The role and mechanism of tumor necrosis factor-alpha in alcohol-induced bone loss.

AIM: It is well known that alcohol can cause bone loss and that bone mineral density has an inverse relationship with bone marrow adipocyte (BMA). However, little is known about the mechanisms that link alcohol and bone loss, and existing studies lack data on BMA in alcohol-induced bone loss. Here, wild-type (WT) and tumor necrosis factor-alpha knockout (TNF-α KO) mice were used to examine the effects of alcohol on bone metabolism. METHODS: The effects of alcohol on bone metabolism were demonstrated in vivo by feeding WT and TNF-α KO mice with alcohol. The osteogenesis and adipogenesis of primary bone marrow stromal cells (BMSCs) derived from WT and TNF-α KO mice under alcohol intervention were compared in vitro. Tissue staining, cell staining, micro-CT, and quantitative RT-PCR were used to explore the potential mechanism. RESULTS: Alcohol induced trabecular bone loss, increased BMA, and promoted the mRNA expression of Adipoq, Fabp4, visfatin， Pparg, TNF-α, IL-1ß, and IL-6 in BMA in WT mice, but not in TNF-α KO mice. In addition, alcohol promoted BMSC adipogenesis and inhibited BMSC osteogenesis, while TNF-α knockout could restrain this situation. CONCLUSION: Our study demonstrated that alcohol may reduce bone mass by disrupting the balance of osteogenesis and adipogenesis in bone marrow, and TNF-α plays an important role in this process.

Gut microbiota and bone metabolism.

Osteoporosis is the most common metabolic skeletal disease. It is characterized by the deterioration of the skeletal microarchitecture and bone loss, leading to ostealgia, and even bone fractures. Accumulating evidence has indicated that there is an inextricable relationship between the gut microbiota (GM) and bone homeostasis involving host-microbiota crosstalk. Any perturbation of the GM can play an initiating and reinforcing role in disrupting the bone remodeling balance during the development of osteoporosis. Although the GM is known to influence bone metabolism, the mechanisms associated with these effects remain unclear. Herein, we review the current knowledge of how the GM affects bone metabolism in health and disease, summarize the correlation between pathogen-associated molecular patterns of GM structural components and bone metabolism, and discuss the potential mechanisms underlying how GM metabolites regulate bone turnover. Deciphering the complicated relationship between the GM and bone health will provide new insights into the prevention and treatment of osteoporosis.

Unveiling Latent Structure of Venture Capital Syndication Networks.

Venture capital (VC) is a form of private equity financing provided by VC institutions to startups with high growth potential due to innovative technology or novel business models but also high risks. To against uncertainties and benefit from mutual complementarity and sharing resources and information, making joint-investments with other VC institutions on the same startup are pervasive, which forms an ever-growing complex syndication network. Attaining objective classifications of VC institutions and revealing the latent structure of joint-investment behaviors between them can deepen our understanding of the VC industry and boost the healthy development of the market and economy. In this work, we devise an iterative Loubar method based on the Lorenz curve to make objective classification of VC institutions automatically, which does not require setting arbitrary thresholds and the number of categories. We further reveal distinct investment behaviors across categories, where the top-ranked group enters more industries and investment stages with a better performance. Through network embedding of joint investment relations, we unveil the existence of possible territories of top-ranked VC institutions, and the hidden structure of relations between VC institutions.

Identification of potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma.

