Quality control of postoperative radiotherapy for non-small cell lung cancer: A study of mediastinal shift.

PURPOSE: This study aimed to assess the shifting patterns of the mediastinum, including the target volume and the isocenter point during the postoperative radiotherapy (PORT) process of non-small cell lung cancer (NSCLC), and to observe the occurrence of radiation injury. Additionally, we investigated the significance of mid-term assessment during the implementation of the PORT process. MATERIAL AND METHODS: We established coordinate axes based on bone anatomy and measured the mediastinum's three-dimensional direction and the shift of the isocenter point's shift in the PORT process. Statistical analysis was performed using Wilcoxon, Kruskal-Wallis, and the Chi-square test. P<0.05 was considered statistically significant. RESULTS: In this study, the analysis of patients revealed that the shift of anterior and posterior mediastinum (X), left and right mediastinum (Y), upper and lower mediastinum (Z), anterior and posterior isocenter point (Xi), and the left and right isocenter points (Yi) in the PORT process were 0.04-0.53, 0.00-0.84, 0.00-1.27, 0.01-0.86, and 0.00-0.66cm, respectively. The shift distance of the mediastinum was Z>Y>X, and the shift distance of the isocenter point was Xi>Yi. According to the ROC curve, the cut-off values were 0.263, 0.352, 0.405, 0.238, and 0.258, respectively, which were more significant than the cut-off values in 25 cases (25%), 30 cases (30%), 30 cases (30%), 17 cases (17%), and 15 cases (15%). In addition, there was a significant difference in the shift of the mediastinum and the isocenter point (all P=0.00). Kruskal-Wallis test showed no statistically significant difference between mediastinal shift and resection site in X, Y, and Z directions (P=0.355, P=0.239, P=0.256), surgical method (P=0.241, P=0.110, P=0.064). There was no significant difference in the incidence of RE and RP in PORT patients (P>0.05). No III-IV RP occurred. However, the incidence of ≥ grade III RE in the modified plan cases after M-S was significantly lower than in the original PORT patients, 0% and 7%, respectively (P=0.000). CONCLUSION: In conclusion, this study provides evidence that mediastinal shift is a potential complication during the PORT process for patients with N2 stage or R1-2 resection following radical resection of NSCLC. This shift affects about 20-30% of patients, manifesting as actual radiation damage to normal tissue and reducing the local control rate. Therefore, mid-term repositioning of the PORT and revision of the target volume and radiation therapy plan can aid in maintaining QA and QC during the treatment of NSCLC patients and may result in improved patient outcomes.

[Clinical and genotypic analysis of hereditary spherocytosis combined with cholestasis among pediatric patients].

Objective: To understand the clinical and genetic characteristics of hereditary spherocytosis (HS) combined with cholestasis among pediatric patients. Methods: 12 cases of HS children accompanied by cholestasis at Hunan Children's Hospital were selected as the research subjects between January 2013 and December 2022. Clinical data were collected. Whole-exome sequencing was performed by second-generation sequencing. Suspected pathogenic mutation sites were verified by Sanger sequencing. Results: All pediatric patients were admitted to the hospital due to their yellow skin tone. Eight cases (66.67%) had a positive family history. The clinical manifestations were jaundice, splenomegaly (12/12), abdominal pain, anemia (4/12), and hepatomegaly (5/12). All pediatric patients had decreased hemoglobin, an increased reticulocyte ratio, total bilirubin and direct bilirubin, a positive erythrocyte fragility test, and remarkable spherical erythrocytes in their peripheral blood. Seven cases had elevated aminotransferase; four cases had severely elevated aminotransferase and bilirubin; eight cases had biliary calculi; and two cases had a dilated biliary tract. Liver pathological examination showed mild damage to the liver cells (G1S1) in three pediatric cases. Five children had a total of six unreported mutations: SPTB gene c.2431_2450del, c.4974-2A > G, c.2575G > A, and exon 22-35 deletion; ANK1 gene: c.2379-2380delC; and c .6dupC. Children still had abnormal bilirubin levels following treatment. Two pediatric cases underwent splenectomy. Bilirubin and hemoglobin levels returned to normal after surgery. Conclusion: Children with HS may experience cholestasis, and those with poor treatment results may consider undergoing a splenectomy. Six new types of variants have expanded the HS gene mutation spectrum.

