Objective To investigate changes in coagulation function and inflammation levels during sepsis.Methods A rat model of sepsis was established using the multiple infection sepsis model(MIM)based on cecal ligation and puncture.Forty-eight male Sprague-Dawley rats were assigned randomly to the following groups:control group,sham group,4 h sepsis group,8 h sepsis group,12 h sepsis group,and 16 h sepsis group(n=8 per group).Inflammatory markers and coagulation-related indicators were measured by enzyme-linked immunosorbent assay and coagulation analysis.Results(1)Lipopolysaccharide(LPS)and interleukin-6(IL-6)levels were significantly higher in the model rats at all time points compared with the sham group(P＜0.001).LPS and IL-6 levels increased gradually with disease progression,with no further changes in LPS after 12 hours.(2)Prothrombin time(PT)was significantly prolonged in the middle and late stages of the sepsis model,starting from 8,compared with the sham group(P＜0.01).(3)Partially activated prothrombin time(APTT)time was significantly prolonged in the 8,12,and 16 h groups compared with the sham group(P＜0.05,P＜0.01).APTT gradually lengthened from 8 h,but approached control levels thereafter.(4)Fibrinogen(Fbg)content was significantly higher in all sepsis groups,except for the 8 h group,compared with the sham group(P＜0.01).(5)Fibrin degradation products(FDP)differed significantly between the control and sham groups(P＜0.01),but not between the sham and sepsis groups.(6)Antithrombin-Ⅲ(AT-Ⅲ)levels decreased significantly throughout each stage of sepsis progression compared with the sham group(P＜0.01),and AT-Ⅲ showed a downward trend with the course of disease,with significant differences among the 4,8,and 16 h groups.Conclusions The MIM rat model can reflect the development of inflammatory and blood coagulation disorders and their relationship during the course of sepsis,and may thus provide a good foundation for further research into the disease course of sepsis.

Randomized controlled trials (RCT) have long been considered the gold standard for assessing clinical efficacy. However, RCT are inappropriate for some diseases due to related ethical issues and costs, such as rare diseases that are seriously life-threatening but without adequate treatment. Using real world data (RWD) as external control for RCT could make recruitment less complicated and reduce time and cost. This paper introduces common application scenarios, data sources, study design, basic principles, and statistical methods of RWD as an external control based on the latest guidelines related to RWD and combined with our team's previous research experience. This study could provide references for scholars and sponsors who want to conduct RWD research.

Boao Lecheng International Medical Tourism Pilot Area is the only administrative area in China where the pilot application of real-world data is performed. Based on the special healthcare policy in Boao Lecheng, conducting real-world data study to provide real-world evidence for the clinical evaluations and approvals of innovated medical products has become an important field that supports the reform of China's evaluation and approval system of medical products. Trustworthy real-world evidence needs to rely on both high-quality real-world data and reasonable and rigorous study designs. Based on the real-world data research guidelines and specifications issued by relevant academic research and regulatory authorities both at home and abroad, combined with the special policy environment of Boao Lecheng and previous practice experience, this paper summarizes the study designs of real world data in Boao Lecheng and discusses the key considerations of different study design in the context of special healthcare policies in Boao Lecheng in order to provide reference for the further study of real-world data.

OBJECTIVE To explore the risk signals of Fluocinolone acetonide intravitreal implants and promote safe and rational drug use for patients. METHODS Based on the data from the Hainan Province Franchised Drug Adverse Reaction Monitoring Subsystem （hereinafter referred to as the “Franchised Drug Monitoring System”） and the FDA Adverse Event Reporting System （FAERS）， the adverse drug reaction （ADR）/adverse drug event （ADE） reports of Fluocinolone acetonide intravitreal implants were coded by using system organ classification and preferred terminology， and relevant patient information was collected. Risk signal mining was carried out by using the reporting odds ratio （ROR） method and the comprehensive standards method of the UK Medicines and Healthcare Products Regulatory Agency （hereinafter referred to as the “MHRA method”）. RESULTS Among the 72 reports of Fluocinolone acetonide intravitreal implants received by the Franchised Drug Monitoring System， the ratio of male to female was 1∶1.4， the patient’s age was mainly distributed between 18 and 64 years old； ADR/ADE affected 5 systemic organs， with eye organ diseases accounting for 87.7%； among them， there were 9 new and general ADR reports （12.5%） and 4 severe ADR reports （5.6%）； ROR method and MHRA method both identified three risk signals： cataracts， glaucoma， and high intraocular pressure. Among the 244 reports received by the FAERS database， the ratio of male to female was 1∶1.5； ADR/ADE damage affected 10 systemic organs， with 46.1% suffering from various injuries， poisoning， and operational complications， and 32.0% suffering from product problems； there were 20 severe ADR reports （8.2%）； ROR method and MHRA method both identified 19 risk signals， including implantation complications， medication system issues， etc. CONCLUSIONS When using Fluocinolone acetonide intravitreal implants in clinical practice， in addition to paying attention to eye ADR/ADE such as high intraocular pressure， cataracts， and glaucoma， attention should also be paid to the potential risks caused by ADE due to product quality and unreasonable use.

