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To date, the optimal treatment for portal vein thrombosis (PVT) in cirrhotic patients has not been established in guidelines or consensus. We conducted a systematic review and meta-analysis to evaluate the effect of anticoagulation therapy in patients with cirrhosis and PVT. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched (until 31st October 2020) for studies evaluating the effect of anticoagulation therapy on treating PVT in patients with cirrhosis. Odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using the Mantel–Haenszel method. A total of 13 studies were included in the analysis, comprising 6005 patients. Of these, three were prospective cohort studies, nine were retrospective cohort studies and one was case–control study. Compared to no treatment, anticoagulation therapy was associated with higher rates of PVT recanalization (OR 4.29; 95% CI 3.01–6.13). Anticoagulation therapy demonstrated a significant 74% reduction in PVT extension compared to no treatment (OR 0.26; 95% CI 0.14–0.49). Anticoagulation therapy was associated with a nonsignificantly lower risk of death (OR 0.53; 95% CI 0.20–1.40). However, anticoagulation therapy was associated with slightly higher risk of bleeding compared to no treatment (OR 1.16; 95% CI 1.02–1.32). In cirrhotic patients with PVT, anticoagulation therapy helps increase rate of PVT recanalization and improve survival, but may also carry higher risks of bleeding compared to no treatment. Our findings support the use of anticoagulation in cirrhotic patients with PVT.

Purpose To evaluate the cost-utility of empagliflozin, in addition to best available standard care (BASC), for the treatment of adult patients with T2DM at high cardiovascular risk from the Chinese healthcare system perspective. Methods A Microsoft Excel-based patient-level simulation model, based on the EMPA-REG OUTCOME trial data, was adapted and used to project individual's clinical and economic outcomes over a lifetime horizon. The cost and utility values were derived from databases and published studies. Numbers and rates of diabetes-related events, life-years (LYs), quality-adjusted life-years (QALYs), costs (¥ 2019) as well as incremental cost-utility ratios (ICURs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results. Results Compared with BASC, empagliflozin plus BASC was predicted to result in an additional 1.01 QALYs (8.05 QALYs vs 7.04 QALYs) at an incremental cost of ¥4002 per patient. The modeled ICUR was ¥3988 per QALY gained, which was considered highly cost-effective in China compared to both one and three times the GDP per capita in 2019 (¥70,892 and ¥212,676). The deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results. Conclusion This is the first cost-utility analysis regarding the use of empagliflozin in patients with T2DM in China, the world's most affected country by the T2DM pandemic. The economic evaluation suggests that empagliflozin added to BASC was estimated to be a highly value-for-money option for the treatment of adult patients with T2DM at high cardiovascular risk in the Chinese healthcare setting.

Introduction The aim of this study was to compare the efficacy, safety and cost-utility (from the Chinese health insurance perspective) of lixisenatide and insulin regimens in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs). Methods A comprehensive literature search of English (PubMed and Cochrane Library) and Chinese (CNKI and WanFang) language databases was performed, and head-to-head relevant randomized controlled trials (RCTs) were retrieved and analyzed by performing a mixed-treatment comparison (MTC) meta-analysis for efficacy and safety endpoints. A cost–utility analysis was then conducted using the IQVIA CORE Diabetes Model to compare the lifetime pharmacoeconomic profiles among the treatment groups. Results Eleven RCTs were included in this MTC meta-analysis. Regarding glycated hemoglobin targets, lixisenatide was similar to both basal insulin (mean difference [MD] 0.27%; 95% credible interval [CrI] 0.02%, 0.57%) and premixed insulin (MD 0.32%; 95% CrI − 0.01%, 0.66%), respectively. Statistically significant differences were found for changes in body weight in favor of lixisenatide compared with basal insulin (MD − 3.22 kg; 95% CrI − 5.51 kg, − 0.94 kg) and premixed insulin (MD − 2.68 kg; 95% CrI − 5.16 kg, − 0.20 kg). The relative risk (RR) of symptomatic hypoglycemia associated with lixisenatide was also significantly lower than that associated with basal insulin (RR 0.22; 95% CrI 0.09, 0.52) and premixed insulin (RR 0.17; 95% CrI 0.07, 0.41). The cost–utility analysis yielded results of ¥61,072 ($8565, vs. basal insulin) and ¥127,169 ($17,836, vs. premixed insulin) per quality-adjusted life year gained, with both values falling within the willingness-to-pay threshold in China. Conclusions For T2DM patients inadequately controlled on OADs, lixisenatide was shown to be comparable to basal insulin and premixed insulin in terms of HbA1c and better than both of the latter in terms of both body weight loss and hypoglycemia. Lixisenatide was also a cost-effective treatment option from the perspective of Chinese health insurance. Electronic Supplementary Material The online version of this article (10.1007/s13300-020-00857-3) contains supplementary material, which is available to authorized users.