Global, regional, and national time trends in myocarditis-related mortality, 1990-2019: An age-period-cohort analysis.

OBJECTIVE: The aim of this study was to analyze the tendency of myocarditis mortality in 204 countries and areas during the last three decades and its connection with age, epoch, and birth cohort. MATERIALS AND METHODS: The Global Burden of Disease 2019 Study acquired a cause-specific myocarditis mortality estimate. The net drift, as well as the influence caused by age, period, and birth cohort, were evaluated by the age-period-cohort model. Additionally, we analyzed the tendency in research intensity and international collaboration across countries using 3,983 myocarditis-related publications from four periods during 1990-2019. RESULTS: During the last three decades, 101 of 204 countries and areas experienced an increase (net drifts ≥0.0%) or stagnant declines (≥-0.5%) in the death rate. In particular, increasing death rate was generally discovered in most countries whose Socio-demographic indexes (SDIs) are high and middle-high, such as the United States [net drift=2.11% (95% CI 1.71-2.51)] and Italy [2.65% (1.24-4.08)]. Countries with a higher number of deaths were more active in this field of study, such as the United States (237 publications), China (120), and Italy (73). The United States and Italy, whose total link strengths were 209 and 135, respectively, were more active in international collaborative studies. CONCLUSIONS: Despite the global decrease in myocarditis death rate during the last three decades, negative period and cohort effects and elevated mortality were discovered in numerous countries, especially in those whose SDIs were high, and the age distribution of deaths shifted from adolescent to middle-aged and older populations. We also observed a decline in myocarditis research in some countries with increased mortality.

[Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer].

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

[Study on the diagnostic value of transient elastography, APRI and FIB-4 for liver fibrosis in children with non-alcoholic fatty liver disease].

Objective: To evaluate the diagnostic value of transient elastography, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) for liver fibrosis in children with non-alcoholic fatty liver disease (NAFLD). Methods: A retrospective study was conducted on 100 cases of nonalcoholic fatty liver disease in Hunan Children's Hospital between August 2015 to October 2020 to collect liver tissue pathological and clinical data. The receiver operating characteristic curve (ROC curve) was used to analyze the diagnostic value of liver stiffness measurement (LSM), APRI and FIB-4 in the diagnosis of different stages of liver fibrosis caused by NAFLD in children. Results: The area under the ROC curve (AUC) value of LSM, APRI and FIB-4 for diagnosing liver fibrosis (S≥1) were 0.701 [95% confidence interval (CI): 0.579 ~ 0.822, P = 0.011], 0.606 (95%CI: 0.436 ~ 0.775, P = 0.182), and 0.568 (95%CI: 0.397 ~ 0.740, P = 0.387), respectively. The best cut-off values were 6.65 kPa, 21.20, and 0.18, respectively. The AUCs value of LSM, APRI, and FIB-4 for diagnosing significant liver fibrosis (S≥ 2) were 0.660 (95% CI: 0.552 ~ 0.768, P = 0.006), 0.578 (95% CI: 0.464 ~ 0.691, P = 0.182) and 0.541 (95% CI: 0.427 ~ 0.655, P = 0.482), respectively. The best cut-off values were 7.35kpa, 24.78 and 0.22, respectively. The AUCs value of LSM, APRI and FIB-4 for the diagnosis of advanced liver fibrosis (S≥ 3) were 0.639 (95% CI: 0.446 ~ 0.832, P = 0.134), 0.613 (95% CI: 0.447 ~ 0.779, P = 0.223) and 0.587 (95% CI: 0.411 ~ 0.764, P = 0.346), respectively. The best cut-off values were 8.55kpa, 26.66 and 0.27, respectively. Conclusion: The transient elastography technique has a better diagnostic value than APRI and FIB-4 for liver fibrosis in children with NAFLD.

[Clinical analysis of re-operative management for residual partial anomalous pulmonary venous connection after previous cardiac surgery].