BACKGROUND: This study aimed to identify potential crucial genes and construction of microRNA-mRNA negative regulatory networks in osteosarcoma by comprehensive bioinformatics analysis. METHODS: Data of gene expression profiles (GSE28424) and miRNA expression profiles (GSE28423) were downloaded from GEO database. The differentially expressed genes (DEGs) and miRNAs (DEMIs) were obtained by R Bioconductor packages. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. The relationships among the DEGs and module in PPI network were analyzed by plug-in NetworkAnalyzer and MCODE seperately. Through the TargetScan and comparing target genes with DEGs, the miRNA-mRNA regulation network was established. RESULTS: Totally 346 DEGs and 90 DEMIs were found to be differentially expressed. These DEGs were enriched in biological processes and KEGG pathway of inflammatory immune response. 25 genes in the PPI network were selected as hub genes. Top 10 hub genes were TYROBP, HLA-DRA, VWF, PPBP, SERPING1, HLA-DPA1, SERPINA1, KIF20A, FERMT3, HLA-E. PPI network of DEGs followed a pattern of power law network and met the characteristics of small-world network. MCODE analysis identified 4 clusters and the most significant cluster consisted of 11 nodes and 55 edges. SEPP1, CKS2, TCAP, BPI were identified as the seed genes in their own clusters, respectively. The miRNA-mRNA regulation network which was composed of 89 pairs was established. MiR-210 had the highest connectivity with 12 target genes. Among the predicted target of MiR-96, HLA-DPA1 and TYROBP were the hub genes. CONCLUSION: Our study indicated possible differentially expressed genes and miRNA, and microRNA-mRNA negative regulatory networks in osteosarcoma by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of osteosarcoma.

Impact of a Multidisciplinary Heart Failure Post-hospitalization Program on Heart Failure Readmission Rates.

BACKGROUND: Specialized chronic heart failure (HF) clinics have demonstrated significant reductions in readmissions. Limited evidence is available regarding HF clinics in the immediate post-discharge period. OBJECTIVE: To evaluate the effect of a multidisciplinary HF clinic on 90-day readmission rates and all-cause mortality in those recently discharged from a HF hospitalization. METHODS: In this retrospective cohort study, patients discharged with a primary HF diagnosis who attended the HF postdischarge clinic in 2010-2012 were compared with controls from 2009. During 6 clinic visits, patients were seen by a physician assistant, clinical pharmacist specialist, and case manager, with care overseen by a cardiologist. The program focused on optimizing therapy, identifying HF etiology/precipitating factors, medication titration, education, and medication adherence. The primary outcome was 90-day HF readmission. A multivariate Cox proportional hazards model was used to compare outcomes. RESULTS: Among the 277 patients (144 clinic, 133 control) in the study, 7.6% of patients in the clinic and 23.3% of patients in the control group were readmitted for HF within 90 days (aHR (adjusted hazard ratio) = 0.17; 95% CI = 0.07-0.41; P < 0.001; ARR (absolute risk reduction) = 15.7%; NNT (number needed to treat) = 7). Clinic patients had lower 90-day time-to-first HF readmission or all-cause mortality (9.0% vs 28.6%; aHR = 0.28; 95% CI = 0.06-0.31; P < 0.001; ARR = 19.6%; NNT = 6). CONCLUSIONS: The multidisciplinary HF posthospitalization outpatient program was associated with a significant reduction in 90-day HF readmissions in patients who were recently discharged from a HF hospitalization.

Impact of the ENHANCE trial on the use of ezetimibe in the United States and Canada.

BACKGROUND: We previously found that the use of ezetimibe increased rapidly with different patterns between the United States (US) and Canada prior to the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhance Atherosclerosis Regression (ENHANCE) trial, which was reported in January 2008, and failed to show that the drug slowed the progression of atherosclerosis. What is not known is how practice in the 2 countries changed after the ENHANCE trial. We examined ezetimibe use trends in the US and Canada before and after the reporting of the ENHANCE trial. METHODS: We conducted a population-based, retrospective, time-series analysis using the data collected by IMS Health in the US and CompuScript in Canada from January 1, 2002, to December 31, 2009. The main outcome measure was monthly number of prescriptions for ezetimibe-containing products. RESULTS: The monthly number of ezetimibe prescriptions/100,000 population rose from 6 to 1,082 in the US from November 2002 to January 2008, then significantly declined to 572/100,000 population by December 2009 after the release of the ENHANCE trial, a decrease of 47.1% (P < .001). In contrast, in Canada, use continuously rose from 2 to 495/100,000 population from June 2003 to December 2009 (P = .2). United States expenditures totaled $2.24 billion in 2009. CONCLUSIONS: Ezetimibe remains commonly used in both the US and Canada. Ezetimibe use has decreased in the US post-ENHANCE, whereas use has gradually but steadily increased in Canada. The diverging patterns of ezetimibe use in the US and Canada require further investigation, as they reveal that a common evidence base is eliciting very different utilization patterns in neighboring countries.

