In recent years, researchers, pharmaceutical companies, and political makers gradually using more real-world data (RWD) to produce real-world evidence (RWE) for policy-making. A research team of Harvard University launched the RCT DUPLICATE project in 2018, aiming to replicate 30 randomized controlled trials using the medical claims database in order to explore methods for quantifying the efficacy-effectiveness gap and explain its potential sources, to enhance the credibility of the RWE. This paper reviews the background of RCT DUPLICATE Initiative, highlights the research purposes, research design and implementation process of the RCT DUPLICATE Initiative, to help domestic scholars better understand the scope and application value of RWE.
Humans ; Randomized Controlled Trials as Topic ; Cognition ; Databases, Factual ; Research Personnel ; Universities

With the promotion and application of big medical data, non-interventional real-world evidence (RWE) has been used by regulators to assess the effectiveness of medical products. This paper briefly introduces the latest progress and research results of the RCT DUPLICATE Initiative launched by the research team of Harvard University in 2018 and summarizes relevant research experience based on the characteristics of China's medical service to provide inspiration and reference for domestic scholars to conduct related RWE research in the future.
Humans ; Randomized Controlled Trials as Topic ; Cognition ; Big Data ; Universities

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin

Objective:To explore the effects of Tiaoren Tongdu Acupuncture on motor function and corticospinal tract (CST) remodeling after cerebral infarction. Methods:From February, 2017 to December, 2020, 54 patients with cerebral infarction were randomly divided into control group (n = 27) and acupuncture group (n = 27), each group was divided into subgroups 1, 2 and 3 according to the impairment of corticospinal tract, with nine cases for each subgroup. All the patients received routine medicine, while the acupuncture group received Tiaoren Tongdu Acupuncture, for four weeks. They were assessed with Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI) before and after treatment, and scanned with diffusion tensor imaging and diffusion tensor tractography, to obtain the fractional anisotropy (FA) and the bilateral FA ratio (rFA). Results:The scores of FMA and MBI, and FA and rFA increased in both groups (t > 2.841, P < 0.05) after treatment, and increased more in the acupuncture group than in the control group (t > 2.140, P < 0.05). Conclusion:Tiaoren Tongdu Acupuncture can promote the recovery of CST to improve motor function for patients with cerebral infarction.

【Objective】 To establish and evaluate a nephelometric assay for the determination of immunoglobulin A (IgA) residues in human intravenous immunoglobulin(IVIG). 【Methods】 BN ProSpec^© automatic protein analyzer and its supporting immunoglobulin A determination kit (nephelometry) produced by German Siemens and the national standard of human IgA were used to establish the nephelometric assay to determine IgA residue in test products and verify the methodology. The test products include IVIG (pH4) prepared by low-temperature ethanol protein separation process and a novel IVIG prepared by chromatography. 【Results】 The average deviation of three calibration curves for IgA residues determination by the nephelometric assay were 1.08%, 0.95% and 1.54%,, and the three deviations of the quality control were 4.00%, -2.30% and -0.20%, respectively, which indicated good calibration and quality control. In the specificity test, the average recovery rates of IgA for reference substance 1 containing 100g/L maltose and reference substance 2 containing 20g/L glycine were 102.7% and 105.8%, respectively. The relative standard deviation (RSD) values of the repeatability tests of the two test products were 3.9% and 1.9%, and the RSD values of the intermediate precision test were 3.6% and 2.3%, respectively.The difference values at each time point in the durability test of test products′ storage time were all less than 10%, and the RSD values of the two test products in the durability test of kits of different batches were 2.8% and 2.2%, respectively. In the accuracy test, the average recovery rates of IVIG (pH4) added to the standard were 94.2%, 101.7% and 96.2%, respectively, and the average recovery rates of the novel IVIG added to the standard were 102.8%, 106.3% and 99.7%, respectively. The average recovery rate of the limit quantification test was 101.0%, and the RSD was 4.0%. 【Conclusion】 Nephelometric assay has the advantages of strong specificity, high precision and accuracy, good repeatability, simple and rapid operation, and automation, and can be used for the determination of IgA residue in IVIG (pH4) and novel IVIG products.