Objectives: To analyze the reasons of residual partial anomalous pulmonary venous connection (PAPVC) after previous cardiac surgery, and summarize the strategies and experience for diagnosis and treatment of secondary correction operation. Methods: The clinical data of 18 patients who were admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and Fuwai Yunnan Cardiovascular Hospital from June 2009 to May 2019 were retrospectively analyzed. All the patients underwent secondary cardiac surgery to treat PAPVC. The preoperative and intraoperative characteristics and postoperative complications of the patients were summarized and analyzed. Results: Totally, there were 7 male and 11 female cases, aged 1-49 years (median age: 4.5 years). In the first cardiac surgery, 3 patients were diagnosed with PAPVC, which existed after surgery. One patient was diagnosed with total anomalous pulmonary venous connection (TAPVC), but left PAPVC after surgery. The remaining 14 patients were all missed preoperative and intraoperative diagnosis. After the initial surgery, most patients had no significant symptoms (11/18), but PAPVC was found in 11 cases due to postoperative cardiac murmur or transthoracic echocardiography (TTE). In the secondary surgery, there were 4 cases of type A, 10 cases of type B, 2 cases of type C, no type D, and 2 cases of mixed type, respectively, according to Bordy classification. The diagnostic accuracy of TTE and CT angiography (CTA) was 50.0% and 92.9%, respectively. There was no death after the second surgery, but pulmonary vein occlusion, pericardial effusion, anastomotic stenosis and other complications occurred in 4 patients. Conclusions: The main causes of missed diagnosis of PAPVC are the undefined cardiac structural deformities before operation and the lack of careful exploration during the operation. TTE is simple and feasible to diagnose PAPVC, and it can improve the diagnostic accuracy when combined with CTA.

[Outcomes and the role of adjuvant therapy of limited stage small cell lung cancer undergoing surgical treatment].

Objective: To investigate the outcomes of limited stage small cell lung cancer (L-SCLC) undergoing surgical therapy and to explore the value of adjuvant therapy for those patients. Methods: A retrospective analysis was initialed for the L-SCLC patients who underwent the surgical treatment in the Zhongnan Hospital of Wuhan University from January 2012 to December 2018. The median disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method. Cox regression was used to explore the prognostic factors. Results: A total of 44 patients were included in our study. The median DFS was 25 months, 1- and 2-year DFS rate were 70.2% and 51.9%, respectively. The median OS was 41 months, 1- and 2- year OS rate were 88.4% and 69.9%, respectively. Multivariate analysis showed male (RR=6.56, P=0.03), T3-4 (RR=6.23, P=0.01), pathological lymph node metastasis (RR=6.52, P=0.03) and adjuvant radiotherapy (RR=0.13, P=0.002) were associated with disease relapse significantly. Moreover, pathological lymph node metastasis (RR=3.62, P=0.01) coupled with sufficient adjuvant chemotherapy (≥4 cycles) (RR=0.12, P=0.01) were independent prognostic factors of OS. Conclusions: Surgical therapy may be an alternative primary treatment for L-SCLC. Additional adjuvant radiotherapy can reduce the risk of recurrence. Giving sufficient course of adjuvant chemotherapy can improve OS.

[Safety and efficacy of percutaneous intervention for children with combined congenital heart abnormality solely guided by transthoracic echocardiography].

Objective: To investigate the safety and efficacy of percutaneous intervention of children with combined congenital heart abnormality solely guided by transthoracic echocardiography (TTE) . Methods: From September 2015 to June 2017, 21 children with combined congenital heart abnormality undergoing percutaneous interventional guided by TTE in Fuwai hospital were enrolled in our study, and the clinical data were retrospective analyzed. The atrial septal defect(ASD) closure, ventricular septal defect(VSD) closure, patent ductus arteriosus(PDA) closure or balloon pulmonary valvuloplasty were performed under the guidance of TTE. The procedural effect was evaluated by TTE after operation. The patients were followed up after discharged from the hospital. Results: The age was (37.3±11.6) months, and there were 9 male and 12 female patients. There were 4 cases with ASD and VSD, 6 cases with VSD and PDA, 6 cases with ASD and PDA, 2 cases with VSD and pulmonary stenosis, 3 cases with ASD and pulmonary stenosis. The operations were successfully performed in all patients. No one required extra X ray guidance or open heart surgery. The operation time was (44.6±7.5)min. All patients did not require blood transfusion, inotropic support, and analgesia. There were no complications such as peripheral vascular injury and pericardialeffusion after the operation. The length of hospital stay time was (3.5±0.6) days. All patients were recovered well. The follow-up was (17.6±5.2) months, and post-procedural conduction disturbances, residual shunts, occlude fall off, thrombosis, and new onset of valvular regurgitation were not observed in these patients. Conclusion: Percutaneous interventional of children with combined congenital heart abnormality solely guided by TTE is safe and effective, and the procedure can avoid the potential injuries of X ray and contrast agent.