[Impact of lithocholic acid on the osteogenic and adipogenic differentiation balance of bone marrow mesenchymal stem cells].

Objective: To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods: Twelve 10-week-old SPF C57BL/6J female mice were randomly divided into an experimental group (undergoing bilateral ovariectomy) and a control group (only removing the same volume of adipose tissue around the ovaries), with 6 mice in each group. The body mass was measured every week after operation. After 4 weeks post-surgery, the weight of mouse uterus was measured, femur specimens of the mice were taken for micro-CT scanning and three-dimensional reconstruction to analyze changes in bone mass. Tibia specimens were taken for HE staining to calculate the number and area of bone marrow adipocytes in the marrow cavity area. ELISA was used to detect the expression of bone turnover markers in the serum. Liver samples were subjected to real-time fluorescence quantitative PCR (RT-qPCR) to detect the expression of key genes related to bile acid metabolism, including cyp7a1, cyp7b1, cyp8b1, and cyp27a1. BMSCs were isolated by centrifugation from 2 C57BL/6J female mice (10-week-old). The third-generation cells were exposed to 0, 1, 10, and 100 µmol/L LCA, following which cell viability was evaluated using the cell counting kit 8 assay. Subsequently, alkaline phosphatase (ALP) staining and oil red O staining were conducted after 7 days of osteogenic and adipogenic induction. RT-qPCR was employed to analyze the expressions of osteogenic-related genes, namely ALP, Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), as well as adipogenic-related genes including Adiponectin (Adipoq), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ (PPARγ). Results: Compared with the control group, the body mass of the mice in the experimental group increased, the uterus atrophied, the bone mass decreased, the bone marrow fat expanded, and the bone metabolism showed a high bone turnover state. RT-qPCR showed that the expressions of cyp7a1, cyp8b1, and cyp27a1, which were related to the key enzymes of bile acid metabolism in the liver, decreased significantly ( P<0.05), while the expression of cyp7b1 had no significant difference ( P>0.05). Intervention with LCA at concentrations of 1, 10, and 100 µmol/L did not demonstrate any apparent toxic effects on BMSCs. Furthermore, LCA inhibited the expressions of osteogenic-related genes (ALP, Runx2, and OCN) in a dose-dependent manner, resulting in a reduction in ALP staining positive area. Concurrently, LCA promoted the expressions of adipogenic-related genes (Adipoq, FABP4, and PPARγ), and an increase in oil red O staining positive area. Conclusion: After menopause, the metabolism of bile acids is altered, and secondary bile acid LCA interferes with the balance of osteogenic and adipogenic differentiation of BMSCs, thereby affecting bone remodelling.

The unique role of bone marrow adipose tissue in ovariectomy-induced bone loss in mice.

