated for the first time from the genus Stelleropsis.

Relationship between the expression of TIP30 and clinico-pathological characteristics in extrahepatic cholangiocarcinoma / 中国现代普通外科进展

Objective:To investigate the expression of TIP30 and its relationship with clinico-pathological characteristics in patients with extrahepatic cholangiocarcinoma (ECC).Methods:The expression of TIP30 in 78 cases of ECC tissues and 78 cases of para-cancerous tissues were detected by immunohistochemistry.Results:The positive expression rate of TIP30 was 43.59％ and 75.64％ in ECC tissues and para-cancerous tissues,respectively.Differences were statistically significant (P＜ 0.05).The expression levels of TIP30 were not correlated with age,gender,degree of differentiation and tumor size(P＞0.05),but correlated with lymph node metastasis,distant metastasis and TNM staging(P＜ 0.05).The median overall survival of 78 ECC cases was 14.8 months,and it of TIP30 positive expression cases was 20.3 months,statistically higher than 11.5 months in TIP30 negative expression cases(P＜ 0.01).Conclusion:The downregulation of TIP30 is closely correlated with the development,metastasis and prognosis of ECC.TIP30 may be used as a molecular marker to identify and predict the progression,metastasis and prognosis of ECC.

Chemical constituents from roots of Stelleropsis tianschanica / 中国中药杂志

The constituents from 95% ethanol extract of the roots of Stelleropsis tianschanica were purified by column chromatography techniques, leading to the isolation of 17 compounds. Their structures were elucidated by spectroscopic dataas 5'-methoxy lariciresinol(1), pinoresinol(2), daphnoretin(3), acutissimalignan B(4),(+)-secoisolariciresinol(5),(+)-epipinoresinol(6), 7-methyi-daphnoretin(7), thero-8S-7-methoxysyringylglycerol(8), 1-O-methyl-guaiacylglycerol(9), 2R-22'-ferulic acid ester-2,3-dihydroxypropyl ester(10), vesiculosin(11), 4β,5βH-guai-9,7(11)-dien-12,8-olide-1α,8α-diol(12),(-)-nortrachelogenin(13), 4α,5βH-guai-9,7(11)-dien-12,8-olide-1α,8α-diol(14), matairesinol(15), lariciresinol(16)and isolariciresinol(17). Among them, compounds 1-13 wereobtained for the first time fromthe genus Stelleropsis. Compounds 3, 7, 10-14 were tested for their activation of orphan nuclear receptor TR3 with the immunofluorescence technology in 50 μmol•L⁻¹. The results showed that compound 10 displayed moderate activity with the activity ratio of 76.38%, and the others were only about 50.0%.

The neuroprotection of cinepazide maleate on acute cerebral ischemic brain in rats:a proton magnetic spectroscopy study / 中华行为医学与脑科学杂志

Objective To dynamically monitor the effect of Cinepazide maleate (CM) on ischemic region of the brain and to elucidate the neuroprotection of CM on acute cerebral ischemic rat model and related mechanisms.Methods The rat model of acute brain ischemia-reperfusion was established with tighting threads.They were randomly divided into ischemia-reperfusion group and CM treatment group(n=8 in each group).Rats in CM treatment group were given 3 mg / kg CM by caudal intravenous injection immediately after brain ischemia-reperfusion.T2 weighted imaging(T2WI) and proton magnetic resonance spectroscopy (1HMRS) were performed before operation and at 6 hours,24 hours and 3 days after reperfusion.Results At 6 h,24 h and 3 d after operation there was no difference for areas of cerebral ischemia on T2WI between 2 groups.The values of N-acetylaspartate(NAA) (Phosphocreatine(PCr) +Creartine(Cr)) in ischemia-reperfusion group rats were (1.53±0.20),(0.50 ±0.17),(0.44±0.13),(0.40±0.10) before operation and at 6 h,24 h,3 d after operation,respectively.And in CM treatment group the values of NAA/(PCr+Cr) were (1.44±0.22),(0.68±0.13),(0.61±0.10),(0.53±0.09) at the same time points.The values of lactate(Lac)/(PCr+Cr) in ischemia-reperfusion group were (0.03±0.01),(1.10 ±0.28),(1.30± 0.23),(1.23± 0.19) before operation and at 6 h,24 h,3 d after operation,respectively.And in CM treatment group the values of Lac/(PCr+Cr) were (0.02±0.01),(0.85±0.25),(0.99±0.20),(0.90±0.15) at the same time points.The rats in ischemia-reperfusion group had lower value of NAA/(PCr+Cr) (P＜0.01) and higher value of Lac/(PCr+Cr) at all time points after operation than those before operation.Compared with rats in ischemia-reperfusion group,the value of NAA/(PCr+Cr) increased(P＜0.05) and the value of Lac/(PCr+Cr) decreased(P＜0.05) decreased significantly for CM treatment group rats.Conclusion CM treatment can decrease the intracellular accumulation of lactic acid and reduce neuronal necrosis in acute brain ischemia-reperfusion rats.