Objective To explore the expressions of Caveolin-1 and Ki-67 in esophageal squamous cell carcinoma tissues and discuss the clinical significances.Methods The expressions of Caveolin-1 and Ki-67 in 110 specimens of esophageal squamous cell carcinoma tissues (treatment group) and 15 specimens of normal esophageal tissues (control group) were detected by immunohistochemistry technique.The correlation between their positive expression and the elinieopathologie features were analyzed.Results The positive rates of Caveolin-1 were 47.62％ (10/21 cases),70.91％ (39/55 cases),94.11％ (32/34 cases) in low,middle,and high differentiation in treatment group,had significant difference with that in control group,which was 33.33％ (5/15 cases,P ＜ 0.05).The positive rates of Ki-67 were 52.38％ (11/21 cases),85.45％ (47/55 cases),97.06％ (33/34 cases) in low,middle,and high differentiation in treatment group,had significant difference with that in control group,which was 20.00％ (3/15 cases,P ＜0.05).Expression of Caveolin-1 was positively related with expression of Ki-67 in esophageal squamous cell carcinoma tissues(r =0.545,P ＜ 0.001).The positive expression of Caveolin-1 and Ki-67 were correlated with differentiation degree,tumor-node-metastasis (TNM) stage,lymph node metastasis,and liver metastasis(all P ＜0.05).Conclusions The expression levels of Caveolin-1 and Ki-67 are high in esophageal squamous cell carcinoma tissues,which have correlation with differentiation degree,TNM stage,lymph node metastasis,and liver metastasis.

OBJECTIVETo investigate single nucleotide polymorphisms(SNPs) and haplotypes of interleukin-18(IL-18) gene associated with the susceptibility to colorectal cancer(CRC).

METHODSTwo SNPs of IL-18 gene promoter -137G/C and -607C/A in 170 patients with CRC and 160 healthy controls matched by age and sex in a Chinese population were analyzed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) strategy. Frequency of haplotypes and linkage disequilibrium of IL-18 gene in different groups were analyzed by SHEsis programs.

RESULTSThe distributions of IL-18 gene -607C/A polymorphism did not differ between CRC patients and healthy controls, but IL-18 gene -137G/C polymorphism was significantly different(P<0.05). The relative risk of C allele for CRC was 1.814 times of the G allele (OR=1.814,95% CI:1.246-2.642). Consistent with the results of the genotyping analyses, IL-18 -137G/C and -607C/A polymorphisms showed strong linkage disequilibrium(|D'|=0.945), frequency of the -137C/-607A haplotype in patients with CRC was significantly higher than that in healthy controls(P<0.05). The -137C/-607A haplotype was associated with a significantly increased risk of CRC(OR=1.637, 95% CI:1.100-2.437).

CONCLUSIONSIL-18 gene -137G/C polymorphism and -137C/-607A haplotype are associated with CRC. -137C allele may be an important genetic susceptibility gene for CRC.

Adult ; Case-Control Studies ; Colorectal Neoplasms ; genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Interleukin-18 ; genetics ; Male ; Middle Aged ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVEFabricate series of the controllable degradation coral-hydroxyapatite.

METHODSThe natural coral undergo a chemical reaction with (NH4)2 HPO4 at high temperature and pressure for different time-lengths. After getting the products, the components and the special structures were analyzed. Observe the biologic degradation of the reaction products and analyze the metal elements and their contents. Haemolysis tests, cytotoxity tests and bone compatibility tests were performed to assess the biocompatibility of the products.

RESULTSWhen hydrothermal reactions happened under different conditions, the different gradients of CaCO3/hydroxyapatite materials were produced. These types of materials kept the characteristic of interconnected micro-porous network structures. A thin layer of compact material can be seen on the surface of its trabecula ultra-micro structure. The SCHA-200R has a good biocompatibility.

CONCLUSIONSGradient HA (SCHA-200R) materials can be formed by adjusting the same temperature, same pressure and different time-length of the reaction. This kind of gradient material keeps the quality of micro-porous network structures. The SCHA-200R is a potential candidate scaffold for bone tissue engineering.

