Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer.

BACKGROUND: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. METHODS: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. RESULTS: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. CONCLUSION: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.

Multimorbidity clusters potentially superior to individual diseases for stratifying fracture risk in older people: a nationwide cohort study.

RATIONALE: Comorbidities are common in fracture patients, but the interaction between fracture and comorbidities remains unclear. This study aimed to define specific multimorbidity clusters in older adults and quantify the association between the multimorbidity clusters and fracture risk. METHODS: This nationwide cohort study includes 1.7 million adults in Denmark aged ≥50 years who were followed from 2001 through 2014 for an incident low-trauma fracture. Chronic diseases and fractures were identified from the Danish National Hospital Discharge Register. Latent class analysis and Cox's regression were conducted to define the clusters and quantify fracture risk, respectively. RESULTS: The study included 793 815 men (age: 64 ± 10) and 873 524 women (65.5 ± 11), with a third having ≥1 chronic disease. The pre-existent chronic diseases grouped individuals into low-multimorbidity (80.3% in men, 83.6% in women), cardiovascular (12.5%, 10.6%), malignant (4.1%, 3.8%), diabetic (2.4%, 2.0%) and hepatic clusters (0.7%, men only). These clusters distinguished individuals with advanced, complex, or late-stage disease from those having earlier-stage disease. During a median follow-up of 14 years (IQR: 6.5, 14), 95 372 men and 212 498 women sustained an incident fracture. The presence of multimorbidity was associated with a significantly greater risk of fracture, independent of age and sex. Importantly, the multimorbidity clusters had the highest discriminative performance in assessing fracture risk, whereas the strength of their association with fracture risk equalled or exceeded that of both the individual chronic diseases most prevalent in each cluster and of counts-based comorbidity indices. CONCLUSIONS: Future fracture prevention strategies should take comorbidities into account. Multimorbidity clusters may provide greater insight into fracture risk than individual diseases or counts-based comorbidity indices.

Reciprocal negative feedback regulation of ATF6α and PTEN promotes prostate cancer progression.

Phosphatase and tensin homolog (PTEN) loss tightly correlates with prostate cancer (PCa) progression and metastasis. Inactivation of PTEN leads to abnormal activation of PI3K/AKT pathway. However, results from clinical trials with AKT inhibitors in PCa have been largely disappointing. Identification of novel regulators of PTEN in PTEN-dysfunctional PCa is urgently needed. Here we demonstrated that the expression level of PTEN is inversely correlated with the signature score of unfolded protein response (UPR) in PCa. Importantly, PTEN suppresses the activity of ATF6α, via interacting to de-phosphorylate ATF6α and consequently inhibiting its nuclear translocation. Conversely, ATF6α promotes the ubiquitination and degradation of PTEN by inducing CHIP expression. Thus, ATF6α and PTEN forms a negative feedback loop during PCa progression. Combination of ATF6α inhibitor with AKT inhibitor suppresses tumor cell proliferation and xenograft growth. Importantly, this study highlighted ATF6α as a therapeutic vulnerability in PTEN dysfunctional PCa.

Follow-up Bone Mineral Density Testing: 2023 Official Positions of the International Society for Clinical Densitometry.

Dual-energy X-ray absorptiometry (DXA) is the gold standard method for measuring bone mineral density (BMD) which is most strongly associated with fracture risk. BMD is therefore the basis for the World Health Organization's densitometric definition of osteoporosis. The International Society for Clinical Densitometry (ISCD) promotes best densitometry practices and its official positions reflect critical review of current evidence by domain experts. This document reports new official positions regarding follow-up DXA examinations based on a systematic review of literature published through December 2022. Adoption of official positions requires consensus agreement from an expert panel following a modified RAND protocol. Unless explicitly altered by the new position statements, prior ISCD official positions remain in force. This update reflects increased consideration of the clinical context prompting repeat examination. Follow-up DXA should be performed with pre-defined objectives when the results would have an impact on patient management. Testing intervals should be individualized according to the patient's age, sex, fracture risk and treatment history. Incident fractures and therapeutic approach are key considerations. Appropriately ordered and interpreted follow-up DXA examinations support diagnostic and therapeutic decision making, thereby contributing to excellent clinical care. Future research should address the complementary roles of clinical findings, imaging and laboratory testing to guide management.