Interventional treatment of lower extremity arteriosclerosis obliterans / 中华普通外科杂志

Objective To summarize the clinical efficacy of interventional treatment for lower extremity arteriosclerosis obliterans and its complications.Methods We analyzed sixty-nine patients with lower extremities arteriosclerosis obliterans undergoing interventional treatment from October 2011 to January 2013.During the same period,three patients were referred to us who suffered from the complications of interventional treatment.In these patients,eight were TASC ⅡA type,twenty-one were TASC Ⅱ B,twenty TASC Ⅱ C,and twenty-two TASC Ⅱ D lesions.All patients received CTA or DSA.Seventy patients were treated by interventional treatment,and two who had fractured stent underwent external iliacsuperficial femoral artery bypass grafting using artificial grafts.Results The technique success rate was 100％.The symptoms disappeared after surgery.During interventional treatment,one iliac artery ruptured,one patient suffered from arterial perforation and three patients suffered from distal embolization.Sixty-eight patients were followed-up for 9 ± 4 months.Conclusions Endovascular treatment has good early clinical efficacy.In order to reduce the incidence of complications,indication of interventional treatment should be controlled strictly and manipulation should be careful.

The impact of polyclonal neural cell adhesion molecule antibody on the potency of botulinum toxin / 中华物理医学与康复杂志

Objective To investigate the impact of polyclonal neural cell adhesion molecule antibody (P-NCAM-Ab) on the potency of botulinum toxin A (BTX-A).Methods Ninety male Sprague-Dawley rats were randomly divided into 3 equal groups:a normal control group,a BTX-A group and a P-NCAM-Ab group.The rats in the normal control group were injected with 100 μl of saline solution in their right gastrocnemius,while those in the BTX-A and P-NCAM-Ab groups were injected with 100 μl of BTX-A (0.5 U).In addition,the rats in the P-NCAM-Ab group were also injected with 100 μl of P-NCAM-Ab (the dosage was 20 U) at the same site on the 3rd day after the BTX-A injection.The rats' gastrocnemius muscle strength was evaluated with a self-made system for evaluating neuromuscular function before and after the toxin injection,on the 3rd day,as well as 1,2,4,6,8,10 and 12 weeks after the BTX-A injection.Any wet weight changes in the muscles were observed,and immunochemistry methods were employed to observe any structural changes in the motor endplates and nerve fibers at the different time points.Results After the saline injection,the average gastrocnemius muscle strength of the control group increased with time,while strength in the BTX-A and P-NCAM-Ab groups demonstrated a decrease in strength followed by a gradual increase.The average gastrocnemius muscle strength of the rats in the BTX-A and P-NCAM-Ab groups was significantly lower than that of the control group at all time points.Compared with the BTX-A group,the muscle strength of the P-NCAM-Ab group rats decreased further.Strength recovery in the BTX-A and P-NCAM-Ab groups was significantly slower than in the control group.The wet weight percentage in the BTX-A and P-NCAM-Ab groups at first decreased and then recovered with time.After the BTX-A injection,the average wet weight percentage of the P-NCAM-Ab group rats was significantly lower than that of the BTX-A group after 3 days,and 1,2 and 4 weeks.Karnovsky-Roots AchE staining showed that the motor endplates' color in the BTX-A and P-NCAM-Ab groups deepened gradually,though the color of the P-NCAM-Ab group was lighter than that of the BTX-A group at each time point.The mean optical density of the motor endplates' positive reaction area increased with time in both groups,but the P-NCAM-Ab group was lower than that of the BTX-A group at 1,2,4,8 and 12 weeks.Counting the nerve fibers dyed by gold chloride showed similar trends with both experimental groups significantly different from the control group.Conclusion P-NCAM-Ab can increase the potency of BTX-A and prolong its action.

