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.
Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
Objectives This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney ...disease (CKD). Background CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes TRACK-D; NCT00786136 )
To investigate the current situation of neonatal care resources (NCR), newborn mortality rates (NMR), regional differences and existing challenges in China.
By using a self-designed questionnaire ...form and the cross-sectional method, we conducted a survey of all hospitals equipped with neonatal facilities in China from March 2019 to March 2020 with respect to the level and nature of these hospitals, the number of newborn beds and NICU beds, the number of neonatal pediatricians, and the development of therapeutic techniques. The data about the newborn births and deaths were retrieved from the annual statistics of the health commissions of the related provinces, autonomous regions and municipalities.
Included in this nationwide survey were 3,020 hospitals from all 22 provinces, 5 autonomous regions and 4 municipalities directly under the Central Government of Mainland China, with a 100% response rate. They included 1,183 (39.2%) level-3 (L3) hospitals, 1629 (53.9%) L-2 hospitals and 208 (6.9%) L-1 hospitals. Geographically, 848 (31.4%) hospitals were distributed in Central China, 983 (32.5%) hospitals in East China, and 1,089 (36.1%) in West China. The 3,020 included hospitals were altogether equipped with 75,679 newborn beds, with a median of 20 (2-350) beds, of which 2,286 hospitals (75.7%) were equipped with neonatal intensive care units (NICU), totaling 28,076 NICU beds with a median of 5 (1-160) beds. There were altogether 27,698 neonatal pediatricians in these hospitals, with an overall doctor-bed ratio of 0.366. There were 48.18 newborn beds and 17.87 NICU beds per 10,000 new births in China. In East, Central and West China, the number of neonatal beds, NICU beds, neonatal pediatricians, and attending pediatricians or pediatricians with higher professional titles per 10,000 newborns was 42.57, 48.64 and 55.67; 17.07, 18.66 and 18.17; 16.26, 16.51 and 20.81; and 10.69, 10.81 and 11.29, respectively. However, when the population and area are taken into consideration and according to the health resources density index (HRDI), the number of newborn beds, NICU beds and neonatal pediatricians in West China was significantly lower than that in Central and East China. In addition, only 10.64% of the neonatal pediatricians in West China possessed the Master or higher degrees, vs. 31.7% in East China and 20.14% in Central China. On the contrary, the number of neonatal pediatricians with a lower than Bachelor degree in West China was significantly higher than that in Central and East China (13.28% vs. 7.36% and 4.28%). Technically, the application rate of continuous positive airway pressure (CPAP) and conventional mechanical ventilation (CMV) in L-1 hospitals of West China was lower than that in Central and East China. According to the statistics in 2018, the newborn mortality rate (NMR) in West China was significantly higher than that in Central and East China.
China has already possessed relatively good resources for neonatal care and treatment, which is the primary reason for the rapid decrease in the NMR in China. However, there are still substantial regional differences. The density of health resources, the level of technical development and educational background of neonatal pediatricians in West China still lag behind those in other regions of China and need to be further improved and upgraded.
This research work was funded by National Natural Science Foundation of China (81671504) and United Nations International Children's Emergency Fund (CHINA-UNICEF501MCH).
Background The efficacy of tonsillectomy in immunoglobulin A nephropathy (IgAN) remains controversial. Our meta-analysis was intended to investigate its efficacy as an adjunct or independent ...treatment. Study Design Meta-analysis of prospective and retrospective studies using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Setting & Population Patients with IgAN treated with or without tonsillectomy. Selection Criteria for Studies Studies that compared clinical remission or end-stage renal disease (ESRD) in patients with IgAN with or without tonsillectomy. Intervention Tonsillectomy. Outcomes Clinical remission and ESRD. Results 14 studies (1,794 patients) were included and a random-effects model was applied. There were significantly greater odds of clinical remission with tonsillectomy (10 studies, 1,431 patients; pooled OR, 3.40; 95% CI, 2.58-4.48; P < 0.001). Sensitivity analysis to exclude the effects of renin-angiotensin system inhibitors yielded consistent results (6 studies, 671 patients; pooled OR for remission, 2.80; 95% CI, 1.91-4.09; P < 0.001). In subgroup analysis of the remission outcome, tonsillectomy plus steroid pulse therapy was superior to steroid pulse therapy alone (7 studies, 783 patients; pooled OR, 3.15; 95% CI, 1.99-5.01; P < 0.001), and tonsillectomy plus conventional steroid therapy was superior to conventional steroid therapy alone (2 studies, 159 patients; pooled OR, 4.13; 95% CI, 1.23-13.94; P = 0.02). Tonsillectomy was superior to general treatment (3 studies, 187 patients; pooled OR for remission, 2.21; 95% CI, 1.20-4.05; P = 0.01). In addition, tonsillectomy was associated with decreased odds of ESRD (9 studies, 873 patients; pooled OR, 0.25; 95% CI, 0.12-0.52; P < 0.001). 2 sensitivity analyses, one excluding studies with less than 5 years’ follow-up and another excluding the confounding effect of renin-angiotensin system inhibitors, yielded nearly the same reduction in ESRD risk (6 studies, 691 patients; pooled OR, 0.20; 95% CI, 0.11-0.36; P < 0.001; and 6 studies, 547 patients; pooled OR, 0.24; 95% CI, 0.14-0.44; P < 0.001). Limitations Most included studies were retrospective cohort studies; we were unable to adjust uniformly for potential confounding variables. Conclusions As adjunct or independent therapy, tonsillectomy may induce clinical remission and reduce the rates of ESRD in patients with IgAN.
