Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Summary Background Several pioneering studies have provided evidence for the introduction of universal pulse oximetry screening for critical congenital heart disease. However, whether the benefits of ...screening reported in studies from high-income countries would translate with similar success to low-income countries is unknown. We assessed the feasibility and reliability of pulse oximetry plus clinical assessment for detection of major congenital heart disease, especially critical congenital heart disease, in China. Methods We did a pilot study at three hospitals in Shanghai to assess the accuracy of pulse oximetry plus clinical assessment for detection of congenital heart disease. We made a data collection plan before recruitment. We then undertook a large, prospective, and multicentre screening study in which we screened all consecutive newborn babies (aged 6–72 h) born at 18 hospitals in China between Aug 1, 2011, and Nov 30, 2012. Newborn babies with positive screen results (either an abnormal pulse oximetry or abnormal clinical assessment) were referred for echocardiography within 24 h of screening. We identified false-negative results by clinical follow-up and parents' feedback. We calculated sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios for pulse oximetry alone, and in combination with clinical assessment, for detection of major and critical congenital heart disease. Findings In the pilot study, 6785 consecutive newborn babies were screened; 46 of 49 (94%) cases of asymptomatic major congenital heart disease and eight of eight (100%) cases of asymptomatic critical disease were detected by pulse oximetry and clinical assessment. In the prospective multicentre study, we screened 122 738 consecutive newborn babies (120 707 asymptomatic and 2031 symptomatic), and detected congenital heart disease in 1071 (157 critical and 330 major). In asymptomatic newborn babies, the sensitivity of pulse oximetry plus clinical assessment was 93·2% (95% CI 87·9–96·2) for critical congenital heart disease and 90·2% (86·4–93·0) for major disease. The addition of pulse oximetry to clinical assessment improved sensitivity for detection of critical congenital heart disease from 77·4% (95% CI 70·0–83·4) to 93·2% (87·9–96·2). The false-positive rate for detection of critical disease was 2·7% (3298 of 120 392) for clinical assessment alone and 0·3% (394 of 120 561) for pulse oximetry alone. Interpretation Pulse oximetry plus clinical assessment is feasible and reliable for the detection of major congenital heart disease in newborn babies in China. This simple and accurate combined method should be used in maternity hospitals to screen for congenital heart disease. Funding Key Clinical Research Project sponsored by Ministry of Health, Shanghai Public Health Three-Year Action Plan sponsored by Shanghai Municipal Government, and National Basic Research Project of China.
Objective The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology ...clinics in large cities of China. Materials and Methods A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. Results In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. Conclusion The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients.
Background Intracranial arterial stenosis is a common cause of ischemic stroke in Asians. We therefore sought to explore the relationship of brachial-ankle pulse wave velocity and intracranial ...arterial stenosis in 834 stroke-free hypertensive patients. Methods Intracranial arterial stenosis was evaluated through computerized tomographic angiography. Brachial-ankle pulse wave velocity was measured by an automated cuff device. Results The top decile of brachial-ankle pulse wave velocity was significantly associated with intracranial arterial stenosis ( P = .027, odds ratio = 1.82; 95% confidence interval: 1.07-3.10). The patients with the top decile of brachial-ankle pulse wave velocity showed 56% higher risk for the presence of intracranial arterial stenosis to the whole population, which was more significant in patients younger than 65 years old. We also found that brachial-ankle pulse wave velocity related to both intracranial arterial stenosis and homocysteine. Conclusion Our study showed the association of brachial-ankle pulse wave velocity with asymptomatic intracranial arterial stenosis in hypertension patients, especially in relative younger subjects. Brachial-ankle pulse wave velocity might be a relatively simple and repeatable measurement to detect hypertension patients in high risk of intracranial arterial stenosis.