BACKGROUND: Accumulation of bone marrow adipose tissue (BMAT) is always seen in osteoporosis induced by estrogen deficiency. Herein, we aimed to investigate the mechanisms and consequences of this phenomenon by establishing a mouse model of osteoporosis caused by ovariectomy (OVX)-mimicked estrogen deficiency. METHODS: Micro-CT, osmium tetroxide staining, and histological analyses were performed to examine the changes in bone microstructure, BMAT and white adipose tissue (WAT) in OVX mice compared to sham mice. The osteogenesis and adipogenesis of primary bone marrow stromal cells (BMSCs) isolated from sham and OVX mice were compared in vitro. The molecular phenotypes of BMAT and WAT were determined and compared by quantitative PCR (qPCR). Bone marrow adipocyte-conditioned medium (BMA CM) was prepared from sham or OVX mice for coculture assays, and BMSCs or bone marrow monocytes/macrophages (BMMs) were isolated and subjected to osteoblast and osteoclast differentiation, respectively. Cell staining and qPCR were used to assess the effects of BMAT on bone metabolism. RESULTS: OVX-induced estrogen deficiency induced reductions in both cortical and trabecular bone mass along with an expansion of BMAT volume. At the cellular level, loss of estrogen inhibited BMSC osteogenesis and promoted BMSC adipogenesis, whereas addition of estradiol exerted the opposite effects. In response to estrogen deficiency, despite the common proinflammatory molecular phenotype observed in both fat depots, BMAT, unlike WAT, unexpectedly exhibited an increase in adipocyte differentiation and lipolytic activity as well as the maintenance of insulin sensitivity. Importantly, BMAT, but not WAT, presented increased mRNA levels of both BMP receptor inhibitors (Grem1, Chrdl1) and Rankl following OVX. In addition, treatment with BMA CM, especially from OVX mice, suppressed the osteoblast differentiation of BMSCs while favoring the osteoclast differentiation of BMMs. CONCLUSION: Our study illustrates that OVX-induced estrogen deficiency results in bone loss and BMAT expansion by triggering imbalance between the osteogenesis and adipogenesis of BMSCs. Furthermore, expanded BMAT, unlike typical WAT, may negatively regulate bone homeostasis through paracrine inhibition of osteoblast-mediated bone formation and promotion of osteoclast-mediated bone resorption.

Electroacupuncture promotes gastrointestinal function recovery in patients undergoing laparoscopic gastrectomy : a randomized controlled trial. / ç”µé’ˆä¿ƒè¿›è ¹è ”é•œèƒƒç™Œæ ¹æ²»æœ¯æ‚£è€ èƒƒè‚ åŠŸèƒ½æ¢å¤ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To explore the clinical effect of electroacupuncture (EA) on promoting gastrointestinal function recovery in patients undergoing laparoscopic gastrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic gastrectomy were randomly divided into an EA group (40 cases, 1 case was eliminated), a placebo EA (PEA) group (40 cases, 1 case dropped out) and a conventional treatment group (40 cases, 1 case dropped out). The patients in the conventional treatment group received perioperative routine treatment. On the basis of routine treatment, patients in the EA group and the PEA group were given electroacupuncture or placebo electroacupuncture stimulation at 24,48 and 72 h after anesthesia recovery. Bilateral Neiguan (PC 6), Zusanli (ST 36) and Shangjuxu (ST 37) were selected, and the electrodes of SDV-Z electroacupuncture instrument were connected to Zusanli (ST 36) and Shangjuxu (ST 37) on the same side respectively. Continuous wave was selected, the frequency was 5 Hz, and the needles were retained for 30 min each time. The postoperative gastrointestinal-2 ( GI-2 ) time, the incidence of grade A/B delayed gastric emptying were compared among the three groups, and the safety of acupuncture was evaluated. RESULTS: The GI-2 time of the EA group was significantly shorter than that of the PEA group and the conventional treatment group (P<0.05). The incidence of grade A and grade B of delayed gastric emptying in the EA group was lower than that in the PEA group and the conventional treatment group (P<0.05). No acupuncture-related adverse reactions occurred. CONCLUSIONS: EA can promote the recovery of gastrointestinal function in patients undergoing laparoscopic gastrectomy, and the treatment plan is safe, which is worthy of promotion and application into the enhanced recovery surgery program.

Grape seed extract prevents oestrogen deficiency-induced bone loss by modulating the gut microbiota and metabolites.

