Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

The impact of acupuncture combined with acupoint catgut embedding on simple obesity: A systematic review and meta-analysis.

BACKGROUND: Obesity is a widespread chronic metabolic disease that significantly impairs quality of life. Studies have demonstrated the efficacy of both acupuncture and acupoint catgut embedding (ACE) in the management of obesity. However, the superiority of acupuncture combined with ACE over acupuncture alone remains a subject of controversy. This study aims to elucidate this controversy and provide robust clinical evidence. METHODS: A comprehensive search of relevant literature from the initiation to July 2022 was carried out in 8 databases (PubMed, EMBASE, Cochrane database, Web of Science, CBM Database, CNKI, Wan-fang Database, and VIP Database). We included randomized controlled trials (RCTs) that investigated the treatment of simple obesity using acupuncture paired with ACE, with acupuncture alone as the control group. The pooled outcomes included body mass index (BMI), body weight (BW), %BF, waist circumference (WC), hip circumferences (HC), waist-to-hip ratio (WHR), therapeutic effective rate (TER), and adverse events. Two independent reviewers performed screening (using EndNote X9) and quality assessment (using the Cochrane Risk of Bias tool) for the included studies. with the software RevMan 5.3 was used to perform pooling of effect sizes. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: A total of 20 trials involving 15 datasets (1616 participants) were included. The findings demonstrated significant improvements in outcome measures when acupuncture was combined with ACE, compared with acupuncture alone (BMI: MD = -1.49 kg/m2, 95% confidence interval [CI] = -1.93 to -1.04, P < .01; BW: MD = -2.38, 95% CI = -3.86 to -0.89, P < .01; %BF: MD = -2.19, 95% CI = -3.23 to -1.15, P < .01; WC: MD = -2.01, 95% CI = -3.66 to -0.35, P < .05; HC: MD = -0.83, 95% CI = -1.64 to -0.02, P < .05; WHR: MD = -0.02, 95% CI = -0.03 to -0.01, P < .01; TER: OR = 2.68, 95% CI = 1.93-3.74, P < .01). Adverse effects were reported in 4 studies. CONCLUSION SUBSECTIONS: The results of this meta-analysis indicate that acupuncture combined with ACE is superior to acupuncture alone in the treatment of obesity, which is supported by the subgroup analysis. The assessment of efficacy may have been influenced by variations in study quality, potentially amplifying the observed effects. RCTs with larger sample sizes and improved methodological quality are needed to enhance the validity of the findings.

Smoking, alcohol and coffee consumption and risk of low back pain: a Mendelian randomization study.

PURPOSE: Low back pain (LBP) is a common health problem in the global population. This study aims to assess whether smoking initiation, alcohol consumption, and coffee consumption are causally with an increased risk of LBP. METHODS: A two-sample Mendelian Randomization (MR) study was designed, based on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with genome-wide significance level (P < 5.0 × 10-8) were selected as instrumental variables for each exposure. Standard inverse-variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods, which relax some IV assumptions, were used for sensitivity analysis. RESULTS: Genetically predicted smoking initiation was causally associated with higher odds of LBP. The pooled OR of LBP using IVW method was 1.36 (95%CI 1.22 1.52; P = 6.0 × 10-8) for one SD increase in the prevalence of smoking initiation, which was supported by the weighted median method (OR: 1.41, 95%CI 1.22, 1.64; P = 5.7 × 10-6). Sensitivity analysis confirmed the robustness of pooled OR of LBP. There was no evidence to suggest a causal effect of alcohol and coffee consumption on LBP. The pooled ORs of LBP were 1.36 (95%CI 0.94, 1.97; P = 0.10) for alcohol consumption and 1.00 (95%CI 0.99, 1.00; P = 0.17) for coffee consumption, respectively. CONCLUSION: Smoking is casually associated with an increased risk of LBP. Smoking control should be recommended in LBP patients to avoid worsening the disease. The safety of LBP with moderate alcohol and coffee consumption merits more study.

Tuo-Min-Ding-Chuan Decoction Alleviate Ovalbumin-Induced Allergic Asthma by Inhibiting Mast Cell Degranulation and Down-Regulating the Differential Expression Proteins.

Allergic asthma is a stubborn chronic inflammatory disease, and is considered a co-result of various immune cells, especially mast cells, eosinophils and T lymphocytes. At present, the treatment methods of allergic asthma are limited and the side effects are obvious. Traditional Chinese medicine has been used to treat diseases for thousands of years in China. One such example is the treatment of allergic asthma, which take the characteristics of less adverse reactions and obvious curative effect. Tuo-Min-Ding-Chuan Decoction (TMDCD) is a traditional Chinese medicine compound for the treatment of allergic asthma optimized from Ma-Xing-Gan-Shi Decoction (MXGSD), which was put forward in Treatise on Febrile Diseases by Zhang Zhongjing in the Eastern Han Dynasty. The compound shows a significant clinical effect, but the mechanism of its influence on the immune system is still unclear. The purpose of this study was to observe whether TMDCD could alleviate the symptoms of ovalbumin (OVA) challenged allergic asthma mice, and to explore its immune regulatory mechanism, especially on mast cell (MC) degranulation. The results showed TMDCD could not only reduce the airway hyperresponsiveness (AHR), inflammatory cell infiltration and mucus secretion in the lung tissue of OVA challenged mice, but also decrease the levels of total IgE, OVA-specific IgE, histamine and LTC4 in serum. We found that TMDCD can downregulate the expression of Fractalkine, Tryptase ε, IL-25, CCL19, MCP-1, OX40L, Axl, CCL22, CD30, G-CSF, E-selectin, OPN, CCL5, P-selectin, Gas6, TSLP in OVA challenged mice serum by using mouse cytokines antibody array. It has been reported in some literatures that these differentially expressed proteins are related to the occurrence of allergic asthma, such as tryptase ε, MCP-1, CCL5, etc. can be released by MC. And the results of in vitro experiments showed that TMDCD inhibited the degranulation of RBL-2H3 cells stimulated by DNP-IgE/BSA. Taken together, we made the conclusion that TMDCD could reduce the infiltration of inflammatory cells in lung tissue and alleviate airway remodeling in mice with allergic asthma, showed the effects of anti-inflammatory and antiasthmatic. TMDCD could also reduce the levels of IgE, histamine, LTC4, Tryptase ε, and other MC related proteins in the serum of allergic asthma mice, and the in vitro experiments showed that TMDCD could inhibit IgE mediated degranulation and histamine release of RBL-2H3 cells, proved its anti allergic effect.