Background Since 2008, severe cases of emerging human adenovirus (HAdV) type 55 (HAdV-55) were reported sporadically in China. But no comparative studies had been conducted to discern the differences ...in epidemiologic and clinical abnormalities between HAdV-55 and other types (HAdV-7, HAdV-3, HAdV-14, HAdV-50, and HAdV-C). Methods A multicenter surveillance study for adult and adolescent community-acquired pneumonia (CAP) was conducted prospectively in Beijing and Yan Tai between November 2010 and April 2012. A standardized data form was used to record clinical information. The viral DNA extracted from the clinical samples or adenovirus viral isolates was sequenced. Results Among 969 cases, 48 (5%) were identified as adenovirus pneumonia. Six branches were clustered: HAdV-55 in 21, HAdV-7 in 11, HAdV-3 in nine, HAdV-14 in four, HAdV-50 in two, and HAdV-C in one. Most HAdV-55 cases were identified during February and March. All the hypervariable regions of the hexon genes of the 21 HAdV-55 strains were completely identical. Patients who had HAdV-55 were about 10 years older ( P = .027) and had higher pneumonia severity index scores ( P = .030) compared with those with other types (HAdV-7, HAdV-3, HAdV-14, HAdV-50, and HAdV-C). Systemic BP was also higher among patients in the HAdV-55 group ( P = .006). Unilateral or bilateral consolidations were the most common radiologic findings in both patients with HAdV-55 and those with other types (57.9% vs 36%). More than one-half of the patients were admitted to hospital; oxygen therapy was given to 29.2% of the 48 patients, and two needed mechanical ventilation. Conclusions HAdV-55 has established itself as a major pneumonia pathogen in the Chinese population, and further surveillance and monitoring of this agent as a cause of CAP is warranted.
Summary Background Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where ...there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community. Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, is an alternative to aspirin that works through a different mechanism. This trial aimed to compare the efficacy and safety of cilostazol with that of aspirin for the long-term prevention of the recurrence of ischaemic stroke. Methods 720 patients (mean age 60·2 years, SD 9·86) who had had an ischaemic stroke within the previous 1–6 months were enrolled consecutively in a prospective, multicentre, double-blind, randomised trial. 360 patients were randomly assigned to receive cilostazol and 360 patients to receive aspirin. Analysis was by intention to treat. Patients in both groups took the medication for 12–18 months. The primary endpoint was any recurrence of stroke (ischaemic stroke, haemorrhagic stroke, or subarachnoid haemorrhage) during the trial period. All patients had MRI with T1 MRI, T2 MRI, diffusion-weighted imaging (DWI), T2 fluid-attenuated inversion recovery (FLAIR), and T2 gradient echo imaging (T2*) at the beginning and the end of the study. This trial is registered with ClinicalTrials.gov , number NCT00202020. Findings The average duration of treatment was 740 person-years, and 719 patients were analysed (360 in the cilostazol group and 359 in the aspirin group). The primary endpoint was reported in 12 patients in the cilostazol group and in 20 patients in the aspirin group. The estimated hazard ratio, calculated with Kaplan–Meier curves (risk of primary endpoint in cilostazol group vs aspirin group), was 0·62 (95% CI 0·30–1·26; p=0·185). Symptomatic cerebral haemorrhage was reported in six patients: one in the cilostazol group and five in the aspirin group. Asymptomatic cerebral haematoma was found in four patients in the aspirin group and one patient in the cilostazol group. Brain bleeding events were significantly more common in the aspirin group than in the cilostazol group (7 vs 1, p=0·034). All of the six patients with symptomatic haemorrhage had previous cerebral microbleeds in the area where the haematoma was located. Interpretation The results of this pilot study showed no significant difference in the rate of recurrence of stroke between patients with ischaemic stroke who were randomly assigned to take either cilostazol or aspirin. The lower rates of ischaemic and haemorrhagic stroke in the cilostazol group suggest that cilostazol might be a more effective and safer alternative to aspirin for Chinese patients with ischaemic stroke; however, a larger phase III trial is required to confirm this. Funding National Health Ministry of the People's Republic of China; Otsuka Pharmaceutical.
