Stacking Ensemble of Disproportionality Indicators for Adverse Vaccine Reactions Detection-An Empirical Study on Predicting Adverse Reactions of COVID-19 Vaccines.

Vaccine safety is a critical issue for public health, which has recently become more crucial than ever since COVID-19 started to spread worldwide in 2020. Many COVID-19 vaccines have been developed and used without following the traditional three clinical trial stages. Instead, most COVID-19 vaccines were approved through emergency use approval (EUA) within one year, significantly raising the risk of rare and severe adverse events. Reporting systems like the Vaccine Adverse Event Reporting System (VAERS) have been established worldwide to detect unknown and severe adverse reactions as early as possible. Although experts and researchers have been working hard to find ways to detect adverse vaccine event (AVE) signals from VAERS data, most of the contemporary methods are statistical methods based on measuring the disproportionality between vaccine-induced events and non-vaccine-induced events. This paper proposes a novel ensemble AVE detection method, which adopts a stacking ensemble of various disproportionality indicators, fusing dual-scale contingency values measured in single and cumulative yearly duration, and embraces the concept of feature concatenation. Experiments conducted on US VAERS data to predict AVE caused by COVID-19 vaccines show that our proposed method is effective. We observed that: (1) Stacking ensemble of various disproportionality indicators is superior to any single disproportionality indicator and voting ensemble method; (2) Fusing dual-scale contingency values and feature concatenation brings synergy to our proposed stacking ensemble AVE detection. Compared to the best disproportionality metric in this study, our top-performing ensemble version exhibited a 34% improvement in accuracy, 71% in precision, 29% in recall, and 77% in F-measure, with a slight decrease (8%) in specificity.

Evidence and Potential Mechanisms of Traditional Chinese Medicine for the Adjuvant Treatment of Coronary Heart Disease in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Traditional Chinese medicine (TCM) has long been used to treat diabetes mellitus and angina. It has also gained widespread clinical applications in China as a common adjuvant treatment. Although there is high-quality evidence that TCM is effective in regulating glucose and lipid metabolism, the cardiovascular protective effect of TCM in the treatment of diabetes mellitus has not been fully elucidated, especially in patients with both diabetes mellitus and coronary heart disease (CHD). We systematically assessed the efficacy and safety of TCM for the adjuvant treatment of patients with CHD and diabetes mellitus and examined the pharmacological effects and potential mechanisms of TCM medication/herbs on diabetes mellitus with CHD. We found that TCM could improve the control effect of conventional treatment on cardiac function, hemorheology, blood glucose, blood lipid, and inflammation, thus reducing the frequency of angina and the incidence of cardiovascular events and all-cause mortality. These findings indicate that TCM may be used as a complementary approach for patients with diabetes mellitus and CHD. Nevertheless, more rigorously designed randomized controlled trials and long-term evaluations are needed to support these findings.

The Potential Roles of Artemisinin and Its Derivatives in the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a global public health problem. Studies on T2DM prevention and treatment mostly focus on discovering therapeutic drugs. Artemisinin and its derivatives were originally used as antimalarial treatments. In recent years, the roles of artemisinins in T2DM have attracted much attention. Artemisinin treatments not only attenuate insulin resistance and restore islet ß-cell function in T2DM but also have potential therapeutic effects on diabetic complications, including diabetic kidney disease, cognitive impairment, diabetic retinopathy, and diabetic cardiovascular disease. Many in vitro and in vivo experiments have confirmed the therapeutic utility of artemisinin and its derivatives on T2DM, but no article has systematically demonstrated the specific role artemisinin plays in the treatment of T2DM. This review summarizes the potential therapeutic effects and mechanism of artemisinin and its derivatives in T2DM and associated complications, providing a reference for subsequent related research.

Effects of Calcium Sulfate Combined with Platelet-rich Plasma on Restoration of Long Bone Defect in Rabbits.

BACKGROUND: The treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration. METHODS: A radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study. RESULTS: The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87%) and positive control (52.21 ± 4.53%) groups were significantly greater than those in the CS group (12.34 ± 2.17%) and PRP group (16.52 ± 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 ± 4.10%) was significantly greater than that of the CS group (20.10 ± 3.70%) or PRP group (25.10 ± 2.10%) (P < 0.001). CONCLUSION: CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength.

[Hsa-miR-654-5p regulates osteogenic differentiation of human bone marrow mesenchymal stem cells by repressing bone morphogenetic protein 2].

OBJECTIVE: To study the effect of hsa-miR-654-5p in repressing bone morphogenetic protein 2 (BMP2) mRNA and protein in human bone marrow mesenchymal stem cells (hBMSCs), and explore its regulatory role in osteogenic differentiation of hBMSCs. METHODS: hBMSCs in the 4th passage were cultured for 16 h and transfected with hsa-miR-654-5p followed by further culture for 48 h. qRT-PCR and Western blotting were performed to detect the expressions of BMP2 mRNA and protein. Dual-luciferase?reporter gene assay was employed to examine the repression of the BMP2 gene. RESULTS: BMP2 mRNA and protein expressions were significantly down-regulated in hBMSCs with hsa-miR-654-5p overexpression. Dualluci-ferase reporter gene assay indicated that the predicted target site of BMP2 was repressed directly by hsa-miR-654-5p, but this repression did not occur at the mutant predicted target site of BMP2. CONCLUSION: hsa-miR-654-5p can directly repress the mRNA and protein expressions of BMP2 by binding to a specific target site. The changes in hsa-miR-654-5p can play an important role in osteogenic differentiation regulation of hBMSCs.