BackgroundIn several cardiovascular outcome trials (CVOTs), empagliflozin (SGLT-2 inhibitor), sitagliptin (DPP-4 inhibitor) and liraglutide (GLP-1 receptor agonist) + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD). This study assessed the cost-effectiveness (CE) of empagliflozin + SoC in comparison to sitagliptin + SoC and liraglutide + SoC based on the respective CVOT.MethodsThe IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the CVOT outcomes. EMPA-REG OUTCOME baseline characteristics and CVOT specific treatment effects on risk factors for cardiovascular disease (HbA1c, BMI, blood pressure, lipids) were applied. Three-year observed cardiovascular events of empagliflozin + SoC versus sitagliptin + SoC and liraglutide + SoC were derived from EMPA-REG OUTCOME and an indirect treatment comparison. Relative risk adjustments to calibrate the CDM were obtained after a trial and error process to match as closely the observed and CDM-predicted outcomes. The drug-specific treatment effects were considered up until HbA1c reached 8.5% and treatment switch occurred. After this switch, the United Kingdom Prospective Diabetes Study 82 risk equations predicted events based on co-existing risk factors and treatment intensification to basal bolus insulin were applied. The analysis was conducted from the perspective of the Chinese healthcare system applying 3% discounting. The time horizon was lifelong.ResultsEmpagliflozin + SoC provides additional Quality Adjusted Life years (QALY + 0.564) for an incremental cost of 42,497RMB (US$6053) compared to sitagliptin + SoC, resulting in an Incremental Cost Utility Ratio of 75,349RMB (US$10,732), thus below the willingness-to-pay threshold of 212,676RMB, corresponding to three times the Gross Domestic Product in China (2019). Compared to liraglutide + SoC, empagliflozin + SoC use leads to 0.211QALY gained and cost savings of 71,427RMB (US$10,173) and is as such dominant. Scenario and probabilistic sensitivity analyses demonstrated the robustness of the results.ConclusionResults suggest that empagliflozin + SoC is cost-effective compared to sitagliptin + SoC and liraglutide + SoC at a willingness-to-pay threshold of 212,676RMB ($30,292)/QALY.

Objective: To compare the cost per responder of lixisenatide versus insulin glulisine once daily (basal-plus) and three times daily (basal-bolus) on top of basal insulin for the treatment of patien...

Discovery of pulsars is one of the main goals for large radio telescopes. The Five-hundred-meter Aperture Spherical radio Telescope (FAST), that incorporates an L-band 19-beam receiver with a system temperature of about 20~K, is the most sensitive radio telescope utilized for discovering pulsars. We designed the {\it snapshot} observation mode for a FAST key science project, the Galactic Plane Pulsar Snapshot (GPPS) survey, in which every four nearby pointings can observe {\it a cover} of a sky patch of 0.1575 square degrees through beam-switching of the L-band 19-beam receiver. The integration time for each pointing is 300 seconds so that the GPPS observations for a cover can be made in 21 minutes. The goal of the GPPS survey is to discover pulsars within the Galactic latitude of $\pm10^{\circ}$ from the Galactic plane, and the highest priority is given to the inner Galaxy within $\pm5^{\circ}$. Up to now, the GPPS survey has discovered 201 pulsars, including currently the faintest pulsars which cannot be detected by other telescopes, pulsars with extremely high dispersion measures (DMs) which challenge the currently widely used models for the Galactic electron density distribution, pulsars coincident with supernova remnants, 40 millisecond pulsars, 16 binary pulsars, some nulling and mode-changing pulsars and rotating radio transients (RRATs). The follow-up observations for confirmation of new pulsars have polarization-signals recorded for polarization profiles of the pulsars. Re-detection of previously known pulsars in the survey data also leads to significant improvements in parameters for 64 pulsars. The GPPS survey discoveries are published and will be updated at http://zmtt.bao.ac.cn/GPPS/ ., 38 pages, 22 figures. See http://www.raa-journal.org/docs/Supp/2021Newsonline.pdf for News and Views