Proanthocyanidin-rich grape seed extract (GSE) has been shown to have the potential to protect bones, although the underlying mechanism remains unknown. The current study aims to explore GSE's preventive and therapeutic impact on bone loss induced by oestrogen deficiency and the underlying mechanism through the gut microbiota (GM) and metabolomic responses. In oestrogen-deficient ovariectomized (OVX) mice, GSE ameliorated bone loss by inhibiting the expansion of bone marrow adipose tissue (BMAT), restoring BMAT lipolysis and promoting bone formation. GSE regulated OVX-induced GM dysbiosis by reducing the abundance of opportunistic pathogenic bacteria, such as Alistipes, Turicibacter and Romboutsia, while elevating the abundance of beneficial bacteria, such as Bifidobacterium. The modified GM primarily impacted lipid and amino acid metabolism. Furthermore, the serum metabolites of GSE exhibited a significant enrichment in lipid metabolism. In summary, GSE shows potential as a functional food for preventing oestrogen deficiency-induced bone loss by modulating GM and metabolite-mediated lipid metabolism.

Electroacupuncture at ST36 modulates the intestinal microecology and may help repair the intestinal barrier in the rat model of severe acute pancreatitis.

Severe acute pancreatitis (SAP) onset and development are closely associated with intestinal barrier injury. Evidence from clinical practice and research has shown that electroacupuncture (EA) at the Zusanli (ST36) acupoint can improve intestinal barrier function and abdominal symptoms in patients with SAP; however, the specific mechanisms of action remain unclear. This study aimed to observe the changes in the intestinal microbiota and metabolites in SAP rats and to explore the effect of EA at ST36 on intestinal barrier injury in SAP rats. 16S rRNA gene sequencing combined with microbial diversity analysis, short-chain fatty acids (SCFAs)-targeted metabolomics, immunohistochemistry, immunofluorescence, western blotting, and other techniques were used to explore the mechanism of EA at bilateral ST36 acupoints on SAP-related intestinal barrier injury. Our results showed that EA at ST36 could repair intestinal barrier injury by modulating intestinal microecology, thereby reducing intestinal inflammation, restoring intestinal function, and ultimately alleviating the prognosis of SAP. Our study provides new insights into the mechanisms and treatment of intestinal barrier injury in patients with SAP from the perspectives of microbiota and SCFAs regulation.

Postmenopausal osteoporosis coexisting with sarcopenia: the role and mechanisms of estrogen.

Estrogens (estradiol, estriol, and estrone) are important hormones that directly and indirectly regulate the metabolism and function of bone and skeletal muscle via estrogen receptors. Menopause causes a dramatic reduction in the concentration of estrogen in the body. This contributes to a decline in bone and skeletal muscle function, thereby resulting in osteoporosis and sarcopenia. Menopausal women often experience osteoporosis and muscle wasting, and clinicians recognize estrogen as playing an important role in these conditions, particularly in women. Bone and muscle are closely related endocrine tissues that synthesize and produce various cytokines. These bone- and muscle-derived cytokines, including interleukin-6, irisin, ß-aminoisobutyric acid, osteocalcin, fibroblast growth factor-23, and sclerostin, regulate both local and distant tissues, and they mediate the crosstalk between bone and skeletal muscle. This review examines the metabolic effects of estrogen on bone and skeletal muscle and describes cytokine-mediated bone-muscle crosstalk in conditions of estrogen deficiency.

Bone Marrow Stromal Stem Cell Fate Decision: A Potential Mechanism For Bone Marrow Adipose Increase with Aging-related Osteoporosis.

OBJECTIVE: Osteoporosis is a systemic bone disease that seriously threatens the health and quality of life in middle-aged and older adults. In this review, we describe the relationship between bone marrow adipose tissue and aging osteoporosis and mainly focus on bone marrow mesenchymal stem cell osteogenic-adipose differentiation fate with aging along with the relevant mechanisms responsible for these changes. METHODS: We summarized recent advances in regulating the bone marrow mesenchymal stem cell differentiation due to aging in this review. RESULTS: Aging-related bone mass loss is accompanied by expanding bone marrow adipose because of an imbalance of bone marrow mesenchymal stem cell differentiation, resulting in adipogenesis. Ectopic adipocytes in the bone marrow increase with age and are a key factor responsible for the aging-related bone mass decrease. Transcription factors and classical regulating pathways are involved in this process during aging. CONCLUSION: As the global aging population increases, not only older women but also older men face a great fracture risk. Therefore, finding molecular mechanisms controlling the stimulating adipogenesis in BMSC during aging is important for providing the new cue for prevention and therapeutics for aging-related bone loss. Furthermore, upon physical examination of older people, except for the bone mineral density and bone turnover biochemical marker, the bone marrow adipose measurement should be taken into account when assessing the fracture risk and treatment plan that will be beneficial in clinical practice.