A novel porcine acellular dermal matrix scaffold used in periodontal regeneration / 国际口腔科学杂志·英文版

Regeneration of periodontal tissue is the most promising method for restoring periodontal structures. To find a suitable bioactive three-dimensional scaffold promoting cell proliferation and differentiation is critical in periodontal tissue engineering. The objective of this study was to evaluate the biocompatibility of a novel porcine acellular dermal matrix as periodontal tissue scaffolds both in vitro and in vivo. The scaffolds in this study were purified porcine acellular dermal matrix (PADM) and hydroxyapatite-treated PADM (HA-PADM). The biodegradation patterns of the scaffolds were evaluated in vitro. The biocompatibility of the scaffolds in vivo was assessed by implanting them into the sacrospinal muscle of 20 New Zealand white rabbits. The hPDL cells were cultured with PADM or HA-PADM scaffolds for 3, 7, 14, 21 and 28 days. Cell viability assay, scanning electron microscopy (SEM), hematoxylin and eosin (H&E) staining, immunohistochemistry and confocal microscopy were used to evaluate the biocompatibility of the scaffolds. In vitro, both PADM and HA-PADM scaffolds displayed appropriate biodegradation pattern, and also, demonstrated favorable tissue compatibility without tissue necrosis, fibrosis and other abnormal response. The absorbance readings of the WST-1 assay were increased with the time course, suggesting the cell proliferation in the scaffolds. The hPDL cells attaching, spreading and morphology on the surface of the scaffold were visualized by SEM, H&E staining, immnuohistochemistry and confocal microscopy, demonstrated that hPDL cells were able to grow into the HA-PADM scaffolds and the amount of cells were growing up in the course of time. This study proved that HA-PADM scaffold had good biocompatibility in animals in vivo and appropriate biodegrading characteristics in vitro. The hPDL cells were able to proliferate and migrate into the scaffold. These observations may suggest that HA-PADM scaffold is a potential cell carrier for periodontal tissue regeneration.

Lipid droplet binding of hepatitis C virus core protein genotype 3.

Background. Hepatitis C virus (HCV) genotype 3 is known to cause steatosis (fatty liver) that is more frequent and severe than other genotypes. We previously identified sequence elements within genotype 3 HCV Core domain 3 that were sufficient for lipid accumulation. Aims. We examined various genotype 3 Core domains for lipid droplet localization and compared the lipid droplet binding regions of domain 2 with a genotype 1 isolate. Methods. We generated HCV Core domain constructs fused with green fluorescent protein and performed immunofluorescence to visualize lipid droplets. Results. Constructs containing HCV Core domain 2 are appropriately localized to lipid droplets with varying degrees of efficiency. When compared to genotype 1, there are polymorphisms within domain 2 that do not appear to alter lipid droplet localization. Conclusions. In summary, the differences in a steatosis-associated HCV Core genotype 3 isolate do not appear to involve altered lipid droplet localization.

Comparison of effects of ivabradine versus carvedilol in murine model with the Coxsackievirus B3-induced viral myocarditis.

BACKGROUND: Elevated heart rate is associated with increased cardiovascular morbidity. The selective I(f) current inhibitor ivabradine reduces heart rate without affecting cardiac contractility, and has been shown to be cardioprotective in the failing heart. Ivabradine also exerts some of its beneficial effects by decreasing cardiac proinflammatory cytokines and inhibiting peroxidants and collagen accumulation in atherosclerosis or congestive heart failure. However, the effects of ivabradine in the setting of acute viral myocarditis and on the cytokines, oxidative stress and cardiomyocyte apoptosis have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: The study was designed to compare the effects of ivabradine and carvedilol in acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of ivabradine and carvedilol (a nonselective ß-adrenoceptor antagonist) on myocardial histopathological changes, cardiac function, plasma noradrenaline, cytokine levels, cardiomyocyte apoptosis, malondialdehyde and superoxide dismutase contents were studied. Both ivabradine and carvedilol similarly and significantly reduced heart rate, attenuated myocardial lesions and improved the impairment of left ventricular function. In addition, ivabradine treatment as well as carvedilol treatment showed significant effects on altered myocardial cytokines with a decrease in the amount of plasma noradrenaline. The increased myocardial MCP-1, IL-6, and TNF-α. in the infected mice was significantly attenuated in the ivabradine treatment group. Only carvedilol had significant anti-oxidative and anti-apoptoic effects in coxsackievirus B3-infected mice. CONCLUSIONS/SIGNIFICANCE: These results show that the protective effects of heart rate reduction with ivabradine and carvedilol observed in the acute phase of coxsackievirus B3 murine myocarditis may be due not only to the heart rate reduction itself but also to the downregulation of inflammatory cytokines.

