Antibiotic Expenditure by Public Healthcare Institutions in Shandong Province in China, 2012–2016

Background: Overuse of antibiotics may not only increase the burden of antimicrobial resistance, but also accelerate the growth of healthcare expenditures. China has issued a series of policies to improve antibiotic use and reduce the cost of medicine in healthcare institutions. This study aimed to evaluate the trends of antibiotic expenditure in public healthcare institutions in Shandong from 2012 to 2016 and to assess antibiotic expenditure by drug class and the level of healthcare institutions.Methods: We collected data from the centralized bidding procurement (CBP) system in Shandong province between 2012 and 2016. Governmental health facilities including secondary and tertiary hospitals, and urban and rural primary healthcare centers (PHCs) procured antibiotics via this system. Antibiotics were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. Antibiotic expenditure was assessed using total annual expenditure (US dollars) and expenditure per person per year (US dollars).Results: The overall antibiotic expenditure was $717 million in 2016, a 56% increase compared to 2012. Parenteral antibiotics accounted for 84% of the total antibiotic expenditure in 2016. Most of the antibiotics were procured by secondary and tertiary hospitals (33 and 44%, respectively). The expenditures continuously increased in secondary hospitals, tertiary hospitals, and urban PHCs from 2012 to 2016, while antibiotic procurement decreased in urban PHCs since 2015. The third-generation cephalosporins (J01DD) were among the top five ATC classes of antibiotics in all healthcare institutions. Fluoroquinolones (J01MA) were commonly procured by tertiary hospitals, rural and urban PHCs. The expenditure on carbapenems (J01DH) raised sharply in tertiary hospitals.Conclusions: The overall antibiotic expenditure kept increasing in the public healthcare institutions in Shandong. The trends of increasing expenditure began to decline in 2016, which may be associated with antibiotic stewardship initiatives. The expenditure for expensive and critical important classes of antibiotics increased, therefore it is of importance to develop policies on improving the rational use of antibiotics

Response of "Glacier-Runoff" system in a typical monsoonal temperate glacier region, Hailuogou Basin in Mt. Gongga of China, to global warming

International audienceThe method of correlation analysis and trend analysis were used in this research in order to confirm the response of "glacier-runoff" system to global warming. Hailuogou glacier had retreated by 1871.8 m over the past 76 years, Hailuogou No. 2 glacier had also retreated by 1100 m. Glaciers retreats are contrary to the climatic warming trend in China and the Northern Hemisphere. Glaciers in Hailuogou basin were in the loss with a fluctuating manner since 1950s, and accumulative value of mass balance is ?10 825.5 mm water equivalent with an annual mean value of ?240.6 mm. The inverse correlation is highly significant between mass balance variation and climatic fluctuation of China and the Northern Hemisphere after 1950s. Glacier ablation is intensive with a ratio of 7.86 m yr?1. A steady rise tendency toward glaciers runoff has been observed since 1980s, and the runoff rise is mainly responsible for melt water in Hailuogou basin. It is noticeable that climatic warming not only strengthened ablation extent and enlarged ablation area, but also prolonged ablation period. Global warming is the main cause of glacier retreat, mass loss and runoff rise in Hailuogou basin

Spatial−temporal variation of ecological environment quality and driving factors from 2000 to 2020 in Wuliangsu Lake Basin, Northern China

Due to global climate change and the intensification of human activities, the ecological function of Wuliangsu Lake Basin has been seriously degraded. Obtaining accurate spatial–temporal dynamics of regional ecological environment quality is essential for the evaluation of ecological management and restoration effects. This study assessed the trend changes and drivers of the Remote Sensing Ecological Index (RSEI) in the Wuliangsu Lake Basin from 2000−2020. Firstly, the trend analysis method and hurst index were used to analyze the temporal and spatial variation of RSEI. Then the main factors of RSEI variation were analyzed using meteorological data, integrated nighttime lighting data, and population density data. Overall, the RSEI shows an increasing trend from the west to the east with a rate of 0.0034 year−1 over the last 21 years. The area change of RSEI was 54.22%, 63.80% and 52.43% for 2000−2006, 2007−2013 and 2014−2020, respectively, which indicates that most areas have a stable ecological environment. However, the overall Future Improvement Trend (FIT) area of RSEI is 42.21%, mainly in Dengkou area, Urad Qianqi and central area. This indicates that the RSEI remains stable locally and shows an overall improving trend. The results of the correlation analysis showed that the areas influenced by meteorological and human factors were highly coincident, mainly in Dengkou and northern Linhe areas and Urad Qianqi. Considering the lagging effect of ecological engineering, the sustainable development status of RSEI in the western and eastern regions will maintain an improving trend in the future. Our study confirms the complex relationship between RSEI and meteorological and human activities, which is crucial for the scientific management of watershed ecosystems under the influence of anthropogenic factors

