Effect of ezetimibe-statin combination therapy vs. statin monotherapy on coronary atheroma phenotype and lumen stenosis in patients with coronary artery disease: a meta-analysis and trial sequential analysis.

Background: Evidence indicates that the addition of ezetimibe to statin therapy reduces cardiovascular events. However, the impact of ezetimibe-statin combination therapy on coronary plaque regression, plaque stabilization, and diameter stenosis remains a matter of controversy. Methods: We performed electronic searches in PubMed, Web of Knowledge, and the Cochrane Central Register of Controlled Trials to identify eligible trials assessing the effects of ezetimibe-statin combination therapy versus statin monotherapy reporting at least one outcome among total atheroma volume (TAV), minimum fibrous cap thickness (FCT), lumen volume (LV), and lumen area (LA) derived from intravascular imaging modalities of intravascular ultrasound (IVUS) and optical coherence tomography (OCT). We used the random-effects model and performed trial sequential analysis (TSA) during this meta-analysis. Results: Eleven articles with a total of 926 individuals (460 in the dual-lipid-lowering therapy group and 466 in the statin monotherapy group) were included in the final meta-analysis. Compared to statin monotherapy, ezetimibe-statin combination therapy was associated with significantly decreased TAV [WMD = -3.17, 95% CI (-5.42 to -0.92), and p = 0.006], with no effect on the LV of the coronary artery [WMD = -0.52, 95% CI (-2.24 to 1.21), and p = 0.56], the LA of the coronary artery [WMD = 0.16, 95% CI (-0.10-0.42), and p = 0.22], or minimum FCT thickness [WMD = 19.11, 95%CI (-12.76-50.97)]. Conclusion: In patients with coronary artery disease, ezetimibe-statin combination therapy resulted in a significant regression in TAV compared to statin monotherapy, whereas no overall improvements of minimum FCT or lumenal stenosis were observed.

Growing attention on the toxicity of Chinese herbal medicine: a bibliometric analysis from 2013 to 2022.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM's toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade. Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations. Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019-2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology. Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

Fibrolipomatous Hamartoma of the Median Nerve: A Clinical Report of One Case and Review of the Literature.

BACKGROUND: The ultrasound imaging findings and clinical treatment procedure of a case of fibrolipomatous hamartoma of the median nerve are reported in this paper. The disease diagnosis was mainly dependent on magnetic resonance, and rarely described by ultrasound. This paper introduces the imaging manifestations of median neurofibromatoid hamartoma under ultrasound. CASE PRESENTATION: This case is a middle-aged female with pituitary adenoma. Fibrolipomatous hamartoma, as a rare benign fibrofatty tumor, is characterized by the slow proliferation of mature adipocytes and fibrous tissue around and inside the peripheral nerves, eventually leading to the fusiform enlargement of nerve fiber bundles. DISSCUSSION: This paper discusses the value and application of color doppler ultrasound in the diagnosis of FLH to provide a reference for the clinical diagnosis and treatment of this disease in the future and reviews the literature on this disease. CONCLUSION: Because fibrolipomatous hamartoma is very rare, it is very important to improve the understanding and diagnosis of this disease.

Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review.

INTRODUCTION: Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed. OBJECTIVE: To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up. MATERIALS AND METHODS: We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis. RESULTS: Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation. CONCLUSION: This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.

Exploration of severe Covid-19 associated risk factor in China: Meta-analysis of current evidence.

AIM: This meta-analysis aimed to explore potential risk factors for severe Covid-19. METHODS: We systemically and comprehensively retrieved the eligible study evaluating clinical differences between severe vs non-severe Covid-19. Main effect sizes were demographic characteristics, comorbidities, signs and symptoms, laboratory findings as well as radiological features of chest CT. RESULTS: A total of 2566 Covid-19 people (771 in the severe group and 1795 in the non-severe group) from 14 studies were eligible for this meta-analysis. It was demonstrated that older age and males were more likely to have severe Covid-19. Patients with underlying comorbidities, such as hypertension, diabetes, heart disease and COPD were significantly more susceptible to severe Covid-19. Patients with dyspnoea were more likely to be severely ill. Depressed total lymphocytes were observed in this article. Meanwhile, although reticulation (30.8%), intrathoracic lymph node enlargement (20.5%) and pleural effusions (30.8%) were relatively infrequent, meta-analysis revealed that patients with these presentations in chest CT were associated with increased risk of severe Covid-19. CONCLUSIONS: There are significant differences in clinical characteristics between the severe and non-severe Covid-19 patients. Many factors are related to the severity of the disease, which can help clinicians to differentiate severe patients from non-severe patients.