Is it harmful to me or to us? A dyadic analysis of Chinese young adults' dysfunctional individuation and romantic relationship satisfaction.

This study aimed at examining how romantically involved Chinese young adults' dysfunctional individuation was associated with their and their partners' perceptions of romantic relationship satisfaction. We recruited 296 Chinese couples who were currently in heterosexual romantic relationships at the university. The couples completed self-report measures of their dysfunctional individuation and relationship satisfaction. Results from the cross-sectional actor-partner interdependence model (APIM) indicated that (a) for both genders, actor effects existed: Chinese young adults' dysfunctional individuation was negatively associated with their romantic relationship satisfaction; (b) in terms of partners' effects, women's dysfunctional individuation was negatively associated with men's perceptions of relationship satisfaction; but (c) men's dysfunctional individuation was not significantly associated with women's perceptions of relationship satisfaction. The findings were the first to reveal the actor and partner effects of dysfunctional individuation on romantic relationship satisfaction. The study results provided practical implications regarding how young adults can have satisfying romantic relationships.

The association between multimorbidity and osteoporosis investigation and treatment in high-risk fracture patients in Australia: A prospective cohort study.

BACKGROUND: Multimorbidity is common among fracture patients. However, its association with osteoporosis investigation and treatment to prevent future fractures is unclear. This limited knowledge impedes optimal patient care. This study investigated the association between multimorbidity and osteoporosis investigation and treatment in persons at high risk following an osteoporotic fracture. METHODS AND FINDINGS: The Sax Institute's 45 and Up Study is a prospective population-based cohort of 267,153 people in New South Wales, Australia, recruited between 2005 and 2009. This analysis followed up participants until 2017 for a median of 6 years (IQR: 4 to 8). Questionnaire data were linked to hospital admissions (Admitted Patients Data Collection (APDC)), emergency presentations (Emergency Department Data Collection (EDDC)), Pharmaceutical Benefits Scheme (PBS), and Medicare Benefits Schedule (MBS). Data were linked by the Centre for Health Record Linkage and stored in a secured computing environment. Fractures were identified from APDC and EDDC, Charlson Comorbidity Index (CCI) from APDC, Dual-energy X-ray absorptiometry (DXA) investigation from MBS, and osteoporosis treatment from PBS. Out of 25,280 persons with index fracture, 10,540 were classified as high-risk based on 10-year Garvan Fracture Risk (age, sex, weight, prior fracture and falls) threshold ≥20%. The association of CCI with likelihood of investigation and treatment initiation was determined by logistic regression adjusted for education, socioeconomic and lifestyle factors). The high-risk females and males averaged 77 ± 10 and 86 ± 5 years, respectively; >40% had a CCI ≥2. Only 17% of females and 7% of males received a DXA referral, and 22% of females and 14% males received osteoporosis medication following fracture. A higher CCI was associated with a lower probability of being investigated [adjusted OR, females: 0.73 (95% CI, 0.61 to 0.87) and 0.43 (95% CI, 0.30 to 0.62); males: 0.47 (95% CI, 0.33 to 0.68) and 0.52 (0.31 to 0.85) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively] and of receiving osteoporosis medication [adjusted OR, females: 0.85 (95% CI, 0.74 to 0.98) and 0.78 (95% CI, 0.61 to 0.99); males: 0.75 (95% CI, 0.59 to 0.94) and 0.37 (95% CI, 0.23 to 0.53) for CCI: 2 to 3, and ≥4 versus 0 to 1, respectively]. The cohort is relatively healthy; therefore, the impact of multimorbidity on osteoporosis management may have been underestimated. CONCLUSIONS: Multimorbidity contributed significantly to osteoporosis treatment gap. This suggests that fracture risk is either underestimated or underprioritized in the context of multimorbidity and highlights the need for extra vigilance and improved fracture care in this setting.