Brain network mechanism of acupuncture for chronic spontaneous urticaria: a functional magnetic resonance imaging study protocol.

Introduction: Chronic spontaneous urticaria (CSU) is a common skin condition that can significantly impact patients' quality of life. Although studies have demonstrated the efficacy of acupuncture in treating CSU, the underlying mechanisms remain unclear. Dysfunction within the brain's default mode network (DMN) represents a fundamental characteristic of central pathological changes associated with CSU. Therefore, it is hypothesized that improving brain network dysfunction could serve as a key mechanism through which acupuncture exerts its therapeutic effects. This study aims to provide evidence supporting this hypothesis. Methods and analysis: This study, a parallel, randomized, sham-controlled functional neuroimaging investigation will be conducted in China. We aim to enroll 50 patients with CSU and 25 healthy controls, distributing them evenly between the acupuncture and sham acupuncture groups in a 1:1 ratio. The total observation period will span 6 weeks, including 2 weeks designated for the baseline phase and 4 weeks allocated for the clinical treatment phase. Prior to treatment, all participants will undergo magnetic resonance scanning, clinical index detection, and microbiota collection. Following treatment, the patients with CSU will be retested for these indicators. Using resting-state functional connectivity (rsFC) analysis, dynamic Functional Connection (dFC) analysis, and brain microstate extraction technology combined with correlation analysis of microbiota and clinical indicators, the regulatory mechanism of acupuncture on the brain network of CSU will be evaluated from multiple dimensions. Ethics and dissemination: This trial was approved by the Biomedical Ethics Review Committee of the West China Hospital, Sichuan University (No. 2022-1255). Each participant will provide written informed consent to publish any potentially identifiable images or data.Clinical trial registrationhttps://www.chictr.org.cn/, identifier: ChiCTR2200064563.

Bone marrow adiposity during pathologic bone loss: molecular mechanisms underlying the cellular events.

Bone marrow (BM) is a heterogeneous niche where bone marrow stromal cells (BMSCs), osteoblasts, osteoclasts, adipocytes, hematopoietic cells, and immune cells coexist. The cellular composition of BM changes with various pathophysiological states. A reduction in osteoblast number and a concomitant increase in adipocyte number in aging and pathological conditions put bone marrow adipose tissue (BMAT) into spotlight. Accumulating evidence strongly supports that an overwhelming production of BMAT is a major contributor to bone loss disorders. Therefore, BMAT-targeted therapy can be an efficient and feasible intervention for osteoporosis. However, compared to blocking bone-destroying molecules produced by BMAT, suppressing BMAT formation is theoretically a more effective and fundamental approach in treating osteoporotic bone diseases. Thus, a deep insight into the molecular basis underlying increased BM adiposity during pathologic bone loss is critical to formulate strategies for therapeutically manipulating BMAT. In this review, we comprehensively summarize the molecular mechanisms involved in adipocyte differentiation of BMSCs as well as the interaction between bone marrow adipocytes and osteoclasts. More importantly, we further discuss the potential clinical implications of therapeutically targeting the upstream of BMAT formation in bone loss diseases.

Inpatient Quality-of-Care Measures for Heart Failure: Treatment Gaps and Opportunities in the Contemporary Era.