Modelling climate change impacts on nutrients and primary production in coastal waters.

There is high confidence that the anthropogenic increase of atmospheric greenhouse gases (GHGs) is causing modifications in the Earth's climate. Coastal waterbodies such as estuaries, bays and lagoons are among those most affected by the ongoing changes in climate. Being located at the land-sea interface, such waterbodies are subjected to the combined changes in the physical-chemical processes of atmosphere, upstream land and coastal waters. Particularly, climate change is expected to alter phytoplankton communities by changing their environmental drivers (especially climate-related), thus exacerbating the symptoms of eutrophication events, such as hypoxia, harmful algal blooms (HAB) and loss of habitat. A better understanding of the links between climate-related drivers and phytoplankton is therefore necessary for projecting climate change impacts on aquatic ecosystems. Here we present the case study of the Zero river basin in Italy, one of the main contributors of freshwater and nutrient to the salt-marsh Palude di Cona, a coastal waterbody belonging to the lagoon of Venice. To project the impacts of climate change on freshwater inputs, nutrient loadings and their effects on the phytoplankton community of the receiving waterbody, we formulated and applied an integrated modelling approach made of: climate simulations derived by coupling a General Circulation Model (GCM) and a Regional Climate Model (RCM) under alternative emission scenarios, the hydrological model Soil and Water Assessment Tool (SWAT) and the ecological model AQUATOX. Climate projections point out an increase of precipitations in the winter period and a decrease in the summer months, while temperature shows a significant increase over the whole year. Water discharge and nutrient loads simulated by SWAT show a tendency to increase (decrease) in the winter (summer) period. AQUATOX projects changes in the concentration of nutrients in the salt-marsh Palude di Cona, and variations in the biomass and species of the phytoplankton community.

[Comparison of transthoracic or percutaneous balloon pulmonary valvuloplasty in the therapy of pulmonary valve stenosis].

Objective: To compare the clinical outcome of patients with pulmonary valve stenosis underwent transthoracic and percutaneous balloon pulmonary valvuloplasty. Methods: Clinical data of 806 patients diagnosed as pulmonary valve stenosis underwent transthoracic(171 patients as group A)or percutaneous balloon pulmonary valvuloplasty (635 patients as Group B) in Fuwai Hospital from February 2006 to January 2016 were analyzed retrospectively. There were 72 males in group A (42.1%) and 344 males in group B (54.2%). The average age was (1.6±1.1) years in group A and (21.0±18.5) years in group B. The median weight was 7.65 (7.68) kg (M(Q(R))) in group A and 43.75 (47.38) kg in group B. There were 732 (90.9%) patients followed up from 3 months to 10 years, with an average interval of (6.3±3.6) years. Sixty cases were ligated patent ductus arteriosus simultaneously, and 20 cases got Blalock-Taussig shunt at the same time of valvuloplasty in group A. There were 47 cases of transcatheter closure of atrial septal defect and 6 cases of transcatheter closure of patent ductus arteriosus in group B. The t test, rank sum test and χ(2) test were used to compare data of two groups. Results: There were no hospital death or cardiac tamponade and other serious complications for all patients. The postoperative hospital stayin group A was significantly longer than that in group B (8(5) days vs. 2(2) days, Z=-9.404, P=0.000). In every further consultation, patients were reviewed with transthoracic echocardiography to assess transpulmonary gradient and pulmonary regurgitation. There were significant difference between group A and B of preoperative transpulmonary pressure gradient ((80.6±22.4) mmHg vs.(72.6±20.5) mmHg, t=1.611, P=0.032, 1 mmHg=0.133 kPa) and so as transpulmonary pressure gradient reduction value ((55.9±21.0) mmHg vs. (46.6±23.4) mmHg, t=-1.710, P=0.026). Patients in both groups had good cardiac function during follow-up interval. One patient needed surgical valvuloplasty 10 months after percutaneous balloon pulmonary valvuloplasty and 1 case occurred moderate to severe tricuspid regurgitation in group B. During follow-up period, there was no significant difference between group A and B of transpulmonary pressure gradient ((22.3±6.5) mmHg vs. (25.2±12.6) mmHg, t=1.320, P=0.072), the incidence of pulmonary valve regurgitation in patients of group A was significantly lower than patients of group B (56.1% vs.65.2%, χ(2)=4.755, P=0.029). Conclusions: The clinical outcome and complications are similar between patients underwent two different routes of balloon pulmonary valvuloplasty. Transthoracic balloon pulmonary valvuloplasty is more suitable for infant and underweight children patients with pulmonary valve stenosis. Percutaneous balloon pulmonary valvuloplasty is more suitable for the treatment of the elder children or adults.