Background In light of the burgeoning volume and certain variation of in-hospital outcomes of cardiac operations in China, a large patient-level registry was needed. We generated the Chinese Cardiac ...Surgery Registry (CCSR) database in 2013 to benchmark, continuously monitor, and provide feedback of the quality of adult cardiac operations. We report on the design of this database and provide an overview of participating sites and quality of data. Methods We established a network of participating sites with an adult cardiac surgery volume of more than 100 operations per year for continuous web-based registry of in-hospital and follow-up data of coronary artery bypass grafting (CABG) and valve operations. After a routine data quality audit, we report the performance and quality of care back to the participating sites. Results In total, 87 centers participated and submitted 46,303 surgical procedures from January 2013 to December 2014. The timeliness rates of the short-list and in-hospital data submitted were 73.6% and 70.2%, respectively. The completeness and accuracy rates of the in-hospital data were 97.6% and 95.1%, respectively. We have provided 2 reports for each site and 1 national report regarding the performance of isolated CABG and valve operations. Conclusions The newly launched CCSR with a national representativeness network and good data quality has the potential to act as an important platform for monitoring and improving cardiac surgical care in mainland China, as well as facilitating research projects, establishing benchmarking standards, and identifying potential areas for quality improvements ( ClinicalTrials.gov No. NCT02400125 ).
Abstract Purpose To compare a new swept source optical coherence tomography (SS-OCT) based biometer (OA-2000) with the IOLMaster v5.4 (partial coherence interferometry) and Aladdin (optical ...low-coherence interferometry) biometers in terms of axial length measurement and failure rate in eyes with cataract. Design Reliability study Methods A total of 377 eyes of 210 patients were scanned with the three biometers in a random order. For each biometer, the number of unobtainable axial length measurements was recorded and grouped as per the type and severity of cataract based on the Lens Opacities Classification System III by the same experienced ophthalmologist. The Bland-Altman limits of agreement (LoA) method was used to assess the agreement in axial length measurements between the three biometers. Results The failure rate was 0 eyes (0%) with the OA-2000, 136 eyes (36.07%) with the IOLMaster and 51 eyes (13.53%) with the Aladdin. Chi-squared analyses indicated a significant difference in failure rate between all three devices (P<0.001). Logistic regression analysis highlighted a statistically significant trend of higher failure rates with increasing severity of nuclear, cortical and posterior subcapsular cataracts. Bland-Altman statistics indicated small mean differences and narrow LoA (OA-2000 versus IOLMaster -0.09 to 0.08mm; OA-2000 versus Aladdin -0.10 to 0.07mm; IOLMaster versus Aladdin -0.05 to 0.04mm). Conclusions The OA-2000, a new SS-OCT based biometer, outperformed both the IOLMaster and Aladdin biometers in very advanced cataracts of various morphologies. The use of SS-OCT technology may be the reason for the improved performance of the OA-2000 and may lead to this technology becoming the gold standard for the measurement of axial length.
Abstract Background Interferon alpha-inducible protein 27 (IFI27) is an interferon alpha-inducible protein, which was found to be upregulated in some cancers, such as breast cancer, squamous cell ...carcinoma, hepatocellular carcinoma, and serous ovarian carcinoma. However, the role of IFI27 in ovarian cancer remains to be elucidated. This study was designed to investigate the role of IFI27 in ovarian cancer tumorigenicity. Materials and methods The expression of IFI27 was examined in ovarian cancer tissues and cell lines by real time quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The cell migration and invasion was investigated by wound healing and transwell invasion assay. The epithelial–mesenchymal transition markers were detected by Western blotting and the stemness was evaluated by sphere formation. The tumor growth was examined in the athymic mice model. Results We found that IFI27 is overexpressed in ovarian cancer and associated with patients' survival. Interestingly, we further observed that the expression of IFI27 was associated with the expression of mesenchymal marker vimentin in ovarian cancer. Overexpression of IFI27 induces epithelial–mesenchymal transition and promotes epithelial ovarian cancer cells migration and invasion, tumorigenicity, stemness, and drug resistance. Moreover, overexpression of IFI27 is associated with loss of miR-502 in ovarian cancer. Reexpression of miR-502 inhibits IFI27-induced tumorigenicity, migration, and drug resistance. Conclusions These data suggested that IFI27 may be a potential target for developing novel diagnosis strategies and therapeutic interventions.
Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase ...2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications.
Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded.
All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively.
Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.
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