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Without an effective vaccine against SARS-CoV-2, the build-up of herd immunity through natural infection has been suggested as a means to control COVID-19. Although population immunity is typically estimated by the serological investigation of recovered patients, humoral immunity in asymptomatic subjects has not been well studied, although they represent a large proportion of all SARS-CoV-2 infection cases. In this study, we conducted a serosurvey of asymptomatic infections among food workers and performed serological and cellular response analyses of asymptomatic subjects in Wuhan, the original epicenter of the COVID-19 outbreak. Our data showed that up to 5.91% of the food workers carried SARS-CoV-2 IgG antibodies asymptomatically; however, in 90.4% of them, the antibody level declined over a 2-week period. IgM and IgG antibodies, including neutralizing antibodies, were significantly lower in asymptomatic subjects than in recovered symptomatic patients with similar disease courses. Furthermore, the asymptomatic subjects showed lymphopenia and a prominent decrease in the B-cell population, as well as a low frequency of antibody-secreting cells and a low cytokine response. These factors probably contributed to the low and unsustained antibody levels in asymptomatic subjects. Our results show that asymptomatic subjects are likely to be vulnerable to SARS-CoV-2 reinfection, and neither the proportion of population immunity nor the breadth of immune responses is sufficient for herd immunity.

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

We appreciate the thoughtful comments of H-J. Yang and co-workers in their correspondence addressing the predictors of mortality for patients with coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Their comments are very helpful to improve the expression and increase the quality of our paper [1]., Author response to the correspondence regarding “Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study” https://bit.ly/31X8cal

Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.

Since the outbreak of coronavirus disease 2019 (COVID-19) in China in December 2019, considerable attention has been focused on its elucidation. However, it is also important for clinicians and epidemiologists to differentiate COVID-19 from other respiratory infectious diseases such as influenza viruses.The aim of this study was to explore the different clinical presentations between COVID-19 and influenza A (H1N1) pneumonia in patients with ARDS.This analysis was a retrospective case-control study. Two independent cohorts of patients with ARDS infected with either COVID-19 (n = 73) or H1N1 (n = 75) were compared. Their clinical manifestations, imaging characteristics, treatments, and prognosis were analyzed and compared.The median age of patients with COVID-19 was higher than that of patients with H1N1, and there was a higher proportion of male subjects among the H1N1 cohort (P .05). Patients with COVID-19 exhibited higher proportions of nonproductive coughs, fatigue, and GI symptoms than those of patients with H1N1 (P .05). Patients with H1N1 had higher Sequential Organ Failure Assessment (SOFA) scores than patients with COVID-19 (P .05). The PaoThere were many differences in clinical presentations between patients with ARDS infected with either COVID-19 or H1N1. Compared with H1N1 patients, patients with COVID-19-induced ARDS had lower severity of illness scores at presentation and lower SOFA score-adjusted mortality.

Following acute infection, individuals COVID-19 may still shed SARS-CoV-2 RNA. However, limited information is available regarding the active shedding period or whether infectious virus is also shed. Here, we monitored the clinical characteristics and virological features of 38 patients with COVID-19 (long-term carriers) who recovered from the acute disease, but still shed viral RNA for over 3 months. The median carrying history of the long-term carriers was 92 days after the first admission, and the longest carrying history was 118 days. Negative-positive viral RNA-shedding fluctuations were observed. Long-term carriers were mostly elderly people with a history of mild infection. Infectious SARS-CoV-2 was isolated from the sputum, where high level viral RNA was found. All nine full-length genomes of samples obtained in March–April 2020 matched early viral clades circulating in January–February 2020, suggesting that these patients persistently carried SARS-CoV-2 and were not re-infected. IgM and IgG antibodies and neutralizing-antibody profiles were similar between long-term carriers and recovered patients with similar disease courses. In summary, although patients with COVID-19 generated neutralizing antibodies, they may still shed infectious SARS-CoV-2 for over 3 months. These data imply that patients should be monitored after discharge to control future outbreaks.

Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance (1H NMR) based metabolomics analysis disclosed that HSW could relieve stroke rats suffering from the ischemia/reperfusion injury by ameliorating the disturbed energy and amino acids metabolisms, alleviating the oxidative stress from reactive oxygen species and reducing the inflammation. HSW treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 signaling pathway, and exert anti-inflammatory effect by decreasing the levels of inflammatory factors such as cyclooxygenase-2, interleukin-1β, interleukin-6 and tumor necrosis factor-α. The integrated metabolomics approach showed its potential in understanding mechanisms of HSW in relieving ischemic stroke. Further study to develop HSW as an effective therapeutic agent to treat ischemic stroke is warranted.

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146‒17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755‒8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132‒14.006; p−1 (OR 4.077, 95% CI 1.166‒14.253; p+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1. The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.

Stroke is the third most common cause of death in most industrialized countries. Polygonum multiflorum (He-Shou-Wu, HSW) is one of the traditional Chinese medicines with multiple pharmacological activities which is widely used in Chinese recipe. This study aims to explore the protective effect of HSW on ischemic stroke rat model and to elucidate the underlying mechanisms. The mortality rate, neurological deficit, cerebral infarct size, histopathology, immunohistochemistry, biochemical parameters, quantitative real-time polymerase chain reaction and western blotting were used to access the treatment effects of HSW on ischemic stroke. Proton nuclear magnetic resonance (

ObjectivesDeterioration of cardiac performance under stress may be partly mediated by dysfunctional mitochondria and endoplasmic reticulum (ER) that is likely related to an activation of NADPH oxidase (NOX) and an increase in pro-inflammatory factors. We investigated if a new compound CPUY11018 (CPUY) derived from Azimilide could ameliorate the stress impaired cardiac performance.MethodsForty-eight male Sprague Dawley rats were randomly divided into six groups and were injected with isoproterenol (ISO, 1 ml/kg, s.c.) for 10 days. Cardiac myocytes and fibroblasts from neonate rats were incubated with ISO. CPUY was employed and compared with apocynin (APO) – an inhibitor of NOX.Key findingsIn ISO-treated group, the compromised haemodynamics and cardiac remodelling were significant with dysfunctional mitochondria indicated by decreased MnSOD and mitochondrial membrane potential, and an enhanced reactive oxygen species genesis. Downregulation of FKBP12.6, CASQ2 and SERCA2a was also remarkable in vivo and in vitro implying an abnormal ER. Upregulated Nox4, p22phox and p47phox were significant, associated with upregulation of Src, IκBβ and NFκB, and downregulation of pAMPK/AMPK and Cx40 in vivo and in vitro. These abnormalities were relieved by CPUY and APO.ConclusionsCPUY is potential in managing cardiac insufficiency through normalizing mitochondria and ER in the affected heart.

Objective To develop alternative therapeutic strategy that reduces hypercholesterolemia, inflammation and atherosclerosis, we investigate if fumigaclavine C (FC), an indole alkaloid in structure, has anti-atherosclerosis function, and if so, what is the mechanism involved. Methods and results We used ApoE-deficient (ApoE −/− ) mice as an atherosclerosis model to examine if FC reduced aorta lesion size and improved serum lipid profiles. ApoE −/− mice at 6 weeks of age were fed on a western diet for 10 weeks before FC was administrated (5, 10 and 20 mg/kg) by gavage daily for additional 4 weeks. The mice were sacrificed at 20 weeks of age for examination. The atherosclerotic lesions were assessed with Oil Red O staining in the whole aorta and aortic sinus. Serum levels of triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) were determined enzymatically. Mouse macrophages were examined for lipid droplets inside cells. FC's effect on PPARγ and PPARγ signaling pathway were further investigated by western blot and luciferase assay. We found that FC decreased atherosclerotic lesion formation in ApoE −/− mice in a dose-dependent manner. Also FC improved lipid profiles in ApoE −/− mice and reduced the foam cell numbers of peritoneal macrophages. FC stimulated PPARγ signaling pathway proteins both in vitro and in vivo. FC enhanced PPARγ transactivation activity assayed by a PPRE reporter system. Conclusion Our data indicated that FC activated PPARγ signaling pathway as well as its downstream proteins and had an effective role of anti-atherosclerosis.