Absorbable Implants ; Animals ; Anthozoa ; chemistry ; Bone Substitutes ; Durapatite ; chemical synthesis ; Male ; Materials Testing ; Rabbits ; Tissue Engineering ; methods

OBJECTIVETo compare the clinical and angiographic outcome in patients with type-II diabetes mellitus undergoing drug-eluting stent (DES) or bare-metal stent (BMS).

METHODSA total of 139 consecutive diabetic patients (114 males) with coronary disease who underwent successful elective percutaneous coronary intervention with DES (n = 83 with 151 lesions) or BMS (n = 56 with 70 lesions) on native coronary arteries from April 2004 to August 2005 at our institution were included in this study. All patients were treated according to guidelines and coronary angiography was repeated at 6 months post procedure in all patients. Aspirin (300 mg/d) and clopidogrel (75 mg/d) were administered till 6 months after the procedure.

RESULTSThere were 42.5% C type by ACC/AHA and 19.0% total occlusion lesions. The average stent length of each lesion was 26.53 +/- 14.72 mm, and mean reference diameter was 2.80 +/- 0.43 mm. Baseline characteristics were similar between DES and BMS groups except lower mean reference vessel diameter in DES than that of BMS group (2.71 +/- 0.41 mm vs. 2.98 +/- 0.53 mm, P < 0.001). The in stent restenosis rate at 6 months (10.6% vs. 38.6%, P < 0.001) and in-segment late loss (0.24 +/- 0.56 mm vs. 0.91 +/- 0.77 mm, P < 0.001) were significantly lower in DES group than those of BMS group. The target lesion revascularization (TLR) incidence was also significantly lower in DES group compared to BMS group (8.6% vs. 30.0%, P < 0.001). However, 4 late in-stent thrombosis were seen in DES group and none in BMS group of DES (P = 0.148).

CONCLUSIONDES implantation in patients with diabetes mellitus is associated with lower in-stent restenosis and TLR rates compared to BMS implantation 6 months after procedure and attention should be paid on late in-stent thrombosis after DES implantation.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; complications ; therapy ; Diabetes Mellitus, Type 2 ; complications ; therapy ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVECompare drug-eluting stent (DES) to bare-metal stent (BMS) in prognosis on treating diffuse coronary lesions and analysis risk factor of treating complex and diffuse lesions in PCI.

METHODS205 consecutive patients with complex and diffuse coronary lesions enrolled our hospital, who were treated with more than 25 mm long DES or BMS. We exclude unsuccessful operation and location. All patients received medical treatment by guideline, and aspirin 300 mg and clopidogrel 75 mg once daily were continued at 6 months after the procedure. The patients were followed up after 6 months.

RESULTSThe study population were consisted of 205 patients that there were 181 man, and 24 women, who got 382 stents for 227 target lesions in coronary. There were 93.8% C and 6.2% B2 ACC/AHA type lesion. There were 86.8% patients with binary or above vessel treated. The average reference vessel diameter was 2.88 +/- 0.43 mm. The average stent length of per lesion was 40.09 +/- 12.94 mm. There were 54.2% lesions treated with overlapping stent. There were not different between DES and BMS in patients baseline characteristics, but RVD of group DES less than of group BMS (2.80 +/- 0.37 mm, 3.10 +/- 0.48 mm, P = 0.005) in lesion baseline characteristics. After 6 months, restenosis rate in group DES was less than in group BMS (15.4%, 48.4%, P < 0.001). There were obvious superiority TVR of DES than of BMS (11.6%, 38.5%, P < 0.001). The rate of local restenosis in group of DES was higher than that in group of BMS (33.3%, 18.2%, P = 0.029). We analyzed the risk factors for diffuse lesion by a logistic regression model, the significant univariate clinical and angiographic predictors of restenosis were treating with overlapping stent (OR = 2.82, P = 0.017) and drug-eluting stent (OR = 5.71, P < 0.001).

CONCLUSIONSWe find that implantation of DES in patients with diffuse lesions in coronary is relatively more safe and associated with more good clinical outcomes, than of BMS.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Coronary Artery Disease ; diagnostic imaging ; therapy ; Coronary Restenosis ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Stents ; Treatment Outcome