Search

The Chinese healthcare system faces a dilemma between its hospital-centric approach to healthcare delivery and a rapidly ageing population that requires strong primary care. To improve system efficiency and continuity of care, the Hierarchical Medical System (HMS) policy package was issued in November 2014 and fully implemented in 2015 in Ningbo, Zhejiang province, China. This study aimed to investigate the impact of the HMS on the local healthcare system. We conducted a repeated cross-sectional study with quarterly data collected between 2010 and 2018 from Yinzhou district, Ningbo. The data were analysed with an interrupted time series design to assess the impact of HMS on the changes in levels and trends of three outcome variables: primary care physicians’ (PCPs’) patient encounter ratio (i.e. the mean quarterly number of patient encounters of PCPs divided by that of all other physicians), PCP degree ratio (i.e. the mean degree of PCPs divided by the mean degree of all other physicians, with the mean degree revealing the mean activity and popularity of physicians, which reflected the extent to which he/she coordinated with others in delivering health services), and PCP betweenness centrality ratio (i.e. the mean betweenness centrality of PCPs divided by the mean betweenness centrality of all other physicians; the mean betweenness centrality was interpreted as the mean relative importance of physicians within the network, indicating the centrality of the network). Observed results were compared with counterfactual scenarios computed based on pre-HMS trends. Between January 2010 and December 2018, 272 267 patients visited doctors for hypertension, a representative non-communicable disease with a high prevalence of 44.7% among adults aged 35–75 years, amounting to a total of 9 270 974 patient encounters. We analysed quarterly data of 45 464 observations over 36 time points. Compared to the counterfactual, by the fourth quarter of 2018, the PCP patient encounter ratio rose by 42.7% [95% confidence interval (CI): 27.1–58.2, P

Defect-engineered SnS2−x has been demonstrated for the first time as an efficient p-block catalyst for electrocatalytic NO reduction to NH3 (NORR), attributed to the active Sn-VS sites that selectively activate NO and reduce the energy barriers of the NORR pathway.

A rare-earth La-doped VS2−x is reported as an effective catalyst for electrocatalytic nitrate-to-ammonia conversion, which is attributed to the synergy of La-dopants and S-vacancies to promote NO3RR and suppress hydrogen evolution.

Post-vaccination safety is a major public health concern. The genetic predisposition on immune response has not been clearly identified. Clarifying whether individual genetic predisposition plays a role on adverse events (AEs) is critical for the prevention of AEs. From July 2019 to June 2020, we performed a case-control study among children aged 3–24 months in seven Chinese provinces. Each child received a combination vaccination against diphtheria, tetanus, acellular pertussis, and Haemophilus influenzae type b (DTaP-Hib). Through daily telephone follow-up, we collected AEs within seven days. Oral swab samples were collected to investigate the effects of single nucleotide polymorphisms (SNPs) on the risk of AEs. 304 participants were included in the study. In univariate analysis, we discovered three protective SNPs (rs452204, OR = 0.67, P = 0.0352; rs9282763 and rs839, OR = 0.64, P = 0.0256) and one risk SNP (rs9610, OR = 2.20, P = 0.0397). In multivariate analysis, the effects of rs452204 and rs839 were found to be stable. The interaction between rs452204 and rs9610 was observed (OR = 7.25, 95% CI: 1.44–36.58, P = 0.0165). Genetic predisposition was associated with the risk of AEs after DTaP-Hib vaccination, emphasizing the potential application in the prevention of AEs.