Inflammatory changes in the cerebral network are present in early mechanisms involved in neurodegenerative disease, Alzheimer disease (AD), and aging brain. We intended to verify that these are likely due to an activation of NADPH oxidase (NOX) and endoplasmic reticulum (ER) stress. Apocynin (APO) an inhibitor of NOX is potential to ameliorate these changes. Rehmannia complex (Reh) a famous prescription in China and the triterpene acids (TTA) isolated from Reh may relieve the isoproterenol (ISO) induced chronic inflammation in the brain, compared with APO. Rats were administered with ISO for 10 days and astrocytes were incubated with ISO for 24 h. Changes in neural MMP (matrix metalloproteinase), Cx43, AQP4 (aquaporin 4), NFκB, IκBβ, and p-PERK (PKB like kinase) were conducted and intervened with APO, Reh and TTA, in vivo and in vitro, respectively. An increased MDA and upregulated NOX subunit p47phox, ETA, PERK in association with abnormal MMP-2/9 and Cx40/43 were found in cerebral tissue of ISO-injected rats. Astrocytes incubated with ISO exhibited upregulated APQ4, IκBβ, NFκB and p-PERK/PERK and downregulated Cx43. These were significantly abrogated by APO and Reh, in vivo, and APO and TTA in vitro. In conclusion, neural damages induced by ISO were characterized by inflammatory changes in cerebral tissue and astrocytes, which were blunted significantly by APO, Reh and TTA, respectively. Reh and TTA are potential in alleviating the early pathogenesis in neurodegenerative changes in AD in the clinical settings through suppressing NOX and ER stress in the brain.

IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown.To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space.The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed.Th22 cells were significantly higher in TPE than in blood. IL-1β, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen.The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation.

Trichothecin, one of fungal toxins which were encountered in food and in the environment, seriously threatens human and animal health. It has been shown that trichothecin changed the morphology of cellular mitochondria. However, the molecular mechanism remains unknown. Here we found that cell viability was attenuated by trichothecin. Features of apoptosis such as homosomal condensation and inter nucleosomal fragmentation were observed. In consistence with the elevated apoptosis rate, expression of anti-apoptotic protein Bcl-2 was diminished and expression of proapoptotic protein Bax was enhanced at mRNA levels. Furthermore, expression of caspase-9 and activity of caspase-3 were increased after the treatment of trichothecin. Accordingly, the mitochondrial membrane potential (∆Ψm) was decreased in a dose-dependent manner. And Ca2+ overload was induced by trichothecin, followed by the generation of reactive oxygen species (ROS). Collectedly, our results suggested that apoptosis induced by trichothecin is mediated by caspase-9 activation and the decrement of mitochondrial function resulted from the overloaded calcium and ROS production.

Both T helper interleukin 17 (IL-17)-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in human tuberculous pleural effusion (TPE); however, the possible interaction between Th17 cells and Tregs in TPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as the mechanism of Tregs in regulating generation and differentiation of Th17 cells in TPE. In the present study, the numbers of Th17 cells and Tregs in TPE and blood were determined by flow cytometry. The regulation and mechanism of CD39+Tregs on generation and differentiation of Th17 cells were explored. Our data demonstrated that the numbers of Th17 cells and CD39+Tregs were both increased in TPE compared with blood. Th17 cell numbers were correlated negatively with Tregs in TPE but not in blood. When naïve CD4+T cells were cultured with CD39+Tregs, Th17 cell numbers decreased as CD39+Treg numbers increased, and the addition of the anti-latency-associated peptide monoclonal antibody to the coculture reversed the inhibitory effect exerted by CD39+Tregs. This study shows that Th17/Treg imbalance exists in TPE and that pleural CD39+Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.

