Background Abelmoschus manihot , a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess ...its efficacy and safety in patients with primary glomerular disease. Study Design Prospective, open-label, multicenter, randomized, controlled, clinical trial. Setting & Participants From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. Interventions A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. Outcomes & Measurements The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Results Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot , losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2 , respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups ( P > 0.05), and there were no severe adverse events in any group. Limitations Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. Conclusions A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.
Background C/EBP homologous protein (Chop), a marker of endoplasmic reticulum (ER) stress, exhibits aberrant expression patterns during asthma development. However, its exact role in asthma ...pathogenesis is not fully understood. Objectives We aimed to determine the function and mechanism of Chop in the pathogenesis of allergic asthma in patients and animals. Methods Studies were conducted in asthmatic patients and Chop−/− mice to dissect the role of Chop and ER stress in asthma pathogenesis. An ovalbumin (OVA)–induced allergic airway inflammation model was used to address the effect of Chop deficiency on asthma development. Next, the effect of Chop deficiency on macrophage polarization and related signaling pathways was investigated to demonstrate the underlying mechanisms. Results Asthmatic patients and mice after OVA induction exhibited aberrant Chop expression along with ER stress. Specifically, Chop was noted to be specifically overexpressed in macrophages, and mice deficient in Chop were protected from OVA-induced allergic airway inflammation, as manifested by attenuated airway inflammation, remodeling, and hyperresponsiveness. Chop was found to exacerbate allergic airway inflammation by enhancing M2 programming in macrophages. Mechanistic studies characterized an IL-4/signal transducer and activator of transcription 6/transcription factor EC (Tfec)/IL-4 receptor α positive feedback regulatory loop, in which IL-4 induces Chop expression, which then promotes signal transducer and activator of transcription 6 signaling to transcribe Tfec expression. Finally, Tfec transcribes IL-4 receptor α expression to promote M2 programming in macrophages. Conclusions Chop and ER stress are implicated in asthma pathogenesis, which involves regulation of M2 programming in macrophages.
Background
We aimed to investigate the determinant factors of anti-PD-1 therapy outcome in nasopharyngeal carcinoma (NPC).
Methods
In this retrospective study, we included 64 patients with ...recurrent/metastatic NPC. The association of patients’ characteristics, C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and lactate dehydrogenase (LDH) with survival benefit of anti-PD-1 therapy were analyzed using Cox regression models and Kaplan-Meier analyses. Patients were divided based on the median value of CRP, NLR or LDH into different subgroups.
Results
At a median follow-up time of 11.4 months (range: 1-28 months), median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% CI, .18-3.6) and 15 months (95% CI, 10.9-19.1) months, respectively. Pretreatment metastases numbers was significant predictor of PFS (HR = 1.99; 95% CI 1.10-3.63; P = .024) and OS (HR = 2.77; 95% CI 1.36-5.61; P = .005). Baseline LDH level was independent predictor of OS (HR = 7.01; 95% CI 3.09-15.88; P < .001). Patients with LDH level >435 U/L at the baseline had significantly shorter PFS and OS compared to patients with LDH level ≤435 U/L (median PFS: 1.7 vs 3.5 months, P = .040; median OS: 3.7 vs 18.5 months, P < .001). Patients with non-durable clinical benefit (NDB) had significantly higher LDH level at the baseline compared to patients who achieved durable clinical benefit (DCB) (P = .025). Post-treatment levels of CRP, LDH, and NLR were decreased compared to baseline in patients with DCB (P = .030, P = .088, and P = .066, respectively), whereas, there was a significant increase in post-treatment level of LDH compared with baseline in patients with NDB (P = .024).
Conclusions
LDH level at the baseline was an independent predictor of OS and pretreatment metastases numbers was a significant predictor of PFS and OS.