BACKGROUND: Quality of care measures are vital tools to assess processes of care within and between health care systems. The 2020 American College of Cardiology/AHA performance measures for heart failure provide a new set of such measures. We evaluated the achievement of these and other performance measures within the Veterans Affairs hospital system in a contemporary cohort of patients hospitalized for heart failure. METHODS: Hospital discharges from January 2010 to February 2021 with a primary diagnosis of heart failure (n=289 810) were evaluated. Adherence to each measure was determined using the measure's stated definition and by site. RESULTS: Among patients with reduced ejection fraction (53.0%), beta blocker use was high (89.0%), ACE (angiotensin-converting enzyme) inhibitor, angiotensin receptor blocker, or angiotensin receptor-neprilysin inhibitor (ARNI) use decreased over time (75.3% in 2010, 55.8% in 2020), and hydralazine/nitrate use in eligible Black patients (19.3%) was low. While 68.1% were eligible for ARNI, only 6.0% received them, reaching 17.2% by 2020. Mineralocorticoid receptor antagonists were used in 49.3% of those eligible; laboratory testing 7 days after their initiation was 73.0%, detecting hyperkalemia in 2.2%, although it occurred in 13.7% by 90 days. Achievement of ≥50% target dose was low (beta blocker 45.9%, ACE inhibitor/angiotensin receptor blocker 31.6%, ARNI 19.0%) and for ACE inhibitor/angiotensin receptor blocker/ARNI, decreased over time. Discharge appointments were 56.2% at 7 days and 78.8% at 14 days. Cardiac rehabilitation referral was low (10.5%) but increased. There were significant site-level differences, particularly for hydralazine, ARNI, devices, and cardiac rehabilitation. CONCLUSIONS: Important inpatient quality of care measures can be readily measured across the Veterans Administration health care system from electronic health records. Treatment gaps and site-level differences persisted into the contemporary era and will likely be exacerbated as newer treatments are added to this complex baseline. These measures and methods also offer the opportunity to target global, local, and individual processes of care for innovative quality improvement initiatives.

Transcutaneous electrical acupoint stimulation combined with electroacupuncture promotes rapid recovery after abdominal surgery: Study protocol for a randomized controlled trial.

Introduction: The most frequent complications after abdominal surgery include a decrease or loss of appetite, abdominal distension, abdominal pain caused by reduced gastrointestinal motility, anal arrest with intestinal distension and defecation, and nausea and vomiting due to anesthetic and opioid analgesic administration. These complications severely affect postoperative recovery, prolong hospital stay, and increase the financial burden. The objective of this study is to investigate the efficacy and safety of three acupoint stimulation modalities (electroacupuncture [EA], transcutaneous electrical acupoint stimulation [TEAS], and transcutaneous acupoint electrical stimulation combined with EA [TEAS+EA]), and two EA instrument waveforms (continuous wave and dilatational wave) for rapid recovery after abdominal surgery. Methods and analysis: A total of 560 patients will be recruited and randomly allocated to receive one of the following seven interventions: continuous wave EA, continuous wave TEAS, continuous wave TEAS + EA, dilatational wave EA, dilatational wave TEAS, dilatational wave TEAS + EA, and a control. For this study, continuous waves at 2 Hz, and dilatational waves at 2/50 Hz would be selected. The points to be stimulated by EA are the bilateral Neiguan (PC6), Hegu (LI6), Zusanli (ST36), Shangjuxu (ST37), and Xiajuxu (ST39), and TEAS would stimulate the bilateral Liangmen (ST21) and Daheng (SP15). The control group will neither receive EA nor TEAS. All patients will undergo an enhanced recovery plan after surgery and be provided with standardized perioperative management. Treatment will start on the first postoperative day and be administered once daily in the morning until the patient regains spontaneous bowel movements and can tolerate oral intake of solid food. The primary outcome is a composite of time to first defecation and time to tolerance of a solid diet. Secondary outcomes include time to first exhaustion; time of first defecation; time of tolerance of a solid diet; time to the first ambulation; length of hospital stay from surgery to discharge; visual analog scale score for postoperative daily pain, nausea, and vomiting; incidence of postoperative complications; and treatment acceptability. Discussion: This study will compare the efficacy and safety of three acupoint stimulation methods and two EA instrument waveforms for rapid recovery after abdominal surgery. Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2100043883.