Impaired endothelial cell (EC) function leads to alterations in the permeability of the blood–brain barrier (BBB). There are two aspects of the transport through the BBB: from the blood to the brain (influx) and from the brain to the blood (efflux). An impaired EC model induced by L-thyroxine that compromises the influx and efflux properties of the BBB was used to assess responses to the intervention of CPU-86017 (an antioxidant and calcium channel blocker) and propranolol. CPU-86017 (t1/2=1.5 h) was also used as a target drug, leaving no traces in the brain and blood 24 h after administration. The permeability of the BBB was evaluated by using CPU-86017 after iv and icv injection and concentrations in the blood and brain being measured by high-performance liquid chromatography. The bidirectional permeability of CPU-86017 was impaired and associated with a reduced NO bioavailability assessed functionally by the vasoactivity in the model. Partial relief of NO bioavailability and oxidative stress induced by propranolol was consistent with a recovery of BBB efflux alone. Complete recovery in the efflux and influx of the BBB by CPU-86017 was a result of the complete restoration of NO bioavailability and reduction in oxidative stress. Normal BBB influx is dependent on an intact endothelial NO system, and efflux could be restored easily by partial improvement of NO bioavailability. CPU-86017 is thus more effective than propranolol in protecting the endothelium from damage produced by L-thyroxine through oxidative stress. Drug Dev. Res. 64:145–156, 2005. © 2005 Wiley-Liss, Inc.

The aim of this study was to investigate the distributions and relevance of Th1 and Th17 cells (IL-17-producing CD(+)(4) T cell), and the differentiation of Th17 cells in tuberculous pleural effusion.The percentages of both Th1 and Th17 cells in tuberculous pleural effusion and peripheral blood from 30 patients [male/female 12/18, age 16 - 63 years (average 41.2 year)] with tuberculous pleurisy were determined by flow cytometry, and comparison was made using Student's t test. The regulations of different combinations of IFN-γ, IL-1β, IL-6 and IL-12 on differentiation of Th17 cells were explored. Comparisons of the data between different groups were performed using Kruskal-Wallis one-way analysis of variance on ranks.Both Th1 [(39 ± 11)% vs (8 ± 3)%; t = 17.37, P0.05] and Th17 cells [(2.8 ± 0.9)% vs (0.7 ± 0.3)%; t = 14.78, P0.05] were significantly increased in tuberculous pleural effusion compared with peripheral blood. The proportions of Th17 cells were correlated positively with those of Th1 cells both in tuberculous pleural effusion and in peripheral blood (r = 0.61, 0.49, respectively; both P0.05). IL-1β or IL-6 promoted the differentiation of Th17 cells, and their combination resulted in further increase of the differentiation of Th17 cells, while IFN-γ and IL-12 reduced the percentages of Th17 cells. Moreover, these two cytokines significantly impaired the promotive effect induced by IL-1β plus IL-6.This study showed that Th1/Th17 balance existed in tuberculous pleural effusion, and was mainly due to the generation and differentiation of Th17 cells induced by IL-1β and IL-6, but reversed by IFN-γ and IL-12 in tuberculous pleural effusion.

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.

Newly discovered IL-9-producing CD4(+) helper T cells (Th9 cells) have been reported to contribute to tissue inflammation and immune responses, however, differentiation and immune regulation of Th9 cells in tuberculosis remain unknown. In the present study, our data showed that increased Th9 cells with the phenotype of effector memory cells were found to be in tuberculous pleural effusion as compared with blood. TGF-β was essential for Th9 cell differentiation from naïve CD4(+) T cells stimulated with PMA and ionomycin in vitro for 5 h, and addition of IL-1β, IL-4 or IL-6 further augmented Th9 cell differentiation. Tuberculous pleural effusion and supernatants of cultured pleural mesothelial cells were chemotactic for Th9 cells, and this activity was partly blocked by anti-CCL20 antibody. IL-9 promoted the pleural mesothelial cell repairing and inhibited IFN-γ-induced pleural mesothelial cell apoptosis. Moreover, pleural mesothelial cells promoted Th9 cell differentiation by presenting antigen. Collectively, these data provide new information concerning Th9 cells, in particular the collaborative immune regulation between Th9 cells and pleural mesothelial cells in human M. tuberculosis infection. In particular, pleural mesothelial cells were able to function as antigen-presenting cells to stimulate Th9 cell differentiation.