Imported Coronavirus disease 2019 (COVID-19) patients pose a huge challenge to the prevention and control of the epidemic in prefecture-level cities in China. However, the treatment strategies at that time were mainly empirical and far from perfect. Hence, this study aims to summarize the clinical characteristics, diagnosis and treatment of all COVID-19 patients in Jiaxing City in 2020.The clinical data of 42 patients diagnosed with COVID-19 in Jiaxing City, Zhejiang Province from January 23, 2020 to March 4, 2020 were retrospectively analyzed. Epidemiological history and sociodemographic data were collected. Laboratory parameters, imaging and disease progression, treatment methods, efficacy and adverse reactions of COVID-19 cases were recorded. Then, the clinical characteristics as well as diagnosis and treatment were statistically analyzed.The median age of 42 patients was 47 years old, including 24 males (57.1%) and 18 females (42.9%). There were 21 first-generation cases, 29 cases (69%) of clustering onset related to first-generation cases, and 28 cases without any underlying diseases. Radiographic progression was reported in 17 patients (40.5%) (progression duration, 2-11 days; median progression duration, 3.8 days; average progression duration, 4.59-2.48 days). The main clinical symptoms include fever (78.6%) and cough (64.3%). A total of 37 patients (88.10%) received arbidol combined with lopinavir/ritonavir or darunavir/cobicistat. Of these, 22 patients (52.4%) took a combination with moxifloxacin tablets, and 20 patients (47.6%) took combined hormone therapy. Seventeen patients (40.48%) reported diarrhea, nausea, vomiting, rash, and other adverse drug reactions. A total of 38 patients improved (90.5%). The hospital stays of 36 patients ranged from 7 to 33 days, with a median of 19 days (19.00-7.33 days on average). The virus nucleic acid test result return time was 1 to 32 days, with a median of 15.5 days (14.41-8.61 days on average).Most of the imported COVID-19 patients in Jiaxing City were of the first generation, mainly cluster onset, and the epidemiological characteristics were relatively simple. Arbidol combined with lopinavir/ritonavir or darunavir/cobicistat was the main treatment strategy for the initial treatment of COVID-19.

For the purpose of environmental protection, the solution to the excessive release of carbon dioxide in the atmosphere has become the focus of current research. The electrochemical reduction of carbon dioxide, which enables the capture and storage of carbon dioxide and its conversion into new compounds, has shown its effectiveness. By studying various methods of preparing CO2 absorption electrodes, Carbon fiber material is considered as a promising electrode material due to its good electrical conductivity and availability. In this paper, Ag/PTFE composites (Silver as catalyst, PTFE as hydrophobic agent), combined with carbon fibers, are used as Gas diffusion electrodes (GDE) materials. After verifying its hydrophobicity by contact angle measurement, the performance of electrode is tested. The results show that the new electrodes synthesised are suitable for use as Gas diffusion electrodes materials (GDE) and that Ag catalysts combined with carbon nanofibers can be used for the electrochemical reduction of CO2.

Ni/Al energetic structural materials were prepared by vacuum hot-pressing method and then treated by secondary treatment of cold rolling or cold isostatic pressing. The effects of secondary treatment on the surface morphology, the phase composition, density, exothermic properties and tensile properties of Ni/Al energetic structural materials were investigated. The results showed that the density, the reaction energy density and the sensitivity of energetic materials improved significantly by the secondary treatment of cold rolling or cold isostatic pressing. It was also found that, after cold rolling and cold isostatic pressing, the energy density increased from 780 J/g to 1089 J/g and 993 J/g, respectively, and the initial reaction temperature was advanced by 46 °C and 14°C simultaneously. This is related to the increased in the contact area between Al particles and Ni particles. Meanwhile, the tensile strength increased from 166.7 MPa to 254.8 MPa and 211.3 MPa, respectively.