Moxibustion as adjuvant therapy for preventing bone loss in postmenopausal women: protocol for a randomised controlled trial.

INTRODUCTION: Postmenopausal osteoporosis, caused by ageing and oestrogen deficiency, seriously threatens women's physical and mental health. Postmenopausal osteopenia is the transition from healthy bone to osteoporosis, and it may be the key period for preventing bone loss. Moxibustion, a physical therapy of Traditional Chinese Medicine, has potential benefits for osteoporosis treatment and prevention, but it has not been adequately studied. This study aims to explore the clinical effects and safety of moxibustion in delaying bone loss in postmenopausal women. METHODS AND ANALYSIS: In this parallel-design, randomised, patient-blind and assessor-blind, controlled clinical study, 150 women with osteopenia at low fracture risk will be randomly assigned to a moxibustion treatment (MT) group or a placebo-moxibustion control (PMC) group in a 1:1 ratio. In addition to the fundamental measures (vitamin D3 and calcium) as recommended by the guidelines, participants of the two groups will receive MT or PMC treatment for 42 sessions over 12 months. The primary outcome will be the bone mineral density (BMD) of the lumbar spine at the end of the 12-month treatment, and secondary outcomes will be the BMD of the femoral neck and total hip, T-scores, bone turnover markers, serum calcium levels, serum magnesium levels, serum phosphorus levels, serum parathyroid hormone levels and 25-hydroxyvitamin D levels, intensity of bone pain, quality of life, incidence of osteoporosis and fractures, usage of emergency drugs or surgery, participant self-evaluation of therapeutic effects and the rate of adverse events. All statistical analyses will be performed based on the intention-to-treat and per-protocol principle. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (permission number: 2021-1243). The results are expected to be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100053953.

Fc receptor-like 5 gene polymorphisms and mRNA expression are associated with liver fibrosis in chronic hepatitis B.

Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB). Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined. Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093-3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067-6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p < 0.001). The fibrosis patients carried TT or CT genotype of rs6692977 had significantly higher FCRL5 mRNA expression levels than those carried CC genotype (t = 2.859, p = 0.005). The mRNA expression levels of FCRL5, APRI, and FIB-4 index showed predictive efficacy in liver fibrosis with cut-off values of 0.75 (AUC = 0.896, 95% CI = 0.856-0.935), 0.45 (AUC = 0.852, 95% CI = 0.802-0.902) and 1.84 (AUC = 0.765, 95% CI = 0.703-0.826), respectively. Conclusion: FCRL5 gene rs6692977 polymorphisms and mRNA expression levels are associated with liver fibrosis in CHB patients.

Electroacupuncture at Acupoint ST36 (Zusanli) Improves Intestinal Motility Dysfunction Via Increasing the Proportion of Cholinergic Neurons in Rat Ileal Myenteric Ganglia after Severe Acute Pancreatitis.

Using a severe acute pancreatitis (SAP) rat model, the mechanism of electroacupuncture (EA) were studied on the intestinal function of pancreatitis. The SAP models were established by injecting 30% L-ornithine at hourly intervals, and were divided into two groups (14 in each): SAP model group, which was not treated, and EA group, which received EA at ST36 at a frequency of 1-2 Hz and amplitude of 1 mA for 30 min twice a day. Fourteen rats were also included as the control group. After EA, the intestinal propulsion was measured. In the distal ileum myenteric plexus, the density of HuC/D and the proportion of cholinergic neurons were measured using immunohistochemistry. Compared to the SAP model group, the EA group demonstrated significant improvements in intestinal propulsion rates. Furthermore, after EA, the density of myenteric neurons in the ileum returned to normal levels and the proportion of cholinergic neurons was increased compared to the SAP model group. And finally, EA alleviated the damage to the pancreas. Thus, our results suggest that EA stimulation at ST36 can partly restore the enteric neuron function and improve intestinal motility dysfunction, therefore could ameliorate SAP. The enteric nervous system can participate in changes in intestinal motility by affecting cholinergic neurons.