[New research progress on atrophic nonunion].

Occurance of atrophic nonunion is a complex process. Previous studies suggested that atrophic nonunion was mainly due to lack of blood supply of fracture fragments, but recent studies found that blood supply was not deficiency in middle and late stages, indicating that decreased osteogenic factors and blood supply in early stages might play an important role in morbidity. Current effective treatment measures for atrophic nonunion mainly include bone graft and fixation,physical therapy, local injection therapy. All-round preventive could reduce incidence of atrophic nonunion. Atrophic nonunion is still a troublesome complication of fractures in orthopaedics, and more attention should be paid for its effective prevention and treatment. The paper summarized recent original articles about atrophic nonunion and reviewed the occurrence mechanisms, diagnosis, prevention and treatment measures of this disease.

[Restoration of segmental bone defect by calcium sulfate pellet: experiment with rabbit].

OBJECTIVE: To compare the effects of different calcium sulfate pellets made by different methods in treating segmental defect of bone. METHODS: Eighty New Zealand white rabbits underwent cutting off a segment in the middle part of radius so as to establish models of radial segmental defect, and than were divided into 4 groups: Group A as control group, Group B with calcium sulfate pellet made by routine method implanted into the defect, Group C with chitosan coated pressed calcium sulfate pellet implanted into the defect, and Group D with chitosan coated pressed calcium sulfate pellet combined with recombinant human bone morphogenetic protein (rhBMP)-2 implanted into the defect: X-ray photography was done every 4 weeks to observe the new bone formation. Four, 8, and 12 weeks 5 rabbits from each group were killed. The defect segments with parts of normal bone at both ends were cut off to undergo fluorescence microscopy and biomechanic three point bending test. RESULTS: X-ray photography and histological examination showed that new bone formation of cortex and reconstruction of marrow cavity were seen in Groups D and C, especially in Group D. The new bone mineralization rate of Group D was significantly higher than that of Group C (P<0.05) which was significantly higher than that of Group B (P<0.01). The anti-bending strength ratio of Group D was (47.5%+/-2.1%, significantly higher than that of Group C [(39.6+/-1.7)%, F=125.3, P<0.01], and the anti-bending strength ratios of Groups D and C were both significantly higher than those of Groups B and A [(23.6+/-3.3)% and (21.3+/-2.7)%]. CONCLUSION: Chitosan coated pressed calcium sulfate pellet shows relatively higher anti-bending strength and slightly slower resorption that closely coincide with the growth rate of new bone. It can be used to restore segmental bone defect, and particularly when combined with rhBMP-2.

[Experimental study on preparation of decellularized artery vascular graft matrix and explantation of carotid artery allografts].

OBJECTIVE: To set up a new process to access the preparation of decellularized artery grafts. And to evaluate the feasibility of decellularized artery allografts was evaluated. METHODS: This study compared the effects of four extraction chemicals [1% t-octyl-phenoxypolyethoxyethanol (Triton X-100), 1% tri (n-butyl) phosphate (TnBP), and 1% sodium dodecyl sulfate (SDS) and trypsin (0.125, 0.25%) on thoracic artery vascular for 24 h (except trypsin for 2 h). At the base of it, a four-step process, including hypotonic, hypertonic solutions and combining with 1% Triton X-100 and 1% SDS detergents, were performed in rabbit thoracic artery vascular. Histological examination, tensile tests and expanding-burst tests were done on the samples. The decellularized carotid artery allografts were transplanted in other rabbits. RESULTS: Treatment with 1% SDS or 1% Triton X-100 for 24 h could remove most cells with retention of near normal structure. A four-step process could remove all cells with the extracellular matrix well conserved. The pulling mechanical properties and burst pressure of decellularized carotid artery were similar to the control. The decellularized carotid artery allografts (diameter of 2 mm) were patent at explanting up to 2 months. CONCLUSIONS: The acellular artery vascular graft matrix is well prepared with four-step process including detergents, such as TritonX-100, SDS without compromising the graft structure or mechanical properties significantly. The carotid artery allografts (diameter of 2 mm) decellularized by the process are patent at explanting up to 2 months.

[Experimental study on repair of articular cartilage defect in large area with chondrocytes cultured on fascia].

OBJECTIVE: To study the biological characteristic and potential of chondrocytes grafting cultured on fascia in repairing large defect of articular cartilage in rabbits. METHODS: Chondrocytes of young rabbits were isolated and sub-cultured on fascia. The large defect of articular cartilage was repaired by grafts of freeze-preserved and fresh chondrocytes cultured on fascia, and free chondrocytes respectively; the biological characteristic and metabolism were evaluated by macroscopic, histological and immunohistochemical observations, autoradiography method and the measurement of nitric oxide content 6, 12, 24 weeks after grafting. RESULTS: The chondrocytes cultured on fascia maintained normal growth feature and metabolism, and there was no damage to chondrocytes after cryopreservation; the repaired cartilage was similar to the normal cartilage in cellular morphology and biological characteristics. CONCLUSION: Chondrocytes could be cultured normally on fascia, which could be used as an ideal carrier of chondrocytes.