[Feasibility of device closure for multiple atrial septal defects using 3D printing and ultrasound-guided intervention technique].

Objective: To investigate the feasibility of trans-catheter closure of multiple atrial septal defects (ASD) monitored by trans-thoracic echocardiography (TTE) under the guidance of 3D printing heart model. Methods: Between April and August 2016, a total of 21 patients (8 male and 13 female) with multiple ASD in Fuwai Hospital of Chinese Academy of Medical Sciences underwent CT scan and 3-dimensional echocardiography for heart disease model produced by 3D printing technique. The best occlusion program was determined through the simulation test on the model. Percutaneous device closure of multiple ASD was performed follow the predetermined program guided by TTE. Clinical follow-up including electrocardiogram and TTE was arranged at 1 month after the procedure. Results: The trans-catheter procedure was successful in all 21 patients using a single atrial septal occluder. Mild residual shunt was found in 5 patient in the immediate postoperative period, 3 of them were disappeared during postoperative follow-up. There was no death, vascular damage, arrhythmia, device migration, thromboembolism, valvular dysfunction during the follow-up period. Conclusion: The use of 3D printing heart model provides a useful reference for transcatheter device closure of multiple ASD achieving through ultrasound-guided intervention technique, which appears to be safe and feasible with good outcomes of short-term follow-up.

[Feasibility and effectiveness of percutaneous ventricular septal defect closure under solely guidance of echocardiography].

Objective: To compare the efficacy and safety of percutaneous ventricular septal defect (VSD) closure under solely guidance of echocardiography and fluoroscopy. Methods: The retrospective study was conducted at Fuwai Hospital, between February 2014 and February 2015. The patients were divided into two groups. VSD closure was conducted in 42 patients under solely guidance of echocardiography, and 100 patients who were treated with percutaneous catheter closure under fluoroscopy guidance were selected as a control group. The baseline characteristics, procedural time and complications were recorded and assessed. Results: There were no significant differences in terms of age, gender and pre-operative echocardiographic characteristics (all P>0.05). Percutaneous VSD closure under traditional fluoroscopy guidance was successful in 95 patients (95%). The procedural time was (54.7±12.5) minutes. The symmetrical occluders diameter was (6.9±1.8) mm. Four patients had postoperative residual shunt, one patient developed left bundle branch block, and 6 patients developed new tricuspid regurgitation. Percutaneous VSD closure under only transthoracic echocardiography (TTE) guidance was successful in 39 patients (93%). Because of delivery catheter passage failure through the defect, one case required conversion to perventricular closure via a small transthoracic incision under transesophageal echocardiography (TEE) guidance. The other two cases underwent surgical repair because of residual shunt with more than 2 mm after closure. The procedural time was (40.3±13.2) minutes. The symmetrical occluders diameter was (6.5±1.2) mm. Four patients had postoperative residual shunt that disappeared after 1 month follow-up, and one patient developed right bundle branch block which disappeared 3 days later. During (9.3±3.6) months follow-up, there were no other complications, such as pericardial effusion, occluder malposition, atrioventricular block, aortic valve regurgitation, and aggravating tricuspid regurgitation in each group. However, the total operation time, diameter of VSD occluder, total mild complications, and the equipment cost in the study group were less than that in the control group (P<0.05). Conclusion: Percutaneous VSD closure can be successfully performed under sole guidance of echocardiography with outcomes similar to those achieved with fluoroscopy guidance.