The mechanism of carvedilol in experimental viral myocarditis.

Carvedilol is a nonselective ß-blocker with α1-adrenergic blocking and antioxidant properties. A number of preclinical experiments and clinical trials have demonstrated that carvedilol provides prominent benefit in heart failure. However, less research has been done in the area of animal models of viral myocarditis. This paper reviews the use of carvedilol in animal models of viral myocarditis. The experimental evidence strongly suggests that carvedilol, but not metoprolol (a selective ß1-adrenergic blocking agent), protects against viral myocarditis and the superior cardioprotection effect of carvedilol to metoprolol may be due to its upregulating the production of antiinflammatory cytokines, downregulating the production of proinflammatory cytokines, antioxidative effects, the suppression of matrix metalloproteinases production, and positive hemodynamic effects.

A methodology for dynamic evaluation of the biological efficacy of botulinum toxin and its dose-effect relationship / 中华物理医学与康复杂志

Objective To develop a method for dynamically observing the biological efficacy of botulinum toxin A (BTX-A) and to investigate the dose-effect relationship between BTX-A dosage and muscle strength.MethodsFifty-four male Sprague Dawley rats were randomly divided into 9 groups.Groups 1-7 were injected intramuscularly with 0.1 ml BTX-A (0.01 U to 4.0 U) into the gastrocnemius on the right side.Rats in group 8 were injected intramuscularly with an equal volume of saline solution as the control group,and group 9 was used to determine the location of injection.Gastrocnemius muscle strength was evaluated using a self-made evaluation system before and after the toxin injection and on the 3rd,7th,14th,21st,30th,45th,60th and 75th day following.ResultsMuscle strength reached its lowest level on days 3 to 7,with a significant difference in the decline of muscle strength between the test groups and the control group up to day 60.With the lower BTX-A doses (0.01 U,0.1 U,0.5 U,1.0 U),muscle strength had decreased significantly on the 21st day,but recovered to its initial levels in all groups at the same time.There was no significant difference among the 1.0 U,1.5 U,2.0 U and 4.0 U groups.ConclusionsStandardized gastrocnemius injection combined with neuromuscular functional evaluation can establish a model of BTX-A dosage and muscle paralysis which can be used to assess the evolution of the biological efficacy of BTX-A.

Up-regulation of Hedgehog pathway is associated with cellular permissiveness for hepatitis C virus replication.

UNLABELLED: Studies of the hepatitis C virus (HCV) life-cycle rely heavily on Huh7.5 cells, but the reasons why these cells are exceptionally permissive for HCV replication are not clear. Based on recent clinical observations, we hypothesized that the Hedgehog (Hh) pathway, which has not been previously associated with HCV replication, may be involved in the Huh7.5 phenotype of increased permissiveness. We tested this hypothesis by comparing levels of a variety of Hh-related cellular markers in Huh7.5 cells with the parental Huh7 cells, which are far less permissive. Here we demonstrate that Huh7.5 cells, when compared with Huh7 cells, have substantially decreased expression of epithelial markers, increased levels of mesenchymal markers, and markedly up-regulated Hh pathway activity: Shh, >100-fold, Gli1, >30-fold, Ptc, 2-fold. In Huh7.5 cells, we found that cyclopamine, an Hh pathway antagonist, reduced HCV RNA levels by 50% compared with vehicle and inactive isomer controls. Moreover, in Huh7 cells treatment with recombinant Shh ligand and SAG, both Hh pathway agonists, stimulated HCV replication by 2-fold and 4-fold, respectively. These effects were observed with both viral infections and a subgenomic replicon. Finally, we demonstrated that GDC-0449 decreased HCV RNA levels in a dose-response manner. CONCLUSION: We have identified a relationship between HCV and Hh signaling where up-regulated pathway activity during infection promotes an environment conducive to replication. Given that Hh activity is very low in most hepatocytes, these findings may serve to further shift the model of HCV liver infection from modest widespread replication in hepatocytes to one where a subset of cells support high-level replication. These findings also introduce Hh pathway inhibitors as potential anti-HCV therapeutics.