The Effect of Chinese Herbal Medicine on Quality of Life and Exercise Tolerance in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Chinese herbal medicine (CHM) has a good effect of alleviating symptoms and improving quality of life and exercise tolerance in patients with heart failure with preserved ejection fraction (HFpEF), but it wasn't sufficiently valued and promoted because of the lack of evidence-based medical evidence.Aim: To systematically review the effect of CHM on quality of life and exercise tolerance in patients with HFpEF.Methods: We conducted a systematic literature search for Chinese and English studies in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China Knowledge Resource Integrated Database, Wanfang Data, and China Science and Technology Journal Database. Databases were searched using terms relating to or describing CHM, HFpEF and randomized controlled trials, without any exclusion criteria for other types of diseases or disorders. Literature retrieval, data extraction, and risk of bias assessments were performed independently by two investigators. Differences were resolved by consensus. RevMan 5.3.0 was used for data analysis. Quantitative synthesis was used when the included studies were sufficiently homogeneous and subgroup analyses were performed for studies with different sample sizes and blind methods. GRADEpro was used to grade the available evidence to minimize bias in our findings.Results: Seventeen studies with 2,724 patients were enrolled in this review. ROB assessments showed a relatively high selection and performance bias. Meta-analyses showed that compared with conventional western medicine, combined CHM and conventional western medicine could significantly improve 6-min walk distance (MD = 52.13, 95% CI [46.91, 57.34], P < 0.00001), and it seemed to be more effective as compared with combined placebo and conventional western medicine. Similar results were observed for quality of life and the results were better in a larger sample. The GRADEpro showed a very low to moderate level of the available evidence.Conclusion: Combined CHM and conventional western medicine might be effective to improve exercise tolerance and quality of life in HFpEF patients, but new well-designed studies with larger sample size, strict randomization, and clear description about detection and reporting processes are needed to further strengthen this evidence

Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement

IntroductionTreatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) shows poor response rates in non–germinal center B cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients with multiple extranodal involvement. This study aims to evaluate anti-tumor activity and safety of zanubrutinib with R-CHOP (ZR-CHOP) in treatment naïve non-GCB DLBCL with extranodal involvement.MethodsIn this single-arm, phase 2, prospective, single-center study, patients with newly diagnosed non-GCB DLBCL with extranodal involvement enrolled between October 2020 to March 2022 received ZR-CHOP for 6 cycles followed by 2 cycles of maintenance treatment with rituximab and zanubrutinib. The primary endpoint included progression-free survival (PFS) in the intent-to-treat (ITT) population whereas the secondary endpoints included overall response rate (ORR), complete response (CR), and duration of response. Further, next-generation sequencing (NGS) was used for detection of different oncogenic mutations closely related to DLBCL pathogenesis.ResultsFrom October 2020 to March 2022, 26 patients were enrolled, and 23 of them were evaluated for efficacy after receiving 3 cycles of ZR-CHOP treatment. 1-year PFS and OS were 80.8% and 88.5% respectively while expected PFS and OS for 2-years are 74.0% and 88.5% respectively with median follow-up of 16.7 months and ORR was 91.3% (CR: 82.61%; PR: 8.70%). Oncogenic mutations closely related to DLBCL pathogenesis were assessed in 20 patients using NGS. B-cell receptor and NF-κB pathway gene mutations were detected in 10 patients, which occurred in MYD88 (7/19), CD79B (4/19), CARD11 (5/19), and TNFAIP3 (2/19). Hematological adverse events (AEs) ≥ grade 3 included neutropenia (50%), thrombocytopenia (23.1%), and anemia (7.7%) whereas non-hematological AEs ≥ grade 3 included pulmonary infection (19.2%).ConclusionZR-CHOP is safe and effective for treating treatment naïve non-GCB DLBCL patients with extranodal involvement.Clinical Trial RegistrationClinicaltrials.gov, NCT0483587

Conventional and genetic evidence on alcohol and vascular disease aetiology:a prospective study of 500 000 men and women in China