IL-22-induced antimicrobial peptides are key determinants of mucosal vaccine-induced protection against H. pylori in mice.

Despite the recent description of the mucosal vaccine-induced reduction of Helicobacter pylori natural infection in a phase 3 clinical trial, the absence of immune correlates of protection slows the final development of the vaccine. In this study, we evaluated the role of interleukin (IL)-22 in mucosal vaccine-induced protection. Gastric IL-22 levels were increased in mice intranasally immunized with urease+cholera toxin and challenged with H. felis, as compared with controls. Flow cytometry analysis showed that a peak of CD4+IL-22+IL-17+ T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice. The inhibition of the IL-22 biological activity prevented the vaccine-induced reduction of H. pylori infection. Remarkably, anti-microbial peptides (AMPs) extracted from the stomachs of vaccinated mice, but not from the stomachs of non-immunized or immunized mice, injected with anti-IL-22 antibodies efficiently killed H. pylori in vitro. Finally, H. pylori infection in vaccinated RegIIIß-deficient mice was not reduced as efficiently as in wild-type mice. These results demonstrate that IL-22 has a critical role in vaccine-induced protection, by promoting the expression of AMPs, such as RegIIIß, capable of killing Helicobacter. Therefore, it can be concluded that urease-specific memory Th17/Th22 cells could constitute immune correlates of vaccine protection in humans.

Public Perception of Cadaver Organ Donation in Hunan Province, China.

OBJECTIVE: Our aim was to (1) survey public' perception and attitudes toward organ donation and (2) analyze the relationship between knowledge, attitudes, and willingness to donate. METHODS: We developed a questionnaire, and conducted the survey with stratified random sampling. Overall, 600 residents, aged ≥18 who resided in Hunan, and 600 undergraduates from 3 universities in Hunan were surveyed randomly. For this study, 1085 valid questionnaires were completed, with a response rate of 90.4%. RESULTS: Of the 1085 participants, 581 (53.5%) were students, 504 (46.5%) were residents, and 519 (47.8%) were male and 566 (52.2%) female. The mean accuracy rate was 71.96%, and the students' mean accuracy rate was slightly higher than that of the resident population (73.06% vs 70.68%, respectively). The results showed that 82.2% of public support organ donation, and 53.5% were willing to donate their organs after death. Students scored higher than the residents (88% vs 75.6% and 55.6% vs 51.2%). Nearly 1.8% felt that organ donation was against their religion, 14.9% thought it was important to ensure the integrity of the body, 71.7% agreed that organ donation allowed a positive outcome after a person's death, and 61.5% agreed that organ donation represented a continuation of life, to help families cope with grief. Age and gender were related to attitudes. Public knowledge of organ donation and their attitudes were correlated positively (r = 0.666). CONCLUSIONS: Public knowledge of organ donation is poor, biased, and incomplete, and based on television, movies, and communication networks. Positive attitudes toward donation displayed in the surveys were not matched by actual organ donation.

Potential effects of age on screening for primary aldosteronism.