Objectives The aim of this study was to define the genetic basis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Background Arrhythmogenic right ventricular cardiomyopathy, characterized ...by right ventricular fibrofatty replacement and arrhythmias, causes sudden death. Autosomal dominant inheritance, reduced penetrance, and 7 desmosome-encoding causative genes are known. The basis of low penetrance is poorly understood. Methods Arrhythmogenic right ventricular cardiomyopathy probands and family members were enrolled, blood was obtained, lymphoblastoid cell lines were immortalized, deoxyribonucleic acid was extracted, polymerase chain reaction (PCR) amplification of desmosome-encoding genes was performed, PCR products were sequenced, and diseased tissue samples were studied for intercellular junction protein distribution with confocal immunofluorescence microscopy and antibodies against key proteins. Results We identified 21 variants in plakophilin-2 ( PKP2 ) in 38 of 198 probands (19%), including missense, nonsense, splice site, and deletion/insertion mutations. Pedigrees showed wide intra-familial variability (severe early-onset disease to asymptomatic individuals). In 9 of 38 probands, PKP2 variants were identified that were encoded in trans (compound heterozygosity). The 38 probands hosting PKP2 variants were screened for other desmosomal genes mutations; second variants (digenic heterozygosity) were identified in 16 of 38 subjects with PKP2 variants (42%), including desmoplakin ( DSP ) (n = 6), desmoglein-2 ( DSG2 ) (n = 5), plakophilin-4 ( PKP4 ) (n = 1), and desmocollin-2 ( DSC2 ) (n = 1). Heterozygous mutations in non -PKP 2 desmosomal genes occurred in 14 of 198 subjects (7%), including DSP (n = 4), DSG2 (n = 5), DSC2 (n = 3), and junctional plakoglobin ( JUP ) (n = 2). All variants occurred in conserved regions; none was identified in 700 ethnic-matched control subjects. Immunohistochemical analysis demonstrated abnormalities of protein architecture. Conclusions These data suggest that the genetic basis of ARVC includes reduced penetrance with compound and digenic heterozygosity. Disturbed junctional cytoarchitecture in subjects with desmosomal mutations confirms that ARVC is a disease of the desmosome and cell junction.
Integrative oncology has developed for about 20 years in some countries; however, integrative oncology is still a relative new term for most China’s oncologists. Thus, it is essential to summarize ...the experience and expertise, share details of differing existing models and discuss future perspectives to help define and guide practice in integrative oncology in China. This study presents a summary of the basic characteristics, status, and challenges of integrative oncology in China, and also reports on China’s integrative physicians’ service delivery, clinical practice and research patterns of integrative oncology by an online national survey, including 405 oncologists. It is easy for cancer patients to access to integrative therapies in China. Public funding is sufficient for integrative oncology in China, and services are often provided through general hospitals and academic hospitals. Most (95.3%) of oncologists showed a positive attitude toward the development of integrative oncology. More than half (55.6%) of the oncologists worried about the influence on integrative oncology of COVID-19, especially for routine treatment, follow-up and holding seminars. We found that integrative oncology in China has swiftly developed in recent years. However, we suggest that standard diagnosis and treatment patterns and national professional guidelines should be set up as soon as possible.
Abstract Background and purpose Periostin, a matricellular protein, plays an important role in cardiac development and remodeling. Its expression profile and the association with myocardial fibrosis ...have not been investigated in human failing hearts. This work aimed to explore the behavior and pathologic significance of periostin in signifying collagen fibrogenesis in human hearts from patients with end-stage heart failure. Methods and subjects Tissues were collected from heart transplant recipients and the control hearts were from unmatched donors. Periostin mRNA and protein were detected using quantitative real-time polymerase chain reaction and Western blotting. Immunohistochemistry staining was employed to directly detect the protein level and distribution of periostin in heart tissues. The extent of myocardial fibrosis was expressed by the percentage of Masson's trichrome staining. Gelatin zymography was used to detect the activities of matrix metalloproteinase (MMP)2 and MMP9. Results A low level of periostin mRNA expression was found in control hearts while not detectable at the protein level. Periostin mRNA was increased significantly in failing myocardium compared to that of controls. Periostin was distributed extensively in left ventricle and interventricular septum of the failing hearts. Correlation analysis showed periostin protein expression was positively associated with myocardial fibrosis as well as left ventricular diastolic dimension. The distribution and extent of periostin was consistent with that of myocardial fibrosis. MMP2 activity has an obvious increase about fourfold in heart tissues from HF patients. But there is no quantitative association with the expression of periostin. Conclusions Periostin, the distribution and expression of which were consistent with the extent of myocardial fibrosis, might be a potential biomarker of cardiac remodeling in heart failure patients.