Aims Atherosclerosis is the main cause of cardiovascular disease and is widely treated with statins. However, there are a few cases of intolerable adverse reactions by statins; thus, there is still a need for new drugs to prevent atherosclerosis. The inflammation associated with the activation of Toll-like receptor 4 (TLR4) and nuclear factor κB (NFκB) has been shown to be an important factor in the development of atherosclerosis. In the current study, we investigated the anti-inflammatory action of the fungal alkaloid fumigaclavine C (FC), its effects on the TLR4 and NFκB signaling pathway, and its potential relevance as an anti-atherosclerotic agent. Main methods The inhibitory effects of FC on tumor necrosis factor α (TNFα) production were determined by enzyme-linked immunosorbent assays (ELISA). The mRNA and protein expression of TLR4 and p65NFκB were detected by quantitative real-time polymerase chain reaction and western blot analysis, respectively. The effect of FC on NFκB was determined using the Dual-Luciferase reporter assay. Key findings FC reduced TNFα production in LPS-stimulated human whole blood and RAW 264.7 macrophages via reduced IκBα phosphorylation associated with the decreased expression of p65NFκB. FC also suppressed LPS-induced TLR4 overexpression at the mRNA and protein level. Significance FC attenuated TNFα via the TLR4-NFκB signaling transduction pathway, suggesting that this alkaloid might serve as a promising molecule for anti-inflammatory treatment of atherosclerosis.

The aim of this study was to verify whether exaggerated arrhythmogenesis is attributed to inflammatory factors actively involving an excess of reactive oxygen species (ROS), transforming growth factor (TGF)-β and endothelin (ET). We hypothesized that CPU86017, derived from berberine, which possesses multi-channel blocking activity, could suppress inflammatory factors, resulting in inhibition of over-expression of ether-a-go-go (ERG) and an augmented incidence of ventricular fibrillation (VF) in ischaemia/reperfusion (I/R). Rats with cardiomyopathy (CMP) induced by thyroxine (0.2 mg−1kg−1 s.c. daily for 10 days) were treated with propranolol (10 mg kg−1 p.o.) or CPU86017 (80 mg kg−1 p.o.) on days 6–10. On the 11th day, arrhythmogenesis of the CMP was evaluated by I/R. In the CMP control group, an increase in VF incidence was found with the I/R episode, accompanied by increased ROS, which manifested as an increased level of malondialdehyde and decreased activities of SOD, glutathione peroxidase and catalase in the myocardium. Levels of inducible nitric oxide synthase and TGF-β mRNA were increased in association with upregulation of preproET-1 and ET- converting enzyme. We found increased levels of ERG, which correlated well with arrhythmogenesis. Treatment with CPU86017 or propranolol reversed these changes. These experiments verified our hypothesis that the inflammatory factors ROS, iNOS, TGF-β and ET-1 are actively involved in upregulation of ERG and arrhythmogenesis. CPU86017 and propranolol reduced VF by suppressing these inflammatory factors in the myocardium.

To evaluate the therapeutic effect of a short course chemotherapy on initially sputum positive cavitary pulmonary tuberculosis or tuberculoma by bacteriological examination of specimens through percutaneous lung biopsy after the chemotherapy.Eighty-three cases of initially sputum positive pulmonary tuberculosis with cavities or tuberculoma were included from Jan. 2002 and May. 2004. The patients finished a course of chemotherapy (2HREZ/4HR), and the sputum was converted to smear-negative and culture-negative, but cavities or tuberculoma remained on the chest X-ray. Lung specimens were obtained from the wall or content of the cavity or from the tuberculoma by CT-guided percutaneous lung biopsy for bacteriological examination within one month after the course.All the needle biopsy specimens were smeared and cultured for Mycobacterium tuberculosis. Eight cases (8/83, 9.6%) showed positive results: 3 were smear-positive and culture-positive, and 5 smear-negative but culture-positive. Drug susceptibility test showed that 7 of them were drug-sensitive and the remaining 1 was resistant to rifampin and isoniazid. After follow-up of 24 months, 6 of them converted to sputum smear-positive.Our study showed that 90.4% (75/83) of the tuberculosis cases achieved real bacteriological negative result on biopsies after a short course chemotherapy, and the bacteriological positive cases on biopsy experienced 75.0% (6/8) sputum bacteriological recurrence. The result suggests that the evaluation criteria with sputum on therapeutic effect of pulmonary tuberculosis needs to be reassessed.