Hepatic ELOVL3 is dispensable for lipid metabolism in mice.

Very long-chain fatty acid elongase 3 (ELOVL3) catalyzes the synthesis of C20-C24 fatty acids and is highly expressed in the liver and adipose tissues. The deficiency of Elovl3 exhibits an anti-obesity effect in mice, but the specific role of hepatic ELOVL3 in lipid metabolism remains unclear. Here we demonstrate that hepatic Elovl3 is not required for lipid homeostasis or the pathogenesis of diet-induced obesity and hepatic steatosis. We generated Elovl3 liver-specific knockout mice via Cre/LoxP approach, which maintained normal expression of ELOVL1 or ELOVL7 in the liver. Unexpectedly, the mutant mice did not show significant abnormalities in body weight, liver mass and morphology, liver triglyceride content, or glucose tolerance when fed normal chow or even a low-fat diet. Moreover, deletion of hepatic Elovl3 did not significantly affect body weight gain or hepatic steatosis induced by high-fat diet. Lipidomic analysis revealed that the lipid profiles were not significantly altered by the loss of hepatic Elovl3. Unlike its global knockouts, the mice lacking Elovl3 specifically in liver displayed normal expression of genes involved in hepatic de novo lipogenesis, lipid uptake, or beta-oxidation at the mRNA and protein levels. Collectively, our data indicate that hepatic ELOVL3 is dispensable for metabolic homeostasis or diet-induced metabolic disease.

The co-regulation of the gut microbiome and host genes might play essential roles in metformin gastrointestinal intolerance.

Metformin is commonly used, but approximately 20% of patients experience gastrointestinal intolerance, leading to medication discontinuation for unclear reasons and a lack of effective management strategies. In this study, the 18 fecal and blood samples were analyzed using 16S rRNA and mRNA transcriptome, respectively. These samples included 3 fecal and 4 blood from metformin-tolerant T2D patients before and after metformin treatment (T and Ta), 3 fecal and 5 blood from metformin-intolerant T2D patients before and after treatment (TS and TSa), and 6 fecal samples from healthy controls. The results showed that certain anti-inflammatory gut bacteria and gene, such as Barnesiella (p = 0.046), Parabacteroides goldsteinii (p = 0.016), and the gene JUND (p = 0.0002), exhibited higher levels in metformin-intolerant patients, and which decreased after metformin treatment (p < 0.05). This potentially invalidates patients' anti-inflammatory effect and intestinal mucus barrier protection, which may lead to alterations in intestinal permeability, decreased gut barrier function, and gastrointestinal symptoms, including diarrhea, bloating, and nausea. After metformin treatment, primary bile acids (PBAs) production species: Weissella confusa, Weissella paramesenteroides, Lactobacillus brevis, and Lactobacillus plantarum increased (p < 0.05). The species converting PBAs to secondary bile acids (SBAs): Parabacteroides distasonis decreased (p < 0.05). This might result in accumulation of PBAs, which also may lead to anti-inflammatory gene JUND and SQSTM1 downregulated. In conclusion, this study suggests that metformin intolerance may be attributed to a decrease in anti-inflammatory-related flora and genes, and also alterations in PBAs accumulation-related flora. These findings open up possibilities for future research targeting gut flora and host genes to prevent metformin intolerance.

Reduced Proteolipid Protein 2 promotes endoplasmic reticulum stress-related apoptosis and increases drug sensitivity in acute myeloid leukemia.