The guideline is meant to standardize the principles, procedures, and methods for developing therapeutic drug monitoring (TDM) guidelines and promoting open, transparent, scientific, and credible TDM guidelines.Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society established guideline working groups, declared and managed conflicts of interest. The guideline working groups used the Delphi method to formulate the purpose and scope of the guidelines and questions in the PICO format, searched and synthesized evidence, and integrated with the current situation in China and TDM characteristics to preliminarily develop recommendations for the guideline for TDM guideline development in China. Through internal discussions of the guideline working groups and external peer review, the content was improved, and we eventually formulated a guideline suitable for guiding TDM-related guidelines.The guideline provides suggestions for problems to be identified and solved in the planning, development, publishing, and updating stages of TDM guidelines, including forming guideline working groups, planning guidelines, declaration and management of interests, formulating questions and selecting outcomes, preparing the planning proposal, evidence retrieval and synthesis, evidence assessment, developing recommendations, drafting guidelines, external review guidelines, publishing and disseminating guidelines, postevaluation of guidelines, and updating guidelines.This guideline can provide methodological guidance and reference for the development of TDM guidelines.

At present, SAR images from same source are widely used in the field of sea ice drift tracking. Due to the longer revisit time of homologous spaceborne satellites, only an average velocity can be determined. For longer time intervals, velocities due to short-duration events such as storms are lost. Synthetic Aperture Radar (SAR) images from different sources make it easy to construct image sequences with short time intervals. However, the resolution and noise level between non-homologous SAR image pairs often differ greatly. When there is a relatively large resolution difference between image pairs, the areal features between image pairs are very different, which increases the difficulty of feature registration. In this paper, a super-resolution reconstruction method is proposed to solve the problem of resolution difference between image pairs for sea ice drift. This method can significantly improve the quality of feature registration of image pairs from different SAR sensors. We demonstrate through several examples the effectiveness of the method in feature matching of large resolution difference images from different SAR sensors.

Aim: The study assesses the cost–effectiveness of empagliflozin versus glimepiride in patients with Type 2 diabetes and uncontrolled by metformin alone in China, based on the EMPA-REG H2H-SU trial. Materials & methods: A calibrated version of the IQVIA Core Diabetes Model was used. Cost of complications and utility were taken from literature. The Chinese healthcare system perspective and 5% discounting rates were applied. Results: Empagliflozin+metformin provides additional quality-adjusted life-years (0.317) driven by a reduction in the number of cardiovascular and renal events, for an additional cost of $1382 (CNY9703) compared with glimepiride+metformin. Conclusion: Empagliflozin is cost-effective treatment versus glimepiride applying a threshold of $30,290 (CNY212,676).