Losartan Protects Podocytes against High Glucose-induced Injury by Inhibiting B7-1 Expression.

The role of B7-1 in podocyte injury has received increasing attention. The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease (DKD) by regulating B7-1 and the underlying mechanisms. Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks. Biochemical changes in blood and urine were analyzed. Kidneys were isolated for electron microscopy, immunofluorescence, real-time quantitative PCR (RT-PCR), and Western blot analysis. Immortalized mouse podocyte cells were cultured in normal or high glucose medium in the presence or absence of losartan for 48 h, and then the cells were collected for immunofluorescence, PCR, Western blotting and monolayer permeability detection. The phosphatidylinositol 3-kinase (PI3K) 110α subunit and angiotensin II type 1 receptor (AT1R) plasmids were transfected into podocytes, respectively, and then Western blotting was performed to assess the expression of B7-1 protein. The results showed that losartan ameliorated podocyte structure and function in the rat model of DKD, and reduced the expression of B7-1 protein. Overexpression of PI3K 110α subunit in podocytes attenuated the inhibitory effect of losartan on B7-1 expression in high glucose-stimulated podocytes. The expression of B7-1 was significantly increased by overexpression of AT1R and significantly reduced by blocking PI3K 110α subunit. We conclude that losartan protects podocytes against high glucose-induced injury by inhibiting AT1R-mediated B7-1 expression. This effect is dependent on the AT1R-PI3K 110α subunit pathway.

Association of the Expression Levels of Long-Chain Noncoding RNA TUG1 and Its Gene Polymorphisms with Knee Osteoarthritis.

Objective: To study the association of the expression levels of long noncoding RNA Taurine-upregulated gene 1 (lncRNA TUG1) and TUG1 polymorphisms with knee osteoarthritis (KOA). Materials and Methods: A total of 255 KOA patients and 255 controls from May 2017 to December 2019 were selected for the study. Sanger sequencing was conducted to detect the genotypes of the TUG1 rs5749201, rs7284767, and rs886471 loci in all study subjects. Unconditional logistic regression analysis was used to calculate odds ratios and 95% confidence intervals, and the associations between the TUG1 rs574901, rs7284767 and rs886471 loci and KOA risk were analyzed. Multifactor dimensionality reduction was used to analyze the interactions among alleles at the three TUG1 loci examined. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of TUG1 lncRNA in plasma. Results: A total of 255 KOA patients and 255 control subjects completed the study. After adjusting for the factors of gender, age, body mass index, smoking history, drinking history, and family history, we found that the carriers of the A allele of the TUG1 rs5749201 locus were 1.36 times more likely to develop KOA than the carriers of the T allele (95% confidence interval [CI] = 1.05-1.75, p = 0.02); the G allele of the rs7284767 locus was a protective factor for KOA (odds ratio [OR] = 0.71, 95% CI = 0.54-0.92, p = 0.01); and the allelic variation at rs886471 G > T led to an increased risk of KOA by 2.34 times (95% CI = 1.53-3.57, p < 0.01). We also found that the GAG haplotype for the three loci was significantly associated with the increased risk of KOA (OR = 2.77, 95% CI = 1.67-4.57, p < 0.01). There was no correlation found between the TUG1 rs886471, rs5749201, and rs7284767 single nucleotide polymorphisms loci and the severity of KOA. The allelic variation at TUG1 rs5749201 T > A, rs886471 T > G were associated with decreased levels of TUG1 lncRNA in the plasma of the subjects, while the allelic variation at rs7284767 A > G was associated with increased levels of TUG1 lncRNA in plasma (p = 0.01, p < 0.01, p < 0.01). Conclusion: Plasma TUG1 lncRNA levels and loci at the TUG1 rs5749201, rs7284767, and rs886471 loci are associated with KOA risk.