BACKGROUND: The Proteolipid Protein 2 (PLP2), a protein in the Endoplasmic Reticulum (ER) membrane, has been reported to be highly expressed in various tumors. Previous studies have demonstrated that the reduced PLP2 can induce apoptosis and autophagy through ER stress-related pathways, leading to a decreased proliferation and aggressiveness. However, there is no research literature on the role of PLP2 in Acute Myeloid Leukemia (AML). METHODS: PLP2 expression, clinical data, genetic mutations, and karyotype changes from GEO, TCGA, and timer2.0 databases were analyzed through the R packages. The possible functions and pathways of cells were explored through GO, KEGG, and GSEA enrichment analysis using the clusterProfiler R package. Immuno-infiltration analysis was conducted using the Cibersort algorithm and the Xcell R package. RT-PCR and western blot techniques were employed to identify the PLP2 expression, examine the knockdown effects in THP-1 cells, and assess the expression of genes associated with endoplasmic reticulum stress and apoptosis. Flow cytometry was utilized to determine the apoptosis and survival rates of different groups. RESULTS: PLP2 expression was observed in different subsets of AML and other cancers. Enrichment analyses revealed that PLP2 was involved in various tumor-related biological processes, primarily apoptosis and lysosomal functions. Additionally, PLP2 expression showed a strong association with immune cell infiltration, particularly monocytes. In vitro, the knockdown of PLP2 enhanced endoplasmic reticulum stress-related apoptosis and increased drug sensitivity in THP-1 cells. CONCLUSIONS: PLP2 could be a novel therapeutic target in AML, in addition, PLP2 is a potential endoplasmic reticulum stress regulatory gene in AML.

Hierarchical V4C3TX@NiO-reduced graphene oxide heterostructure hydrogels and defective reduced graphene oxide hydrogels as free-standing anodes and cathodes for high-performance asymmetric supercapacitors.

Asymmetric supercapacitors (ASCs) based on a battery-type anode and a capacitive-type cathode have been attracting extensive interest because of their high energy density. Herein, NiO nanosheets are hydrothermally deposited onto a V4C3TX substrate, which are then assembled into a 3D porous heterostructure hydrogel through a graphene oxide-assisted self-convergence hydrothermal process at low temperatures. The resultant hierarchical V4C3TX@NiO-RGO heterostructure hydrogel exhibits an ultrahigh specific capacitance of up to 1014.5 F g-1 at 1 A g-1. In addition, a defective reduced graphene oxide (DRGO) hydrogel is prepared using a cost-effective hydrothermal procedure followed by cobalt-catalyzed gasification, which shows a higher specific capacitance (258 F g-1 at 1 A g-1) than the untreated RGO hydrogel (176 F g-1). These two electrodes are then assembled into an ASC; the device features a stable operating voltage of 1.8 V, a maximum energy density of 86.22 W h kg-1 at 900 W kg-1, and excellent cycling stability at 96.4% capacitance retention after 10 000 cycles at 10 A g-1. The results from this work highlight the unique potential of MXene-based materials for the construction of high-performance ASCs.

Outcomes of different zero-profile spacers in the treatment of two-level cervical degenerative disk disease.

PURPOSE: The purpose of this study was to analyze the clinical and radiological outcomes of two different zero-profile spacers (ROI-C and anchor-C) in contiguous two-level ACDF for CDDD patients. METHODS: We retrospectively analyzed patients who underwent contiguous two-level ACDF due to CDDD between January 2015 and December 2020 in our hospital. Patients who received ROI-C and anchor-C were included as the study groups, and those who underwent plate-cage construct (PCC) were included as the control group. The primary outcome measures were radiographical parameters, and the secondary outcome measures were dysphagia, JOA scores and VAS scores for these patients. RESULTS: A total of 91 patients were enrolled in the study; there were 31, 21 and 39 patients in the ROI-C, anchor-C and PCC groups, respectively. The mean follow-up duration was 24.52 months (range, 18-48 months) in the ROI-C group, 24.38 months (range, 16-52 months) in the anchor-C group and 25.18 months (range, 15-54 months) in the PCC group. The loss of the intervertebral space height and cage subsidence rate in the ROI-C group were significantly higher than those in the anchor-C group and PCC group at the final follow-up (P < 0.05). The ROI-C group showed a lower incidence of adjacent segment degeneration than the anchor-C group and PCC group, but the difference was not significant. The fusion rates were not different among these three groups. The early dysphagia rate was significantly lower in the patients with zero-profile spacers than in the PCC group (P < 0.05), but the difference was not significant at the last follow-up. No relevant differences were found in the JOA scores and VAS scores. CONCLUSIONS: Zero-profile spacers showed promising clinical outcomes in CDDD patients having contiguous two-level ACDF. However, ROI-C resulted in a higher intervertebral space height loss and a higher cage subsidence rate than anchor-C during the follow-up.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Changes in sucrose metabolism patterns affect the early maturation of Cassava sexual tetraploid roots.