Objective:To accurately estimate the health burden and corresponding economic loss attributed to PM 2.5 pollution in the Beijing-Tianjin-Hebei (BTH) area in China in 2015. Method:By using satellite-retrieved PM 2.5 concentration data and population data provided by NASA (the spatial resolution was 1 km×1 km), this study estimated excess mortality attributed to long-term PM 2.5 exposure in BTH area in 2015 based on Global Exposure Mortality Model (GEMM). Besides, Value of Statistic Life (VSL) method was used to evaluate the corresponding health economic loss. Result:In BTH area, the population-weighted average PM 2.5 concentration during 2012-2014 was 46.25 μg/m 3, and 56.6% of total population lived in the area where annual average PM 2.5 concentration exceeded Grade Ⅱ of National Ambient Air Quality Standard in China (35 μg/m 3); The PM 2.5-related premature deaths amounted to 193.8 thousand (95 %CI: 140.9 thousand-233.3 thousand), Beijing, Tianjin, Baoding, Shijiazhuang, and Handan were the top five cities with high incidences of PM 2.5-related premature deaths; The corresponding health economic loss was about 35.934 billion (95 %CI: 26.099 billion - 43.255 billion) RMB, accounting for 0.70% (95 %CI: 0.51%-0.85%) of the area’s GDP in 2015, Beijing, Tianjin, Baoding, Shijiazhuang, and Cangzhou were the top five cities with high health economic loss. Conclusions:PM 2.5 pollution has caused severe disease and economic burden in BTH area. Its spatial distribution suggested that it is particularly necessary to develop the air pollution prevention and control policies for key cities.

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.

CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.

BACKGROUND: Stroke is the leading cause of death in China, and predicting the stroke burden could provide essential information guiding the setting of medium- and long-term health policies and priorities. The study aimed to project trends associated with stroke burden in China through 2050, not only in terms of incidence and mortality but also for prevalence and disability-adjusted life years (DALYs). METHODS: Data on stroke rates in incidence, prevalence, deaths, and DALYs in China between 1990 and 2019 were obtained from a recent Global Burden of Disease study. Demographic-specific trends in rates over time were estimated using three models: the loglinear model, the Lee-Carter model, and a functional time series model. The mean absolute percentage error and the root mean squared error were used for model selection. Projections up to 2050 were estimated using the best fitting model. United Nations population data were used to project the absolute numbers through 2050. RESULTS: From 2019 to 2050, the crude rates for all measures of the stroke burden are projected to increase continuously among both men and women. We project that compared with those in 2019, the incidence, prevalence, deaths, and DALYs because of stroke in China in 2050 will increase by 55.58%, 119.16%, 72.15%, and 20.04%, respectively; the corresponding increases in number were 2.19, 34.27, 1.58, and 9.21 million. The age-standardized rate is projected to substantially decline for incidence (8.94%), death (40.37%), and DALYs (43.47%), but the age-standardized prevalence rate is predicted to increase by 10.82%. By 2050, the burden of stroke among the population aged ≥65 years will increase significantly: by 104.70% for incidence, by 218.48% for prevalence, by 100.00% for death, and by 58.93% for DALYs. CONCLUSIONS With the aging population in China increasing over the next three decades, the burden of stroke will be markedly increased. Continuous efforts are needed to improve stroke health care and secondary prevention, especially for older adults.
Male ; Humans ; Female ; Aged ; Cost of Illness ; Quality-Adjusted Life Years ; Stroke/epidemiology* ; Incidence ; Prevalence ; China/epidemiology*