Comparison of detection rate of 16 sampling methods for respiratory viruses: a Bayesian network meta-analysis of clinical data and systematic review.

BACKGROUND: Respiratory viruses (RVs) is a common cause of illness in people of all ages, at present, different types of sampling methods are available for respiratory viral diagnosis. However, the diversity of available sampling methods and the limited direct comparisons in randomised controlled trials (RCTs) make decision-making difficult. We did a network meta-analysis, which accounted for both direct and indirect comparisons, to determine the detection rate of different sampling methods for RVs. METHODS: Relevant articles were retrieved comprehensively by searching the online databases of PubMed, Embase and Cochrane published before 25 March 2020. With the help of R V.3.6.3 software and 'GeMTC V.0.8.2' package, network meta-analysis was performed within a Bayesian framework. Node-splitting method and I2 test combined leverage graphs and Gelman-Rubin-Brooks plots were conducted to evaluate the model's accuracy. The rank probabilities in direct and cumulative rank plots were also incorporated to rank the corresponding sampling methods for overall and specific virus. RESULTS: 16 sampling methods with 54 438 samples from 57 literatures were ultimately involved in this study. The model indicated good consistency and convergence but high heterogeneity, hence, random-effect analysis was applied. The top three sampling methods for RVs were nasopharyngeal wash (NPW), mid-turbinate swab (MTS) and nasopharyngeal swab (NPS). Despite certain differences, the results of virus-specific subanalysis were basically consistent with RVs: MTS, NPW and NPS for influenza; MTS, NPS and NPW for influenza-a and b; saliva, NPW and NPS for rhinovirus and parainfluenza; NPW, MTS and nasopharyngeal aspirate for respiratory syncytial virus; saliva, NPW and MTS for adenovirus and sputum; MTS and NPS for coronavirus. CONCLUSION: This network meta-analysis provides supporting evidences that NPW, MTS and NPS have higher diagnostic value regarding RVs infection, moreover, particular preferred methods should be considered in terms of specific virus pandemic. Of course, subsequent RCTs with larger samples are required to validate our findings.

Association of PAR-2 Gene Polymorphisms with the Inflammatory Response and Susceptibility to Knee Osteoarthritis in the Chinese Han Population.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of protease-activated receptor 2 (PAR-2) and the susceptibility to knee osteoarthritis (KOA) and synovial expression of inflammatory factors in the Chinese Han population. METHODS: Three hundred fifty KOA patients (KOA group) and 345 healthy volunteers (control group) were recruited for the study. Five milliliters of venous blood was taken from each subject to detect the PAR-2 rs1529505, rs631465, and rs2242991 locus genotypes. The expression of PAR-2 mRNA in the synovial tissue and the levels of matrix metalloproteinase (MMP-1), MMP-9, interleukin (IL)-6, and IL-1ß in the joint effusion were detected in 205 KOA patients who had undergone joint replacement surgery. RESULTS: The PAR-2 rs1529505 T allele and the rs2242991 G allele carriers had a higher risk of KOA (p < 0.001). The severity of KOA in patients with the PAR-2 rs1529505 and rs2242991 mutations were higher than in the wild-type controls (p < 0.05). The expression levels of the PAR-2 mRNA in wild types, heterozygotes, and homozygotes of the rs1529505 and rs2242991 loci increased in turn (p < 0.001). The levels of MMP-1, MMP-9, IL-6, and IL-1ß in the synovial fluid of the PAR-2 rs1529505 and rs2242991 locus mutants were distinctly higher than those with the wild-type alleles (p < 0.01). There was no correlation between the rs631465 SNP and susceptibility to KOA, severity of KOA, nor levels of PAR-2 mRNA, MMP-1, MMP-9, IL-6, and IL-1ß. CONCLUSIONS: The PAR-2 SNPs rs1529505 and rs2242991 are associated with the susceptibility to KOA. KOA is more severe in patients harboring the T and G alleles of these two SNPs, respectively. The levels of inflammatory factors in synovial tissue and blood are higher than those in wild-type patients.

SND1 promotes the proliferation of osteosarcoma cells by upregulating COX­2/PGE2 expression via activation of NF­κB.