Summary Background China has achieved Millennium Development Goal 4 to reduce under-5 mortality rate by two-thirds between 1990 and 2015. In this study, we estimated the national and subnational ...levels and causes of child mortality in China annually from 1996 to 2015 to draw implications for achievement of the SDGs for China and other low-income and middle-income countries. Methods In this systematic analysis, we adjusted empirical data on levels and causes of child mortality collected in the China Maternal and Child Health Surveillance System to generate representative estimates at the national and subnational levels. In adjusting the data, we considered the sampling design and probability, applied smoothing techniques to produce stable trends, fitted livebirth and age-specific death estimates to natvional estimates produced by the UN for international comparison, and partitioned national estimates of infrequent causes produced by independent sources to the subnational level. Findings Between 1996 and 2015, the under-5 mortality rate in China declined from 50·8 per 1000 livebirths to 10·7 per 1000 livebirths, at an average annual rate of reduction of 8·2%. However, 181 600 children still died before their fifth birthday, with 93 400 (51·5%) deaths occurring in neonates. Great inequity exists in child mortality across regions and in urban versus rural areas. The leading causes of under-5 mortality in 2015 were congenital abnormalities (35 700 deaths, 95% uncertainty range UR 28 400–45 200), preterm birth complications (30 900 deaths, 24 200–40 800), and injuries (26 600 deaths, 21 000–33 400). Pneumonia contributed to a higher proportion of deaths in the western region of China than in the eastern and central regions, and injury was a main cause of death in rural areas. Variations in cause-of-death composition by age were also examined. The contribution of preterm birth complications to mortality decreased after the neonatal period; congenital abnormalities remained an important cause of mortality throughout infancy, whereas the contribution of injuries to mortality increased after the first year of life. Interpretation China has achieved a rapid reduction in child mortality in 1996–2015. The decline has been widespread across regions, urban and rural areas, age groups, and cause-of-death categories, but great disparities remain. The western region and rural areas and especially western rural areas should receive most attention in improving child survival through enhanced policy and programmes in the Sustainable Development Goals era. Continued investment is crucial in primary and secondary prevention of deaths due to congenital abnormalities, preterm birth complications, and injuries nationally, and of deaths due to pneumonia in western rural areas. The study also has implications for improving child survival and civil registration and vital statistics in other low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.
Ultrasound is a critical non-invasive test for preoperative diagnosis of ovarian cancer. Deep learning is making advances in image-recognition tasks; therefore, we aimed to develop a deep ...convolutional neural network (DCNN) model that automates evaluation of ultrasound images and to facilitate a more accurate diagnosis of ovarian cancer than existing methods.
In this retrospective, multicentre, diagnostic study, we collected pelvic ultrasound images from ten hospitals across China between September 2003, and May 2019. We included consecutive adult patients (aged ≥18 years) with adnexal lesions in ultrasonography and healthy controls and excluded duplicated cases and patients without adnexa or pathological diagnosis. For DCNN model development, patients were assigned to the training dataset (34 488 images of 3755 patients with ovarian cancer, 541 442 images of 101 777 controls). For model validation, patients were assigned to the internal validation dataset (3031 images of 266 patients with ovarian cancer, 5385 images of 602 with benign adnexal lesions), external validation datasets 1 (486 images of 67 with ovarian cancer, 933 images of 268 with benign adnexal lesions), and 2 (1253 images of 166 with ovarian cancer, 5257 images of 723 benign adnexal lesions). Using these datasets, we assessed the diagnostic value of DCNN, compared DCNN with 35 radiologists, and explored whether DCNN could augment the diagnostic accuracy of six radiologists. Pathological diagnosis was the reference standard.
For DCNN to detect ovarian cancer, AUC was 0·911 (95% CI 0·886–0·936) in the internal dataset, 0·870 (95% CI 0·822–0·918) in external validation dataset 1, and 0·831 (95% CI 0·793–0·869) in external validation dataset 2. The DCNN model was more accurate than radiologists at detecting ovarian cancer in the internal dataset (88·8% vs 85·7%) and external validation dataset 1 (86·9% vs 81·1%). Accuracy and sensitivity of diagnosis increased more after DCNN-assisted diagnosis than assessment by radiologists alone (87·6% 85·0–90·2 vs 78·3% 72·1–84·5, p<0·0001; 82·7% 78·5–86·9 vs 70·4% 59·1–81·7, p<0·0001). The average accuracy of DCNN-assisted evaluations for six radiologists reached 0·876 and were significantly augmented when they were DCNN-assisted (p<0·05).
The performance of DCNN-enabled ultrasound exceeded the average diagnostic level of radiologists matched the level of expert ultrasound image readers, and augmented radiologists’ accuracy. However, these observations warrant further investigations in prospective studies or randomised clinical trials.
