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ObjectiveDespite the fact that China amounts to one-fifth of the world’s population, has a higher proportion of the elderly, and has a higher prevalence of osteoporosis and fracture, limited studies have investigated the association between dietary patterns and bone mineral density (BMD) as well as fracture risk among the elderly Chinese population. We aimed to investigate the association between different dietary patterns and BMD as well as the risk of fractures, and this association may vary between elderly women and men.MethodsBuilding upon the China Osteoporosis Prevalence Study, we included 17,489 subjects aged ≥40 years old randomly sampled across 44 counties/districts of 11 provinces or municipalities in China who completed a food frequency questionnaire. BMD was measured by dual x-ray absorptiometry. Vertebral fracture was defined based on lateral spine radiographs using the semi-quantitative technique of Genant.ResultsA diet rich in “carnivorous”, “vegetarian”, “dairy, fruit, and egg” was significantly associated with higher BMD at total hip (TH), femoral neck (FN), and lumbar spine 1–4 (L1–4). Yet, a diet rich in “beverage and fried food” was associated with a lower BMD at the FN and L1–4. High quartiles of the carnivorous diet were associated with 34%–39% reduced risk of clinical fracture in the past 5 years and vertebral fracture. Stronger associations were observed among women. Sensitivity analysis among postmenopausal women presented even stronger positive associations between carnivorous and vegetarian diets and high BMD, as well as between carnivorous diet and reduced risk of fractures.ConclusionsOur study suggested that a diet rich in meat, vegetables, and dairy, fruit, and eggs might be associated with greater BMD and a lower fracture risk, while beverage and fried foods may be associated with a lower BMD at L1–4, especially among elderly women. These findings are relevant to provide recommendations on dietary nutrition regarding the elderly population at high risk of osteoporosis and fractures, especially postmenopausal women.

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery.

BackgroundElderly people are at high risk of falls due to decreased muscle strength. So far, there is currently no officially approved medication for treating muscle strength loss. The active vitamin D analogues are promising but inconsistent results have been reported in previous studies. The present study was to meta-analyze the effect of active vitamin D analogues on muscle strength and falls in elderly people.MethodsThe protocol was registered with PROSPERO (record number: CRD42021266978). We searched two databases including PubMed and Cochrane Library up until August 2023. Risk ratio (RR) and standardized mean difference (SMD) with 95% confidence intervals (95% CI) were used to assess the effects of active vitamin D analogues on muscle strength or falls.ResultsRegarding the effects of calcitriol (n= 1), alfacalcidol (n= 1) and eldecalcitol (n= 1) on falls, all included randomized controlled trials (RCT) recruited 771 participants. Regarding the effects of the effects of calcitriol (n= 4), alfacalcidol (n= 3) and eldecalcitol (n= 3) on muscle strength, all included RCTs recruited 2431 participants. The results showed that in the pooled analysis of three active vitamin D analogues, active vitamin D analogues reduced the risk of fall by 19%. Due to a lack of sufficient data, no separate subgroup analysis was conducted on the effect of each active vitamin D analogue on falls. In the pooled and separate analysis of active vitamin D analogues, no significant effects were found on global muscle, hand grip, and back extensor strength. However, a significant enhancement of quadriceps strength was observed in the pooled analysis and separate analysis of alfacalcidol and eldecalcitol. The separate subgroup analysis on the impact of calcitriol on the quadriceps strength was not performed due to the lack to sufficient data. The results of pooled and separate subgroup analysis of active vitamin D analogues with or without calcium supplementation showed that calcium supplementation did not affect the effect of vitamin D on muscle strength.ConclusionsThe use of active vitamin D analogues does not improve global muscle, hand grip, and back extensor strength but improves quadriceps strength and reduces risk of falls in elderly population.