Although anti-programmed death receptor-1 (PD-1) agents have been evaluated in the neoadjuvant setting for the treatment of locally advanced head and neck cancer, including oral cavity squamous cell carcinoma (OCSCC), the overall response rate is modest. The aim of the present study was to evaluate the efficacy and safety of neoadjuvant nivolumab in combination with stereotactic body radiotherapy (SBRT) for the treatment of locally advanced OCSCC.OCSCC patients who underwent surgical resection within 6 months of treatment with nivolumab plus SBRT from December 2018 to February 2021 were analyzed retrospectively.All 30 eligible patients enrolled in this study well tolerated the neoadjuvant treatment with no serious adverse events (AEs). Of them, 27 patients (90.0%) achieved R0 resection, and 5 patients (16.7%) experienced procedure-associated complications. The complete response (CR), partial response (PR) and stable disease (SD) were 10.0%, 46.7% and 43.3% respectively. The major pathological response (MPR), complete pathological response (pCR) and clinical to pathological downstaging rate were 60.0%, 33.3% and 83.3% respectively. During the median follow-up period of 13.5 months, 26 patients (86.7%) who underwent surgical resection remained alive. The disease-free survival (DFS) and overall survival (OS) at 24 months were 70.4% and 76.4% respectively.Neoadjuvant nivolumab plus SBRT is safe and efficacious, and could be used as a potential neoadjuvant option for the treatment of patients with locally advanced OCSCC.

Purpose: Statin therapy has been shown to prevent major vascular events in a wide range of individuals, but the risk of intracerebral hemorrhage (ICH) from statin use is unclear. We aimed to determine the ICH risk since statin initiation for older patients. Methods: Based on 2011-2020 year data from the Yinzhou Regional Health Care Database, patients aged 50 years or older who have no history of ICH and statin use were included in the framework of target trial emulation, and then were categorized as statin initiators and non-initiators according to their initial statin assignment during 3-month recruitment periods. The statin initiators and non-initiators in each emulated trials were matched by using propensity score and then were stacked together. Cox proportional hazards model was used to estimate the association between ICH risk and statin treatment. Results: With a median follow-up of 7.75 (interquartile range 6.75-8.75) years, 37,659 statins initiators and their 1:1 matched non-initiators were analysed where the hazard ratio of ICH between statin initiators and non-initiators were 1.09 (95% confidence interval: 0.92–1.29). The results are consistent across several subgroups and sensitivity analyses. Conclusions: no association was found between ICH risk and statin use among older patients without prior ICH, suggesting no need to avoid potential statin prescribing due to concerns of evaluated ICH risk.

Supplementary Table 1 shows the list of 4C primers applied in the Circular Chromosome Conformation Capture assay.

Supplementary Materials and Methods shows detailed descriptions of methodology or materials and methods used in this manuscript.

Supplementary Figures, including Figures S1-6, and each figure legends.

Supplementary Table 4 shows the sequences of SE fragments inserted into pGL3 vector

Supplementary Table 5 shows the results of NSD2-MASPEC in KMS11 cells.

Supplementary Table 2 shows 26 SE-associated genes commonly acquired in both t(4:14)-positive HMCLs and patient-derived MM sample.

Multiple myeloma is an incurable malignancy with marked clinical and genetic heterogeneity. The cytogenetic abnormality t(4;14) (p16.3;q32.3) confers aggressive behavior in multiple myeloma. Recently, essential oncogenic drivers in a wide range of cancers have been shown to be controlled by super-enhancers (SE). We used chromatin immunoprecipitation sequencing of the active enhancer marker histone H3 lysine 27 acetylation (H3K27ac) to profile unique SEs in t(4;14)-translocated multiple myeloma. The histone chaperone HJURP was aberrantly overexpressed in t(4;14)-positive multiple myeloma due to transcriptional activation by a distal SE induced by the histone lysine methyltransferase NSD2. Silencing of HJURP with short hairpin RNA or CRISPR interference of SE function impaired cell viability and led to apoptosis. Conversely, HJURP overexpression promoted cell proliferation and abrogated apoptosis. Mechanistically, the NSD2/BRD4 complex positively coregulated HJURP transcription by binding the promoter and active elements of its SE. In summary, this study introduces SE profiling as an efficient approach to identify new targets and understand molecular pathogenesis in specific subtypes of cancer. Moreover, HJURP could be a valuable therapeutic target in patients with t(4;14)-positive myeloma.Significance:A super-enhancer screen in t(4;14) multiple myeloma serves to identify genes that promote growth and survival of myeloma cells, which may be evaluated in future studies as therapeutic targets.