Background Moderate alcohol intake has been associated with reduced cardiovascular risk in many studies, in comparison with abstinence or with heavier drinking. Studies in east Asia can help determine whether these associations are causal, since two common genetic variants greatly affect alcohol drinking patterns. We used these two variants to assess the relationships between cardiovascular risk and genotype-predicted mean alcohol intake in men, contrasting the findings in men with those in women (few of whom drink). Methods The prospective China Kadoorie Biobank enrolled 512 715 adults between June 25, 2004, and July 15, 2008, from ten areas of China, recording alcohol use and other characteristics. It followed them for about 10 years (until Jan 1, 2017), monitoring cardiovascular disease (including ischaemic stroke, intracerebral haemorrhage, and myocardial infarction) by linkage with morbidity and mortality registries and electronic hospital records. 161 498 participants were genotyped for two variants that alter alcohol metabolism, ALDH2-rs671 and ADH1B-rs1229984. Adjusted Cox regression was used to obtain the relative risks associating disease incidence with self-reported drinking patterns (conventional epidemiology) or with genotype-predicted mean male alcohol intake (genetic epidemiology—ie, Mendelian randomisation), with stratification by study area to control for variation between areas in disease rates and in genotype-predicted intake. Findings 33% (69 897/210 205) of men reported drinking alcohol in most weeks, mainly as spirits, compared with only 2% (6245/302 510) of women. Among men, conventional epidemiology showed that self-reported alcohol intake had U-shaped associations with the incidence of ischaemic stroke (n=14 930), intracerebral haemorrhage (n=3496), and acute myocardial infarction (n=2958); men who reported drinking about 100 g of alcohol per week (one to two drinks per day) had lower risks of all three diseases than non-drinkers or heavier drinkers. In contrast, although genotype-predicted mean male alcohol intake varied widely (from 4 to 256 g per week—ie, near zero to about four drinks per day), it did not have any U-shaped associations with risk. For stroke, genotype-predicted mean alcohol intake had a continuously positive log-linear association with risk, which was stronger for intracerebral haemorrhage (relative risk [RR] per 280 g per week 1·58, 95% CI 1·36–1·84, p Interpretation Genetic epidemiology shows that the apparently protective effects of moderate alcohol intake against stroke are largely non-causal. Alcohol consumption uniformly increases blood pressure and stroke risk, and appears in this one study to have little net effect on the risk of myocardial infarction.</p

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Hopf bifurcation of an HIV-1 virus model with two delays and logistic growth

The paper establish and investigate an HIV-1 virus model with logistic growth, which also has intracellular delay and humoral immunity delay. The local stability of feasible equilibria are established by analyzing the characteristic equations. The globally stability of infection-free equilibrium and immunity-inactivated equilibrium are studied using the Lyapunov functional and LaSalles invariance principle. Besides, we prove that Hopf bifurcation will occur when the humoral immune delay pass through the critical value. And the stability of the positive equilibrium and Hopf bifurcations are investigated by using the normal form theory and the center manifold theorem. Finally, we confirm the theoretical results by numerical simulations

Social Network-Based Content Delivery in Device-to-Device Underlay Cellular Networks Using Matching Theory

With the popularity of social network-based services, the unprecedented growth of mobile date traffic has brought a heavy burden on the traditional cellular networks. Device-to-device (D2D) communication, as a promising solution to overcome wireless spectrum crisis, can enable fast content delivery based on user activities in social networks. In this paper, we address the content delivery problem related to optimization of peer discovery and resource allocation by combining both the social and physical layer information in D2D underlay networks. The social relationship, which is modeled as the probability of selecting similar contents and estimated by using the Bayesian nonparametric models, is used as a weight to characterize the impact of social features on D2D pair formation and content sharing. Next, we propose a three-dimensional iterative matching algorithm to maximize the sum rate of D2D pairs weighted by the intensity of social relationships while guaranteeing the quality of service (QoS) requirements of both cellular and D2D links simultaneously. Moreover, we prove that the proposed algorithm converges to a stable matching and is weak Pareto optimal, and also provide the theoretical complexity. Simulation results show that the algorithm is able to achieve more than 90% of the optimum performance with a computation complexity one thousand times lower than the exhaustive matching algorithm. It is also demonstrated that the satisfaction performance of D2D receivers can be increased significantly by incorporating social relationships into the resource allocation design.peerReviewe