Purpose: We aimed to investigate the status of serum 25-hydroxyvitamin D [25(OH)D] among Chinese postmenopausal women in a multicenter cross-sectional study.Methods: Non-institutionalized postmenopausal women aged ≥55 years were recruited from urban and rural areas in 7 geographically different regions in China. Subject enrollment was executed during the summer and the winter. Vitamin D insufficiency and deficiency were defined as 25(OH)D < 30 and< 20 ng/ml, and was measured by liquid chromatography-tandem mass spectrometry. Women were referred to a dual-energy x-ray absorptiometry (DXA) if they had a medium-to-high fracture risk suggested by Osteoporosis Self-Assessment Tool for Asians (OSTA).Results: Among all subjects, 91.2% (1,535/1,684, 95%CI: 89.7, 92.5) had vitamin D insufficiency and 61.3% had vitamin D deficiency (1,033/1,684, 95%CI: 59.0, 63.7). The prevalence of vitamin D deficiency was significantly higher in urban dwellers (64.9 vs. 57.7% in rural, P = 0.002) and in winter-enrolled subjects (84.7 vs. 41.3% in summer, P < 0.0001). The prevalence of vitamin D inadequacy did not increase in trend by latitude and was numerically lower in women who had high fracture risk and osteoporosis. A non-curvilinear change of intact parathyroid hormone (iPTH) levels was observed at 25(OH)D >16.78 ng/mL.Conclusions: The prevalence of vitamin D inadequacy was remarkable among Chinese postmenopausal women and independent of fracture risk assessed by OSTA or osteoporosis suggested by DXA. Winter season, urban residence, however not latitude, were significantly associated with a higher likelihood of vitamin D deficiency. Optimal vitamin D status for iPTH and bone-related outcomes merits further investigation in this population.

Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery. [ABSTRACT FROM AUTHOR]

Context: A germline mutation can be identified in up to 10% of patients with primary hyperparathyroidism (PHPT). In 2017, a high frequency of the GCM2 [(NM_ 004752.4) c.1181A> C; p.Tyr394Ser; rs142287570] variant was reported in PHPT Ashkenazi Jews (AJ). Objective: To evaluate the presence of the GCM2 p.Tyr394Ser variant in Israeli patients addressed for genetic evaluation to characterize their phenotype and clinical management. Method: Patients with PHPT who underwent addressed for genetic screening for suspected familial hypocalciuric hypercalcemia (FHH), a family history of isolated hyperparathyroidism (FIHP), or failed parathyroidectomy with persistent PHPT were recruited. Those with normal initial selected gene sequencing or hyperparathyroid genetic panel completed the GCM2 p.Tyr394Ser variant sequencing. The prevalence of this variant was evaluated using our local genomic database. Results: A total of 42 single individuals from unrelated kindreds were evaluated. A disease-causing mutation was found in 11 (26.1%) patients: 10 were diagnosed with FHH (eight CASR and two AP2S1 mutations), and one patient had a CKN2B mutation. In 28 of the remaining patients, the GCM2 p.Tyr394Ser variant was positive in three (10.7%), and all were AJ. Within AJ (15/28, 53.5%), the rate of the p.Tyr394Ser variant was 3/15 (20%), and of those, two had a history of familial isolated hyperparathyroidism. Multi-glandular parathyroid adenoma/hyperplasia was also observed in two of these patients. No clinical or laboratory findings could discriminate patients with the GCM2 p.Tyr394Ser variant from those with FHH. Cinacalcet normalized the calcium levels in one patient. The prevalence of the GCM2 p.Tyr394Ser variant in 15,407 tests in our local genomic database was 0.98%. Conclusion: In contrast to previous observations, the GCM2 p.Tyr394Ser variantassociated phenotype may be mild in AJ with FIHP, sometimes mimicking FHH. Because surgery may be curative, surgeons should be aware of the possibility of multiple gland diseases in these patients. The clinical spectrum and clinical utility of screening for this variant warrant further investigation. [ABSTRACT FROM AUTHOR]

Background: Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. Methods and analysis: We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D2 supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months postintervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D2 and 25(OH)D3 levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. Discussion: Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