Peng Men,1,2 Tianbi Liu,1,3 Suodi Zhai1,2 1Department of Pharmacy, Peking University Third Hospital, Beijing, People’s Republic of China; 2Institute for Drug Evaluation, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Suodi Zhai Department of Pharmacy, Peking University Third Hospital, No. 49 North Huayuan Road, Haidian District, Beijing, People’s Republic of ChinaTel +86-13401169143Fax +86-10-82266686Email zhaisuodi@163.comPurpose: To evaluate the cost-utility of empagliflozin, in addition to best available standard care (BASC), for the treatment of adult patients with T2DM at high cardiovascular risk from the Chinese healthcare system perspective.Methods: A Microsoft Excel-based patient-level simulation model, based on the EMPA-REG OUTCOME trial data, was adapted and used to project individual’s clinical and economic outcomes over a lifetime horizon. The cost and utility values were derived from databases and published studies. Numbers and rates of diabetes-related events, life-years (LYs), quality-adjusted life-years (QALYs), costs (¥ 2019) as well as incremental cost-utility ratios (ICURs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results.Results: Compared with BASC, empagliflozin plus BASC was predicted to result in an additional 1.01 QALYs (8.05 QALYs vs 7.04 QALYs) at an incremental cost of ¥ 4002 per patient. The modeled ICUR was ¥ 3988 per QALY gained, which was considered highly cost-effective in China compared to both one and three times the GDP per capita in 2019 (¥ 70,892 and ¥ 212,676). The deterministic and probabilistic sensitivity analyses confirmed the robustness of base-case results.Conclusion: This is the first cost-utility analysis regarding the use of empagliflozin in patients with T2DM in China, the world’s most affected country by the T2DM pandemic. The economic evaluation suggests that empagliflozin added to BASC was estimated to be a highly value-for-money option for the treatment of adult patients with T2DM at high cardiovascular risk in the Chinese healthcare setting.Keywords: diabetes, China, sodium-glucose transporter 2 inhibitors, cost-effectiveness

Both amisulpride and olanzapine are leading treatments for schizophrenia in China. This study aimed to investigate the long-term cost-effectiveness of amisulpride and olanzapine in the treatment of schizophrenia in China.A decision-analytic Markov model was developed to simulate the lifetime clinical and economic outcomes of schizophrenia treatment from the healthcare payer perspective. The long-term costs and QALYs were estimated. Sensitivity analyses were performed to explore the impact of variance of parameters on the results.Treatment with amisulpride provided an effectiveness gain of 16.59 QALYs at an average cost of USD 25,884 whereas olanzapine resulted in 16.38 QALYs at a cost of USD 34,839 over a lifetime horizon. One-way sensitivity analysis suggested that the most sensitive variable was the unit cost of olanzapine. In a probabilistic sensitivity analysis based on a Monte Carlo simulation with a lifetime horizon, the probability of amisulpride being cost-effective was 99.8% at a willingness-to-pay threshold of USD 9,322, the GDP per capita in China 2018. A scenario analysis with updated olanzapine unit cost suggested an ICER of 7,857 USD/QALY.Amisulpride is likely to be a cost-effective option with increased effectiveness compared with olanzapine in the treatment of schizophrenia patients in China.

What is known and objective Thalidomide is used off-label for the treatment of inflammatory bowel disease (IBD) and not as a first-line treatment option. The instructions clearly state that thalidomide is contraindicated in children because its safety and effectiveness in children are unknown. In this article, we review the efficacy and safety of thalidomide as a treatment for IBD in children and adolescents. Methods We searched PubMed, Embase, the Cochrane Library, CNKI, WanFang Data, CBM database [from the date of database establishment to June 2019] and clinical trials [systematic review and meta-analysis, randomized controlled trials (RCTs), cohort studies, case-control studies and case series studies] for studies concerning the use of thalidomide as a treatment for IBD in children and adolescents. Results and discussion Seven studies (two RCTs and five case series), which included 134 children and adolescents (32 with ulcerative colitis, 102 with Crohn's disease), met the inclusion criteria. The included studies showed that the clinical remission rate of thalidomide was 44%-100% and the steroid tapering rate was 50%-100% in children and adolescents with refractory IBD. Peripheral neuropathy was the most common major adverse reaction, and it appeared to be cumulative dose-dependent. What is new and conclusion Thalidomide as a treatment for refractory IBD in children and adolescents can improve clinical remission and achieve longer-term maintenance of remission. Peripheral neuropathy is the main adverse drug reaction, and it can be monitored and prevented. It is necessary to fully communicate with parents and obtain informed consent before using this drug.