BACKGROUND: Cassava (Manihot esculenta Crantz) is an important multiuse crop grown for economic and energy purposes. Its vegetative organs are storage roots, in which the main storage material is starch. The accumulation characteristics of starch in cassava roots can directly affect the yield, starch content and maturation of cassava storage roots. In this study, we used a cassava sexual tetraploid (ST), which showed early maturation heterosis in previous work, as the main test material. We analyzed the sucrose metabolism and starch accumulation characteristics of the ST and its parents from the leaf "source" to the storage root "sink" during different developmental stages and explored the regulatory mechanisms of ST storage root early maturation by combining the transcriptome data of the storage roots during the expansion period. RESULTS: The results showed that the trends in sucrose, glucose and fructose contents in the ST leaves were similar to those of the two parents during different stages of development, but the trends in the ST storage roots were significantly different from those of their parents, which showed high sucrose utilization rates during the early stage of development and decreased utilization capacity in the late developmental stage. Transcriptome data showed that the genes that were expressed differentially between ST and its parents were mainly involved in the degradation and utilization of sucrose in the storage roots, and four key enzyme genes were significantly upregulated (Invertase MeNINV8/MeVINV3, Sucrose synthase MeSuSy2, Hexokinase MeHXK2), while the expressions of key enzyme genes involved in starch synthesis were not significantly different. CONCLUSIONS: The results revealed that the pattern of sucrose degradation and utilization in the cassava ST was different from that of its parents and promoted early maturation in its tuberous roots. Starch accumulation in the ST from sucrose mainly occurred during the early expansion stage of the storage roots, and the starch content during this period was higher than that of both parents, mainly due to the regulation of invertase and hexokinase activities during sucrose metabolism. This study provides a basis for further genetic improvements to cassava traits and for breeding varieties that mature early and are adapted well to provide starch supply requirements.

Identification and functional characterization of three iridoid synthases in Gardenia jasminoides.

MAIN CONCLUSION: The discovery of three iridoid synthases (GjISY, GjISY2 and GjISY4) from Gardenia jasminoides and their functional characterization increase the understanding of iridoid scaffold/iridoid glycoside biosynthesis in iridoid-producing plants. Iridoids are a class of noncanonical monoterpenes that are found naturally in the plant kingdom mostly as glycosides. Over 40 iridoid glycosides (e.g., geniposide, gardenoside and shanzhiside) have been isolated from Gardenia jasminoides. They have multiple pharmacological properties and health-promoting effects. However, their biosynthetic pathway is poorly understood, and the iridoid synthase (ISY) responsible for the cyclization of the core scaffold remains unclear. In this study, three homologs of ISYs from G. jasminoides (GjISY, GjISY2 and GjISY4) were identified on the basis of transcriptomic data and functionally characterized. The genomic structure and intron-exon arrangement revealed that all three ISYs contained an intron. Biochemical assays indicated that all three recombinant enzymes reduced 8-oxogeranial to nepetalactol and its open forms (iridodials) as the products of the classical CrISY (Catharanthus roseus). In addition, all three enzymes reduced progesterone to 5-ß-prognane-3,20-dione. However, only GjISY2 and GjISY4 reduced 2-cyclohexen-1-one to cyclohexanone. Overall, the GjISY2 expression levels in the flowers and fruits were similar to the GjISY and GjISY4 expression levels. By contrast, the GjISY2 expression levels in the upper and lower leaves were substantially higher than the GjISY and GjISY4 expression levels. Among the three, GjISY2 exhibited the highest catalytic efficiency for 8-oxogeranial. GjISY2 might be the major contributor to iridoid biosynthesis in G. jasminoides. Collectively, our results advance the understanding of iridoid scaffold/iridoid glycoside biosynthesis in G. jasminoides and provide a potential target for metabolic engineering and breeding.