Supplementary Table 3 Uni- and multivariate Cox survival analysis using HJURP and NSD2 expression in myeloma dataset

Background. Erythronium japonicum Decne (Liliaceae) is an early spring ephemeral with an underground initial floral differentiation stage. The flowering mechanism is crucial in ornamental plants due to the associated economic value. Therefore, this study is aimed at exploring the metabolic landscape during floral differentiation, including flower primordium, perianth, stamen, and the pistil differentiation period, in E. japonicum coupled with a conjoint analysis of the metabolome and transcriptome. Using ultraperformance liquid chromatography-tandem mass spectrometry, we identified 586 metabolites from 13 major metabolite classes. Comparative metabolomics between different floral developmental stages revealed several abundant metabolites during the respective phases. Upaccumulation of p-coumaroylputrescine, scopoletin, isorhoifolin, cosmosiin, genistin, and LysoPC 15 : 0 emphasized the significance of these compounds during flower development. Furthermore, previously identified DEGs, viz., EARLY FLOWERING 3, Flowering locus K, PHD finger-containing protein, and zinc finger SWIM domain-containing protein for floral differentiation, depicted a high correlation with lipid, flavonoid, and phenolics accumulation during floral developmental stages. Conclusions. Together, the results improve our interpretation of the underground floral development in E. japonicum.

Osteosarcoma (OS) is one of the most common malignant tumors in adolescents. Due to local invasion, distant metastasis and drug resistance, the clinical treatment efficacy and prognosis of OS have remained almost unchanged for decades. Epigallocatechin-3-gallate (EGCG) is a unique catechin from tea leaves, and some studies have confirmed its antitumour effects on various tumors. Here, cellular experiments showed that EGCG significantly promoted OS cell apoptosis and inhibited proliferation, migration and invasion, and cell and animal experiments demonstrated that the Wnt/β-catenin pathway played an indispensable role in the antitumour effects of EGCG. Moreover, EGCG inhibited the growth of OS cells in vitro while suppressing tumor cell damage to the bone in situ and distant lung metastasis. The results indicate that the antitumour effect of EGCG on human OS may be mediated by regulating the Wnt/β-catenin pathway and that EGCG can be used alone or in combination with other regimens as a potentially effective anticancer treatment.