Background Amisulpride was introduced into China in 2010 as a second-generation atypical antipsychotic, while olanzapine has been on the market since 1999 as one of the leading treatments for schizophrenia in China. Since more Chinese patients are gaining access to amisulpride, the study aims to compare the efficacy, safety, and costs between amisulpride and olanzapine for schizophrenia treatment in China. Methods PubMed, Embase, the Cochrane library, China National Knowledge Infrastructure (CNKI) and WanFang database were systematically searched for randomized controlled trials (RCTs) up to July 2018. The Cochrane Risk of Bias tool was utilized to assess the quality of included studies. A meta-analysis was performed to compare the efficacy and safety of amisulpride and olanzapine, followed by a cost-minimization analysis using local drug and medical costs reported in China. Results Twenty RCTs with 2000 patients were included in the systematic review. There were no significant differences between amisulpride and olanzapine on efficacy measures based on scores from the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Brief Psychiatric Rating Scale and the Clinical Global Impressions-Severity or Improvement. For safety outcomes, amisulpride was associated with lower fasting blood glucose and less abnormal liver functions as well as significantly lower risks of weight gain, constipation, and somnolence; olanzapine was associated with significantly lower risks of insomnia and lactation/amenorrhea/sexual hormone disorder. No significant differences were found in risks of extrapyramidal symptoms (EPS), tremor, akathisia, abnormal corrected QT interval. Cost-minimization analysis showed that amisulpride was likely to be a cost-saving alternative in China, with potential savings of 1358 Chinese Yuan (CNY) per patient for a three-month schizophrenia treatment compared with olanzapine. Conclusion As the first meta-analysis and cost-minimization analysis comparing the efficacy, safety and cost of amisulpride and olanzapine within a Chinese setting, the study suggests that amisulpride may be an effective, well-tolerated, and cost-saving antipsychotic drug alternative in China.

In this study, we carried out a survey on organic-rich mudstones of Wufeng-Longmaxi formations in the frontal margin of Dabashan orogenic belt where geological structure is complex, aiming to investigate the shale gas enrichment condition and their major controlling factors. Methods including optical microscope observation, Scanning Electron Microscopy (SEM), organic geochemistry and tests of porosity, permeability, gas-bearing property, and Specific Surface Area have been applied in this study. Based on these comprehensive information collected from both the field and the laboratory, the general geological characteristics and distribution of organic-rich mudstones of Wufeng-Longmaxi formations are summarized. In the Late Ordovician-Early Silurian epoch, organic-rich mudstones were probably deposited in the continental shelf, with the thicknesses ranging from 31.5 to 156.4 m in the frontal margin of Dabashan orogenic belt, and the averaged value of total organic carbon in these mudstones varies from 2.43 to 5.17 wt% in different localities. Values of BET specific surface area range from 1.57 to 29.15 m2/g. Thermal maturity is high because Ro values vary from 1.20 to 2.58% in this region. The mineral composition, i.e., low clay mineral content (16.14–27.88%) and relatively high brittle mineral content (larger than 72.12%), is proper for future fracturing. Although the permeability and porosity values are relatively low, respectively 0.0001–0.0472 × 10−3μm2 and 0.36–3.51% in average, they are still higher than the lower limit of favorable condition of shale gas accumulation. Based on the shale gas evaluation and exploration experience conducted in this geologically complex area, we suggest that the shale gas generation conditions are good in the Dabashan area, but the preservation conditions are quite different from place to place in the tectonically complex area. In general, the preservation conditions are of the utmost importance for shale gas enrichment in Dabashan area. A comparison of failed to the successful cases of exploration wells in the frontal margin of Dabashan suggests that relatively stable box-shaped anticlines, like Tianba and Manyue anticlines, are beneficial for shale gas storage. Information obtained from this study can be used as a good reference for shale gas reservoir evaluation and the selection of shale gas Sweet Spots in further study of this region. Furthermore, the research conducted in this area provides useful experience for shale gas exploration in the tectonically complex region in the world.