Spectroscopic coherent Raman imaging of Caenorhabditis elegans reveals lipid particle diversity.

Caenorhabditis elegans serves as a model for understanding adiposity and its connections to aging. Current methodologies do not distinguish between fats serving the energy needs of the parent, akin to mammalian adiposity, from those that are distributed to the progeny, making it difficult to accurately interpret the physiological implications of fat content changes induced by external perturbations. Using spectroscopic coherent Raman imaging, we determine the protein content, chemical profiles and dynamics of lipid particles in live animals. We find fat particles in the adult intestine to be diverse, with most destined for the developing progeny. In contrast, the skin-like epidermis contains fats that are the least heterogeneous, the least dynamic and have high triglyceride content. These attributes are most consistent with stored somatic energy reservoirs. These results challenge the prevailing practice of assessing C. elegans adiposity by measurements that are dominated by the intestinal fat content.

Dual Hip DXA. Is it Time to Change Standard Protocol?

Previous studies have examined the utility of bilateral DXA hip bone mineral density (BMD) scans. While most studies demonstrate an advantage of bilateral hip scanning, the studies have been limited by size, or have not included simultaneous lumbar spine scans. To analyse the utility of dual hip scans in a clinical environment, a large retrospective study was performed of DXA BMD of both hips, and lumbar spine, in 17,169 individuals assessed at one centre over 10 years. There was no clinically significant difference in the population mean femoral neck BMD of the left vs the right leg (0.878 vs 0.881g/cm2) or total proximal femoral BMD of the left vs the right leg (0.920 vs 0.919g/cm2). There were however discrepancies in individuals between hip t-scores. For the total hip 1,977 (11.5 %) and 147 (0.9 %) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. For the femoral neck 3,320 (19.3%) and 337 (2.0%) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. Of the total 17,169 individuals there were 2,776 subjects with osteoporosis (T≤ -2.5) using the lumbar spine and right hip, compared to 2,834 subjects using the lumbar spine and left hip. Using the lumbar spine and both hips identified 3,214 individuals with osteoporosis. Diagnosis based on use of the lumbar spine and right hip BMD, or lumbar spine and left hip BMD, therefore failed to identify 15.8%, or 13.4%, of osteoporotic subjects respectively. Additional scanning time required was assessed in 40 subjects prospectively. Performing lumbar spine and both hips, compared to lumbar spine and one hip, required an average additional scan time of 55 seconds. The recommendation of best practise for DXA BMD measurements should be reviewed to consider lumbar spine and dual hip DXA as standard of care.

Ultrasonography in the diagnosis of rotator cuff avulsion fracture.

Deepening the understanding of morphology and corresponding sonographic features of the greater tuberosity and the various fracture lines in avulsion fracture like the "horizontal line sign" and "double-line sign" and sharp bony prominence besides the defect on the greater tuberosity, can make it simple to identify avulsion fracture accurately and quickly.

Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss.