Abstract Objectives This study sought to investigate long-term clinical outcomes following coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with ...unprotected left main disease (ULMD). Background PCI has been increasingly used as an alternative mode of revascularization for ULMD. However, there are limited data comparing clinical outcomes between CABG surgery and PCI. Methods Between 2004 and 2010, 4,046 consecutive patients with ULMD were treated with either CABG surgery (n = 2,604) or PCI (n = 1,442) with drug-eluting stents. The primary outcome was 3-year all-cause mortality and the secondary outcome was the composite of death, nonfatal myocardial infarction, or nonfatal stroke. Results The unadjusted 3-year all-cause mortality was higher in the PCI group as compared with the CABG group (3.8% vs. 2.5%; log-rank p = 0.03), although there was no significant difference in the composite outcome (7.5% vs. 9.4%; log-rank p = 0.07). After adjustment for differences in baseline risk factors, PCI was associated with significantly higher risk of all-cause mortality (hazard ratio HR: 1.71; 95% confidence interval CI: 1.32 to 2.21; p < 0.001) but similar risk of the composite outcome (HR: 0.94; 95% CI: 0.82 to 1.09; p = 0.43). These differences were not statistically significant among patients with low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (≤32) or diabetes; however, PCI was associated with an increased risk among those with high SYNTAX score (>32), with HRs of 3.10 (95% CI: 1.84 to 5.22; p < 0.001) for all-cause mortality and 1.82 (95% CI: 1.36 to 2.45; p < 0.001) for the composite outcome. CABG was associated with lower risk of repeat revascularization but higher risk of stroke in each clinically relevant subgroup. Conclusions In this single-center observational study among patients with ULMD, CABG was associated with improved long-term outcomes, especially in patients with more complex disease.
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•DVDMS-SDT reduces neovascularization in late-stage atherosclerotic lesions in both rabbit and mouse models.•DVDMS-SDT enhances macrophage foam cell apoptosis, which in turn induces ...neovessel endothelial cell apoptosis and inhibits its proliferation, migration, and tubulogenesis, termed apoptosis-induced apoptosis.•Mechanistically, DVDMS-SDT induces macrophage foam cell apoptosis via mitochondrial-caspase pathway, which activates caspase 3 to cleave SP-1, leading to the reduction of HIF-1α and VEGF-A.•In the pilot translational study, DVDMS-SDT reduces plaque angiogenesis and inhibits vessel inflammation.
During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment.
Abstract Objective Few studies on suicidal ideation have been conducted in post-stroke patients in China. This national study examined suicidal ideation at 1-year post-stroke and explored its ...demographic and clinical correlates. Methods A total of 1418 patients with ischemic stroke were included in 56 hospitals nationwide. Demographic, clinical characteristics and neuro-imaging information were collected with standardized instruments, including assessment of stroke severity, depression, cognitive impairment, stroke recurrence, physical disability and insomnia. Suicidal ideation was measured using item 3 of the Hamilton Rating Scale for Depression. Results The frequency of suicidal ideation in this study was 6.6%. Multivariate analyses revealed that disability (OR = 2.07, 95% CI = 1.09–3.05), stroke recurrence (OR = 4.13, 95% CI = 1.74–9.77) and insomnia early (OR = 1.87, 95% CI = 1.03–3.39), middle (OR = 2.66, 95% CI = 1.46–4.85) and late (OR = 2.35, 95% CI = 1.31–4.19) at the 1-year follow-up and post-stroke depression (OR = 2.16, 95% CI = 1.23–3.82) were significantly associated with post-stroke suicidal ideation. Conclusion Post-stroke depression, disability, insomnia and stroke recurrence are possible risk factors of suicidal ideation that warrant attention in clinical practice.
Abstract Animal and imaging study evidence favors early reperfusion for acute myocardial infarction (AMI). However, in clinical trials the effect of symptom-onset-to-balloon (S2B) time on clinical ...outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) has been inconsistent. Moreover, there is few data regarding the ischemic time in China. A total of 3877 consecutive STEMI patients with available S2B time undergoing pPCI from January 2013 to September 2014 at 108 hospitals that participated in the China Acute Myocardial Infarction (CAMI) registry were included and stratified into three S2B groups: <6 h, 6-12 h, >12 h. S2B time was tested in multivariate logistic regression analyses as an independent risk factor of mortality (primary outcome), major adverse cardiovascular and cerebrovascular events (MACCE) and impaired myocardial perfusion (secondary outcomes). The median S2B time was 5.5 (3.75-8.50) hours. Longer S2B time was associated with higher in-hospital mortality (<6 h: 2.7%; 6-12 h: 3.4%; >12 h: 4.9%; P=0.047) and ST-segment resolution <50% (<6 h: 16.7%; 6-12 h: 19.2%; >12 h: 24.3%; P=0.002) but not MACCE. In multivariate adjusted analysis, S2B>12 h remained associated with ST-segment resolution<50% (OR=1.53, 95% CI 1.16-2.01, P=0.002), but not with in-hospital mortality (1.673 0.95-2.94, P=0.073). In conclusion, median S2B time in STEMI patients undergoing pPCI was longer than that in registry studies from other countries. Longer S2B time was associated with impaired myocardial perfusion but not with in-hospital mortality or MACCE.
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