Aldosterone/renin ratio (ARR) is currently regarded as the most reliable and available screening test for primary aldosteronism (PA), however, the falling accuracy of ARR with increasing age has posed crucial challenge for PA screening among older-aged population. To clarify potential effects of age on screening for PA, 216 subjects with PA and 657 subjects with non-PA were recruited and subdivided into four age groups (⩽39, 40-49, 50-59 and ⩾60 years) and their biochemical parameters were compared. As expected, plasma renin activity (PRA) lowered more than plasma aldosterone concentration (PAC) and led to gradually elevated ARR with increasing age in the non-PA group (P<0.001), whereas this phenomenon was unconspicuous in the PA group. The best cut-off values of ARR for PA screening were elevated in subjects ⩾50 years, whereas the area under the receiver operating characteristic curves (AUCs), sensitivity, specificity and Youden's index (YI) of ARR were declined with increasing age, especially in patients ⩾60 years (AUC=0.863, sensitivity=95.2%, specificity=69.0%, YI=0.643). The AUCs of PAC increased with increasing age and even slightly surpassed that of ARR in patients ⩾60 years (AUCPAC=0.884). Our data suggest that the criteria of ARR for PA screening in patients ⩾50 years may need setting higher; the falling accuracy of ARR with increasing age, especially in patients ⩾60 years, could be improved by taking into account the absolute value of the PAC when applicable by the center.

Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane.

BACKGROUND: The mechanisms by which volatile anaesthetics such as isoflurane alter neuronal function are poorly understood, in particular their presynaptic mechanisms. Presynaptic voltage-gated sodium channels (Na(v)) have been implicated as a target for anaesthetic inhibition of neurotransmitter release. We hypothesize that state-dependent interactions of isoflurane with Na(v) lead to increased inhibition of Na(+) current (I(Na)) during periods of high-frequency neuronal activity. METHODS: The electrophysiological effects of isoflurane, at concentrations equivalent to those used clinically, were measured on recombinant brain-type Na(v)1.2 expressed in ND7/23 neuroblastoma cells and on endogenous Na(v) in isolated rat neurohypophysial nerve terminals. Rate constants determined from experiments on the recombinant channel were used in a simple model of Na(v) gating. RESULTS: At resting membrane potentials, isoflurane depressed peak I(Na) and shifted steady-state inactivation in a hyperpolarizing direction. After membrane depolarization, isoflurane accelerated entry (τ(control)=0.36 [0.03] ms compared with τ(isoflurane)=0.33 [0.05] ms, P<0.05) and slowed recovery (τ(control)=6.9 [1.1] ms compared with τ(isoflurane)=9.0 [1.9] ms, P<0.005) from apparent fast inactivation, resulting in enhanced depression of I(Na), during high-frequency stimulation of both recombinant and endogenous nerve terminal Na(v). A simple model of Na(v) gating involving stabilisation of fast inactivation, accounts for this novel form of activity-dependent block. CONCLUSIONS: Isoflurane stabilises the fast-inactivated state of neuronal Na(v) leading to greater depression of I(Na) during high-frequency stimulation, consistent with enhanced inhibition of fast firing neurones.

Evolution of the HCV viral population from a patient with S282T detected at relapse after sofosbuvir monotherapy.

Clinical phase II/III studies of the nucleotide analogue HCV NS5B inhibitor sofosbuvir (SOF) have demonstrated high efficacy in HCV-infected patients in combination therapy. To date, resistance to SOF (S282T in NS5B) has rarely been detected in patients. In this study, we investigated the evolution of S282T viral variants detected in one HCV genotype 2b-infected patient who relapsed following 12 weeks of SOF monotherapy. Deep sequencing of the NS5B gene was performed on longitudinal plasma samples at baseline, days 2 and 3 on SOF, and longitudinal samples post-SOF treatment through week 48. Intrapatient HCV evolution was analysed by maximum-likelihood phylogenetic analysis. Deep sequencing analysis revealed a low level pre-existence of S282T at 0.05% of viral sequences (4/7755 reads) at baseline and 0.03% (6/23 415 reads) at day 2 on SOF. Viral relapse was detected at week 4 post-treatment where 99.8% of the viral population harboured S282T. Follow-up analysis determined that S282T levels diminished post-treatment reaching undetectable levels 24-48 weeks post-SOF. Phylogenetic analysis together with the persistence of unique post-treatment mutations in all post-SOF samples suggested that growth of wild type resulted from reversion of the S282T mutant to a wild type and not outgrowth of the baseline wild-type population. Our data suggest that a very low level of pre-existing S282T at baseline in this patient was enriched and transiently detected following SOF monotherapy. Despite relapse with drug resistance to SOF, this patient was successfully retreated with SOF plus ribavirin for 12 weeks and is now cured from HCV infection.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.