OBJECTIVES: Little is known about the long-term skeletal impact of bariatric procedures, particularly the increasingly commonly performed gastric sleeve surgery (GS). We examined bone density (BMD) change following three types of bariatric surgery Roux-en-Y gastric bypass (RYGB), GS and laparoscopic adjustable gastric banding (LAGB), compared with diet, over 36 months. METHODS: Non-randomized, prospective study of participants with severe obesity (n = 52), undergoing weight-loss interventions: RYGB (n = 7), GS (n = 21), LAGB (n = 11) and diet (n = 13). Measurements of calciotropic indices, gut hormones (fasting and post prandial) peptide YY (PYY), glucagon-like peptide 1 (GLP1) and adiponectin together with dual-X-ray absorptiometry and quantitative computed tomography scans were performed thorough the study. RESULTS: All groups lost weight during the first 12 months. Despite weight stability from 12 to 36 months and supplementation of calcium and vitamin D, there was progressive bone loss at the total hip (TH) over 36 months in RYGB -14% (95% CI: -12, -17) and GS -9% (95% CI: -7, -10). In RYGB forearm BMD also declined over 36 months -9% (95% CI: -6, -12) and LS BMD declined over the first 12 months -7% (95% CI: -3, -12). RYGB and GS groups experienced significantly greater bone loss until 36 months than LAGB and diet groups, which experienced no significant BMD loss. These bone losses remained significant after adjustment for weight loss and age. RYGB and GS procedures resulted in elevated postprandial PYY, adiponectin and bone turnover markers up to 36 months without such changes among LAGB and diet participants. CONCLUSIONS: RYGB and GS but not LAGB resulted in ongoing TH bone loss for three postoperative years. For RYGB, bone loss was also observed at LS and non-weight-bearing forearms. These BMD changes were independent of weight and age differences. We, therefore, recommend close monitoring of bone health following RYGB and GS surgeries.

The effect of square dance on family cohesion and subjective well-being of middle-aged and empty-nest women in China.

Researchers in this study aimed to examine the effect of square dance on the subjective well-being of middle-aged and empty-nest women, as well as the potential moderating role of group belongingness in the relationship between family cohesion and subjective well-being. A total of 331 middle-aged and empty-nest Chinese women participated in a survey to measure their family adaptability and cohesion, group belongingness, general well-being, and square-dancing participation information. The results were found as follows: (a) Chinese middle-aged and empty-nest women's family cohesion was positively associated with subjective well-being, and their group belongingness in square dance was positively associated with subjective well-being; (b) participation in square dance can be the moderator the relationship between family cohesion and subjective well-being; (c) group belongingness was found to be a moderator in the relationship between family cohesion and subjective well-being.

Total ginsenosides promote the IEC-6 cell proliferation via affecting the regulatory mechanism mediated by polyamines.

Epithelial cell proliferation has been demonstrated to be a critical modality for mucosal repair after gastrointestinal mucosal injury. This research aimed to investigate the effect of total ginsenosides upon the proliferation of intestinal epithelial cells (IEC-6), and elucidate its potential mechanisms through polyamine-regulated pathway including the expression of proliferation-related proteins. Total ginsenosides (PGE3) were extracted from Panax ginseng, a Chinese herbal medicine, whose chromatogram was obtained by high performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD). The cell proliferation, cell cycle distribution and the level of c-Myc, RhoA, Cdk2 proteins were detected to determine the effects of PGE3 at 25, 50 and100 mg/l doses on IEC-6. Furthermore, rats model of intestinal mucosal injury were induced by the subcutaneous injection of indomethacin, and the effect of Panax ginseng aqueous extracts (PGE1) on intestinal mucosal injury was observed. PGE3 could promote IEC-6 cell proliferation, reduce the proportion of G0/G1 phase cells and elevate the proportion of G2/M + S phase cells, and revert the proliferation and cell cycle arrest induced by DFMO (DL-a-difluoromethylornithine, an inhibitor of polyamines synthesis). PGE3 exposure enhanced the level of c-Myc, RhoA and Cdk2 proteins, and reversed the inhibition of these proteins expression induced by DFMO. The results of gross and pathological scores showed administration of PGE1 significantly alleviated intestinal mucosal injury of rats. Our findings indicate that total ginsenosides promoted the IEC-6 proliferation presumably via its regulation on cell cycle and the expression of proliferation-related proteins regulated by polyamines, and provided a novel perspective for exploring the repair effect of Panax ginseng upon gastrointestinal mucosal injury.