Background: OVERSTEP is a multicenter, randomized clinical trial of capecitabine (CAP) versus endocrine therapy (HT) as maintenance therapy after 1st-line CAP-based combination chemotherapy in HR+/HER2- ABC/MBC. At 2020 SABCS conference, we have reported the primary endpoint (progression-free survival, PFS) of the OVERSTEP (NCT02597868) trial. With a median follow-up of 24.3 months,Median PFS (mPFS) of HT cohort was significantly longer than that of CAP group (17.5 months vs. 12.2 months, HR=0.625, 95%CI: 0.429-0.909, P=0.013). In this annual meeting, we will report the update of mPFS and the secondary endpoint (overall survival, OS). Methods: HR+ and HER2- metastatic breast cancer were enrolled in this study. All patients were histologically confirmed and received at least 4 cycles of CAP-based combination regimen as 1st-line salvage chemotherapy. The patients who achieved CR, PR or durable SD by RECIST criteria entered into the maintenance therapy setting (MT), and randomly (1:1 ratio) assigned to either CAP single or HT group. Randomization was done centrally with stratification by endocrine sensitive or resistance and visceral or non-visceral metastasis. The primary endpoint was mPFS, and the secondary endpoint was overall survival (OS), safety, et al. The superiority test was performed in all patients who received at least one dose maintenance therapy. The last follow-up ended in June 30, 2021. The medium follow-up duration was 41.4 months and the OS event was mature. Results: A total of 181 eligible patients were enrolled in this study from Jun 5, 2013 to Jan 14, 2019. After combined chemotherapy, 75.14% (n=136) cases entered into the maintenance therapy setting, and 24.86% case were disease progressed (PD) during combined chemotherapy. After a median follow-up of 41.4 months (IQR 21.57-79.23), the update mPFS in HT group remained superior to CAP cohort (17.7 months vs. 12.2 months, P=0.011). In addition, the median maintenance duration of HT group was significantly longer than that of CAP group (13.8 months vs. 7.4 months, P= 0.008). For endocrine sensitive patients, mPFS was greatly prolonged in HT group compared to CAP cohort (29.3 months vs. 14.8 months, HR=0.515, 95%CI: 0.269-0.988, P=0.042). Besides, in non-visceral metastasis patients, median PFS of HT group was 25.3 months which was longer than CAP subgroup 17.0 months (HR=0.54, 95%CI: 0.300-0.972, P=0.037). However, in endocrine resistance patients, there was no significant difference between HT and CAP group (13.6 months vs. 12.0 months, HR=0.791, 95%CI: 0.499-1.253, P=0.314). There was no difference observed between HT and CAP group in visceral involved cases (14.3 months vs. 11.0 months, HR= 0.668, 95%CI: 0.410-1.089, P=0.101). The median OS was 51.7 months (95%CI: 36.614-66.786) in HT cohort and 39.8 months (95%CI:14.083-65.517) in CAP group, respectively (HR=0.882, 95%CI: 0.550-1.414, P=0.600). Conclusions: For HR+ and HER2- MBC, after 1st-line salvage combined chemotherapy, HT maintenance therapy demonstrated sustained better survival benefits than CAP, especially for hormone sensitive or non-visceral involved patients. The primary endpoint of this study was successfully reached and the median OS was prolonged by 11.9-months. Citation Format: Xiao-Jia Wang, Jian Huang, Xi-ying Shao, Li Cai, Yong-mei Yin, Li-li Zhang, Peng Shen, Yan-xia Shi. Hormone therapy (HT) brings more survival benefits than capecitabine (CAP) as maintenance therapy following the 1st-line chemotherapy in HR+/HER2-ABC/MBC: Update primary endpoint of OVERSTEP(ZJCHBC001) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-04.

Aiming at the problems of insufficient image contrast in three-dimensional reconstruction of UAV in low illumination environment and the unstable iteration times of the RANSAC algorithm in the feature matching process, real-time matching method of UAV aerial image is proposed. First, a new image enhancement algorithm is applied to the image to enhance its quality and visibility. Second, the enhanced fast algorithm in ORB extracts the feature points from the preprocessed image, and cross-matching performs rough matching. Finally, the PROSAC algorithm solves the homography matrix by selecting the highest quality interior points from the extracted feature points. To improve the matching accuracy, some exterior points that do not conform to the geometric characteristics of the image are removed based on the homography matrix and the set mismatch threshold. The results show that the improved ORB algorithm is applied to the low illumination environment of UAV aerial photography, the image matching accuracy in 3D reconstruction is improved, and the correct matching rate tends to 97.24~99.39%. The relevant research findings and conclusions provide a fast and effective method for UAV image matching in different low illumination environments.

Exploring high-efficiency metal-free electrocatalysts towards N2 reduction reaction (NRR) is of great interest for the development of electrocatalytic N2 fixation technology. Herein, we combined boron nitride quantum dots (BNQDs) and graphitic carbon nitride (C3N4) to design a metal-free BNQDs/C3N4 heterostructure as an effective and durable NRR catalyst. The electronically coupled BNQDs/C3N4 presented an NH3 yield as high as 72.3 μg h−1 mg−1 (-0.3 V) and a Faradaic efficiency of 19.5% (-0.2 V), far superior to isolated BNQDs and C3N4, and outperforming nearly all previously reported metal-free catalysts. Theoretical computations unveiled that the N2 activation could be drastically enhanced at the BNQDs-C3N4 interface where interfacial BNQDs and C3N4 cooperatively adsorb N2 and stabilize *N2H intermediate, leading to the significantly promoted NRR process with an ultra-low overpotential of 0.23 V.