Despite extensive use of statins, patients with hypercholesterolemia, especially homozygous familial hypercholesterolemia (HoFH), do not achieve recommended targets of low-density lipoprotein cholesterol (LDL-C). There is an urgent need for novel options that could reduce proatherogenic lipoprotein cholesterol levels. Lomitapide, a microsomal triglyceride transport protein (MTP) inhibitor, was approved three years ago as an orphan drug for the treatment of patients with HoFH. Our aim was to systematically evaluate the efficacy and safety of lomitapide and to provide guidance for clinicians. We searched the PubMed, Embase, and Cochrane library databases and ClinicalTrials.gov to identify valid studies published before 31 October 2016 that included lomitapide-treated patients who did or did not undergo lipid-lowering therapy. We assessed the quality of different studies. Data were extracted and evaluated for quality by two reviewers. Studies reporting lomitapide therapy included one randomized controlled trial, three single-arm studies, and five case reports. In patients with HoFH, lomitapide reduced levels of LDL-C, total cholesterol, apolipoprotein B, and triglycerides with or without other lipid-lowering therapy, including apheresis. In non-HoFH patients with moderate hypercholesterolemia and hypertriglyceridemia, lomitapide also showed favorable effects on changes in LDL-C and triglycerides. However, both HoFH and non-HoFH patients experienced a reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1). The most common adverse event was gastrointestinal disorder, and others included liver transaminase elevation and hepatic fat accumulation. Long-term use of lomitapide was associated with an increased risk of progressing to steatohepatitis and fibrosis. Lomitapide improved most lipid parameters but not HDL-C or ApoA-1 in patients with HoFH and in non-HoFH patients, and gastrointestinal disorders were the most common adverse event. The possible benefits of lomitapide should be further evaluated and viewed against its possible long-term side effects.

Shale gas exploration in the Upper Yangtze Basin has been conducted for over ten years. The successful drillings in the region suggest that well-planned geological survey and reservoir evaluation are indispensable for the success of these drillings. In this study, the shale gas potential of Late Ordovician to Early Silurian mudstones/shales of the Wufeng–Longmaxi formations in the Upper Yangtze Basin was evaluated. First, all of the available geochemical and petrological data from Late Ordovician to Early Silurian mudstones/shales in the region were compiled. Distributional patterns of total organic carbon (TOC) values, thickness, thermal maturity, and burial depth of organic-rich mudstones/shales from the targeted formations were then analyzed. Our results show that TOC values range from 1.20 to 5.12%; Ro values range from 1.92 to 2.86%; porosity varies from 0.77 to 9.2%; permeability varies from 0.015 to 1.99 md; the composition of quartz group of mineral component ranges from 18 to 85%, 59% in average; and clay mineral component ranges from 7 to 56%, 31% in average. Finally, based on these comprehensive analysis, three areas with great potential, that is, Luzhou-Xishui, western Chongqing, and Wulong-Shizhu, were selected as targets for further shale gas exploration and exploitation.

Background: Previous studies have preliminarily identified the non-inferior efficacy for reducing skeletal-related event (SRE) rates between de-escalated (Q12w) and standard (Q3-4w) bone-targeting agents therapy in malignant tumor patients with bone metastases. In this study, we aim to make further efforts to analyze whether the de-escalated bisphosphonates (BPs) strategy is a suitable option by comprehensively retrieving and synthesizing state-of-the-art evidence. Methods: An extensive electronic search for randomized controlled trials (RCTs) comparing a BPs standard strategy with the de-escalated one in patients with bone metastases was performed up to June 2018. Outcomes of interest were general and found individual types of SRE, skeletal morbidity rate (SMR), bone pain, bone turnover biomarkers and adverse events (AEs). Continuous and dichotomous outcomes were summarized by the weighted mean difference (WMD) and risk ratio (RR), respectively, with 95% confidence intervals (CIs). Results: A total of eight studies, representing six unique trials (involving 3114 patients), were included. Pooled results indicated comparable efficacy on general SRE (RR 0.99, 95% CI 0.87–1.12; P = 0.86; I2 = 0%) and SMR (WMD 0.00, 95% CI −0.02 −0.03; P = 0.81; I2 = 0%). However, the rate of surgery involving bones was significantly higher in de-escalated group than standard group (RR 1.92, 95% CI 1.17–3.15; P = 0.01; I2 = 0%) among individual types of SRE. Several trials also demonstrated increased levels of C-terminal or N-terminal telopeptide in de-escalated group. Meta-analyses for gastrointestinal disorders, dizziness and back pain showed significant reductions by 27% (RR 0.73, 95% CI 0.57–0.94; P = 0.01; I2 = 0%), 48% (RR 0.52 95% CI 0.32–0.86; P = 0.01; I2 = 0%), and 29% (RR 0.71, 0.51–0.99; P = 0.04; I2 = 0%), respectively, compared to the standard therapy. Conclusion: For malignant tumor patients with bone metastases, a de-escalated BPs strategy is proved to have a better safety profile compared to standard dosing. Although the efficacy is generally comparable on SRE and SMR between the two dosing regimens, trials with long duration and large sample sizes are still warranted to make a solid judgment.