National Key Basic Research Program of China, National Sci-Tech Support Projects, and National Natural Science Foundation of China.
Summary Background MicroRNAs (miRNAs) can be used as prognostic biomarkers in many types of cancer. We aimed to identify miRNAs that were prognostic in patients with nasopharyngeal carcinoma. Methods ...We retrospectively analysed miRNA expression profiles in 312 paraffin-embedded specimens of nasopharyngeal carcinoma from Sun Yat-sen University Cancer Center (Guangzhou, China) and 18 specimens of non-cancer nasopharyngitis. Using an 873 probe microarray, we assessed associations between miRNA signatures and clinical outcome in a randomly selected 156 samples (training set) and validated findings in the remaining 156 samples (internal validation set). We confirmed the miRNAs signature using quantitative RT-PCR analysis in 156 samples from a second randomisation of the 312 samples, and validated the miRNA signature in 153 samples from the West China Hospital of Sichuan University in Chengdu, China (independent set). We used the Kaplan-Meier method and log-rank tests to estimate correlations of the miRNA signature with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival. Findings 41 miRNAs were differentially expressed between nasopharyngeal carcinoma and non-cancer nasopharyngitis tissues. A signature of five miRNAs, each significantly associated with DFS, was identified in the training set. We calculated a risk score from the signature and classified patients as high risk or low risk. Compared with patients with low-risk scores, patients with high risk scores in the training set had shorter DFS (hazard ratio HR 2·73, 95% CI 1·46–5·11; p=0·0019), DMFS (3·48, 1·57–7·75; p=0·0020), and overall survival (2·48, 1·24–4·96; p=0·010). We noted equivalent findings in the internal validation set for DFS (2·47, 1·32–4·61; p=0·0052), DMFS (2·28, 1·09–4·80; p=0·030), and overall survival (2·87, 1·38–5·96; p=0·0051) and in the independent set for DFS (3·16, 1·65–6·04; p=0·0011), DMFS (2·39, 1·05–5·42; p=0·037), and overall survival (3·07, 1·34–7·01; p=0·0082). The five-miRNA signature was an independent prognostic factor. A combination of this signature and TNM stage had better prognostic value than did TNM stage alone in the training set (area under receiver operating characteristics 0·68 95% CI 0·60–0·76 vs 0·60 0·52–0·67; p=0·013), the internal validation set (0·70 0·61–0·78 vs 0·61 0·54–0·68; p=0·012), and the independent set (0·70 0·62–0·78 vs 0·63 0·56–0·69; p=0·032). Interpretation Identification of patients with the five-miRNA signature might add prognostic value to the TNM staging system and inform treatment decisions for patients at high risk of progression. Funding Science Foundation of Chinese Ministry of Health, National Natural Science Foundation of China, Pearl River Scholar Funded Scheme, Guangdong Key Scientific and Technological Innovation Program, Guangdong Natural Science Foundation, Fundamental Research Funds for the Central Universities.
Background In patients with vitiligo, an increased reactive oxygen species (ROS) level has been proved to be a key player during disease initiation and progression in melanocytes. Nevertheless, ...little is known about the effects of ROS on other cells involved in the aberrant microenvironment, such as keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and was recently found to mediate homing of CD8+ T cells in human skin. Objective We sought to explicate the effect of oxidative stress on human keratinocytes and its capacity to drive CD8+ T-cell trafficking through CXCL16 regulation. Methods We first detected putative T-cell skin-homing chemokines and ROS in serum and lesions of patients with vitiligo. The production of candidate chemokines was detected by using quantitative real-time PCR and ELISA in keratinocytes exposed to H2 O2 . Furthermore, the involved mediators were analyzed by using quantitative real-time PCR, Western blotting, ELISA, and immunofluorescence. Next, we tested the chemotactic migration of CD8+ T cells from patients with vitiligo mediated by the CXCL16-CXCR6 pair using the transwell assay. Results CXCL16 expression increased and showed a positive correlation with oxidative stress levels in serum and lesions of patients with vitiligo. The H2 O2 -induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways: kinase RNA (PKR)–like ER kinase–eukaryotic initiation factor 2α and inositol-requiring enzyme 1α–X-box binding protein 1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6+ CD8+ T cells derived from patients with vitiligo. CXCR6+ CD8+ T-cell skin infiltration is accompanied by melanocyte loss in lesions of patients with vitiligo. Conclusion Our study demonstrated that CXCL16-CXCR6 mediates CD8+ T-cell skin trafficking under oxidative stress in patients with vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least in part, caused by unfolded protein response activation.
Summary Background Human infections with different avian influenza viruses—eg, H5N1, H9N2, and H7N9—have raised concerns about pandemic potential worldwide. We report the first human infection with a ...novel reassortant avian influenza A H10N8 virus. Methods We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. Findings A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226–228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein—which is associated with mammalian adaptation—was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. Interpretation The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient. Funding Emergency Research Project on human infection with avian influenza H7N9 virus, the National Basic Research Program of China, and the National Mega-projects for Infectious Diseases.
PDF