Osteosarcoma is the most frequent primary bone tumor. Staphylococcal nuclease domain­containing 1 (SND1) is a multifunctional protein that plays important roles in tumor development and progression. Overexpression of SND1 has been found in several malignancies, however, its expression and function in osteosarcoma is largely unknown. In the present study, we firstly examined the expression of SND1 in 12 pairs of osteosarcoma and healthy bones by immunoblotting and real time­PCR. The results revealed that osteosarcoma tissues expressed significantly high SND1 mRNA and protein expression compared to normal bone tissues. Next, we stably overexpressed SND1 ORF in MG­63 cells and further defined the biological function of SND1 in osteosarcoma by flow cytometry, cell proliferation and in vivo assays. We found that SND1 overexpression significantly promoted cell proliferation and tumor growth in vitro and in vivo. Furthermore, the non­targeted metabolic profiling, ELISA and luciferase reporter assays were performed on stable overexpressing cells and blood samples to elucidate the underlying mechanisms of SND1­mediated oncogenic features. The results revealed that SND1 increased the production of arachidonic acid PGE2. The serum PGE2 expression level had a significant positive association with the SND1 mRNA expression level in osteosarcoma tissues. The SND1 overexpression­stimulated cell proliferation was enhanced by exogenous addition of PGE2. Additionally, we found that SND1 upregulated PGE2 expression through the NF­κB/cyclooxygenase­2 (COX­2) pathway. In summary, our findings revealed the mechanisms of SND1 involvement in osteosarcoma tumor development, and support the targeting of SND1 as a new anti­tumor strategy for patients with osteosarcoma. In addition, SND1 may act as a potential biomarker of the therapeutic strategies utilizing COX­2 inhibitors.

Efficacy and safety of empagliflozin for type 2 diabetes mellitus: Meta-analysis of randomized controlled trials.

BACKGROUND: This study was designed to evaluate the efficiency and tolerability of empagliflozin (EMPA) as monotherapy or add-on to existing therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: Randomized controlled trials (RCTs) comparing efficacy and safety of EMPA vs placebo or EMPA plus other antidiabetes drugs vs placebo plus other oral antidiabetes drugs (OADs) in T2DM were recruited from electronic database Pubmed, Web of Knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL), supplemented by a hand search of the reference lists of selected articles. Main effect sizes were change from baseline on glycemia control, body weight, blood pressure, and complications (i.e., incidence of urinary and genital tract infections, and morbidity of hypoglycemia and hyperglycemia). Random-effects model was used to account for clinical or methodologic heterogeneity across studies. RESULTS: Fifteen RCTs with a total number of 7891 individuals (5374 in EMPA group and 2517 in control group) were suitable for this meta-analysis. The results demonstrated that significant improvements in glycemia control, body weight, and blood pressure were associated with EMPA application (i.e., monotherapy and add-on therapy) in patient with T2DM when compared with placebo. Meanwhile, EMPA 10 and 20 mg improved glycemia, body weight, and blood pressure control for patients with T2DM. There was no significant difference in incidence of hypoglycemia and urinary tract infections across EMPA and placebo group. Significant reduced risk of hyperglycemia was revealed in EMPA group vs placebo (risk ratio: 0.34, 95%confidence interval: 0.23-0.49, P < .00001), except in patients on background insulin therapy. However, increased risk of genital infection was noted across EMPA vs placebo (risk ratio: 2.59, 95% confidence interval: 1.80-3.71, P < .00001). CONCLUSION: Our evidence supports the application of EMPA in treatment of patients with T2DM who are obesity or at risk of weight gain.

Combined analysis of gene expression, miRNA expression and DNA methylation profiles of osteosarcoma.

Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we conducted a combined analysis of three types of microarray datasets (gene expression, microRNA (miRNA) expression and DNA methylation) from the Gene Expression Omnibus (GEO). The differential expression genes (DEGs) and miRNAs (DEMI) were screened out via the limma package and differential methylation sites (DMS) were identified by the IMA package. Enriched functions of DEGs and genes contained DMS (DEMs) were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Besides, miRNA-gene regulation network was obtained based on the pairs of involved DEMIs and overlapping genes between DEMs and DEGs and visualized through Cytoscape software. A total of 583 DEGs and 1051 DMS (corresponding to 827 DEMs) were identified and 56 overlaps were obtained. As expected, most of the expression and methylation profiles of the overlaps exhibited significant negative correlation. The DEGs were mainly enriched in the biological processes related to inflammatory/immune response, cell proliferation, while DEMs were involved in the regulation of gene expression, tissue/organ development. Based on the correlation and network analysis, some novel targets were identified for OS and many known biomarkers were proved in this study, which would be helpful in its early diagnosis and treatment.

Is unilateral kyphoplasty as effective and safe as bilateral kyphoplasties for osteoporotic vertebral compression fractures? A meta-analysis.

BACKGROUND: An osteoporotic vertebral compression fracture is a common condition in elderly people, especially women. The percutaneous kyphoplasty is an effective treatment for osteoporotic vertebral compression fractures. Controversy remains regarding whether a unilateral or a bilateral approach is superior, and to our knowledge, there have been no large studies comparing these two approaches, therefore a meta-analysis synthesizing the data on this question is warranted. QUESTIONS/PURPOSES: We asked the following questions: (1) Is there evidence to suggest a benefit in clinical outcome as assessed by the VAS and Oswestry Disability Index of a unilateral kyphoplasty or bilateral kyphoplasties? (2) Are the complications associated with the two approaches different? (3) Do the procedures result in different kyphosis angle reduction or anterior vertebral height restoration? (4) Is the surgical time for the procedures different? METHODS: We searched the Cochrane Library, PubMed MEDLINE, EMBASE, Web of Knowledge MEDLINE (January 1980 to June 2013), and reference lists of eligible prospective studies. The levels of the evidence and recommendations were assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Five studies encompassing 253 patients met the inclusion criteria. RESULTS: The short- and long-term clinical outcomes as assessed by the VAS and Oswestry Disability Index showed no differences between unilateral and bilateral kyphoplasties (p = 0.41, p = 0.60 for VAS; p = 0.10, p = 0.36 for Oswestry Disability Index). There were no differences in complications such as cement leakage and adjacent vertebral fractures associated with the two approaches (p = 0.43 and p = 0.95). The kyphosis angle reduction and anterior vertebral height restoration showed no difference between the two approaches (p = 0.34 and p = 0.46). The unilateral approach was shorter in terms of surgical time (mean difference, -24.98; p < 0.0001). The overall GRADE system evidence quality was very low, with only high evidence for operation time, which lessens our confidence in recommendations. CONCLUSIONS: Unilateral and bilateral percutaneous kyphoplasties appear to be safe and effective for treating osteoporotic vertebral compression fractures. No clinically important differences were found between them. Considering less operation time and less cost, we suggest that a unilateral percutaneous kyphoplasty is advantageous, but because of the poor quality of the evidence, high-quality randomized controlled trials are required to resolve this issue.

Percutaneous vertebroplasty versus balloon kyphoplasty for treatment of osteoporotic vertebral compression fracture: a meta-analysis of randomised and non-randomised controlled trials.

PURPOSE: There is still debate over whether vertebroplasty (VP) or kyphoplasty (KP) is superior for the treatment of osteoporosis vertebral compression fractures (VCFs). We performed a systematic review and meta-analysis of randomised and non-randomised controlled trials comparing VP with KP to reach a relatively conclusive answer. METHODS: We searched computerised databases comparing efficacy and safety of VP and KP in osteoporotic fractures. These trials reported pain relief (Visual Analogue Scale), disability (Oswestry disability score) and complications (i.e., cement leakage, incident fractures) as the primary outcome. RESULTS: Eight studies involving 848 patients were identified. The outcome showed that VP is more effective in the short-term (no more than seven days) pain relief. Kyphoplasty had a superior capability for intermediate-term (around three months) functional improvement. As for long-term pain relief and functional improvement, there is no significant difference between these two interventions. Consistently, both interventions have similar risk for subsequent fracture and cement leakage. CONCLUSION: Thus considering the higher cost of the KP procedure, we recommend VP over KP for the treatment of osteoporotic VCFs.