Aims To evaluate the comparative efficacy and safety of lixisenatide combined with basal insulin (BI) vs intensive premix insulin (premix), BI plus prandial insulin with the main meal (basal-plus) or progressively covering all meals (basal-bolus) in patients with type 2 diabetes mellitus (T2DM) inadequately controlled by BI, and the long-term cost-effectiveness of lixisenatide from a Chinese healthcare system perspective. Materials and methods Randomized controlled trials (RCTs) published between 1998 and 2018 were systematically searched. The clinical efficacy and safety of each treatment were compared by network meta-analysis (NMA). The IQVIA CORE Diabetes Model was used to estimate the lifetime quality-adjusted life-years (QALYs) and direct medical costs of patients treated with different strategies. Results Eight RCTs were finally included. Lixisenatide plus BI showed a similar reduction in HbA1c from baseline compared with premix, basal-plus and basal-bolus. There were significant differences in the change of body weight in favour of lixisenatide plus BI compared with the three insulin regimens. The risk of symptomatic hypoglycaemia of lixisenatide plus BI was significantly lower compared with premix and basal-bolus. Lixisenatide plus BI was cost-effective compared with premix, basal-plus and basal-bolus with incremental cost-effectiveness ratios of Chinese yuan (CNY) 87 219, 48 173 and 48 670 per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China. Conclusions Lixisenatide plus BI shows a similar HbA1c reduction compared with insulin regimens, accompanied by lower risk of hypoglycaemia and greater body weight reduction. It is a cost-effective treatment alternative for patients with T2DM inadequately controlled by BI in China.

During the Early Cambrian, the middle–upper Yangtze area of South China evolved to an open shelf with anoxic bottom waters prevailing in most places. Accumulated black shales in this area, named Niutitang Formation (Qiongzhusi Formation in some places), thus become the prospective resources for shale gas exploration and development. Based on compiled petrological and organic geochemistry data, and other information obtained by relevant laboratory tests and field investigation, we documented regional distributional patterns of Lower Cambrian organic-rich shales in the middle–upper Yangtze area according to their lateral extent, thickness, total organic carbon, thermal maturity and burial depth. This study also features the general reservoir properties of dark shales in this area. Together these results highlight several most favorable areas including Youyang-Xiushan-Huayuan, Suiyang-Daozhen-Dejiang, Shiqian-Sinan-Yinjiang, Jiangkou-Tongren-Songtao and Huangping-Shibing for shale gas exploration.

Objective To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice. Methods Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software. Results A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes. Conclusion The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.

Objective To evaluate the comparative efficacy and safety of saxagliptin for type 2 diabetes (T2D). Methods A systematic search of PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov and two Chinese databases for randomized controlled trials (RCTs) comparing saxagliptin with placebo or active comparators was performed up to July 2017. A complementary search was done to cover literature until March 2018. For continuous data, estimates were pooled using inverse variance methodology to calculate weighted mean differences (WMDs). Dichotomous data were presented as Mantel-Haenzel risk ratios (RRs). Results Thirty-nine references of 30 RCTs involving 29,938 patients were analyzed. Compared with placebo, saxagliptin significantly reduced glycated hemoglobin (HbA1c, WMD -0.52%, 95% CI -0.60 to -0.44) and fasting plasma glucose (WMD -13.78 mg/dL, 95% CI -15.31 to -12.25), and increased the proportion of patients achieving HbA1c

Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 μM in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2.1 μM in in vitro assay. The molecular docking studies suggested the interaction modes of SMS1 inhibitors and PC with the active site of SMS1. Site-directed mutagenesis validated the involvement of residues Arg342 and Tyr338 in enzymatic sphingomyelin production. The discovery of SAPA derivatives as a novel class of SMS1 inhibitors would advance the development of more effective SMS1 inhibitors.