We present the case of a 9-year-old girl who presented with symptomatic hypercalcemia from primary hyperparathyroidism (PHPT). Laboratory results revealed elevated serum calcium 12.1 mg/dl (ref: 9.1-10.4), elevated ionized calcium 6.8 (ref: 4.5-5.6) mg/dl, phosphorus 3.8 (ref: 3.3-5.1) mg/dl, 25-OH vitamin D 20.1 (30-100) ng/ml, and elevated intact PTH 70 (15-65) pg/ml, consistent with the diagnosis of PHPT. She had persistent hyperparathyroidism after bilateral neck exploration, left thyroid lobectomy, and transcervical thymectomy. Neither inferior gland was identified. No parathyroid tissue was seen on histology. Repeat preoperative imaging identified a 7-mm × 5-mm adenoma on 4DCT not seen on 99Tc-sestamibi parathyroid scan. The patient then underwent a successful redo parathyroidectomy with removal of a submucosal left parathyroid adenoma at the superior aspect of the thyroid cartilage in the piriform sinus. Her biochemical work-up remains consistent with surgical cure 6 months after surgery. Herein, we also review common locations for ectopic parathyroid adenomas. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the association between nerve conduction velocity (NCV) and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). Methods: This study retrospectively collected medical data of T2DM patients who underwent dual-energy X-ray absorptiometry and nerve conduction study at the Shanghai Ruijin Hospital, Shanghai, China. The primary outcome was the total hip BMD T-score. The main independent variables were motor nerve conduction velocities (MCVs), sensory nerve conduction velocities (SCVs), and composite Z-scores of MCV and SCV. T2DM patients were divided into total hip BMD T-scores < -1 and total hip BMD T-scores ≥ -1 groups. The association between the primary outcome and main independent variables was evaluated by Pearson bivariate correlation and multivariate linear regression. Results: 195 female and 415 male patients with T2DM were identified. In male patients with T2DM, bilateral ulnar, median, and tibial MCVs and bilateral sural SCVs were lower in the total hip BMD T-score < -1 group than T-score ≥ -1 group (P < 0.05). Bilateral ulnar, median, and tibial MCVs, and bilateral sural SCVs showed positive correlations with total hip BMD T-score in male patients with T2DM (P < 0.05). Bilateral ulnar and tibial MCVs, bilateral sural SCVs, and composite MCV SCV and MSCV Z-scores were independently and positively associated with total hip BMD T-score in male patients with T2DM, respectively (P < 0.05). NCV did not show significant correlation with the total hip BMD Tscore in female patients with T2DM. Conclusion: NCV showed positive association with total hip BMD in male patients with T2DM. A decline in NCV indicates an elevated risk of low BMD (osteopenia/osteoporosis) in male patients with T2DM. [ABSTRACT FROM AUTHOR]

Objective: To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR). Methods: Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inversevariance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR-Egger methods. The pleiotropy of MR results was determined using MR-Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results. Results: Based on IVW, MR-Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (Pbeta > 0.05 in all models). IVW and MR-Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (Pbeta> 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (Pbeta> 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (Pbeta>0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR. Conclusion: Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded. [ABSTRACT FROM AUTHOR]

Neutrophils are the most abundant type of white blood cell in most mammals including humans. The primary role of these cells is host defense against microbes and clearance of tissue debris in order to facilitate wound healing and tissue regeneration. The recruitment of neutrophils from blood into tissues is a key step in this process and is mediated by numerous different chemoattractants. The neutrophil migratory response is essential for host defense and survival, but excessive tissue accumulation of neutrophils is observed in many inflammatory disorders and strongly correlates with disease pathology. The vitamin D binding protein (DBP) is a circulating multifunctional plasma protein that can significantly enhance the chemotactic activity of neutrophil chemoattractants both in vitro and in vivo. Recent in vivo studies using DBP deficient mice showed that DBP plays a larger and more central role during inflammation since it induces selective recruitment of neutrophils, and this cofactor function is not restricted to C5a, as prior in vitro studies indicated, but can enhance chemotaxis to many chemoattractants. DBP also is an extracellular scavenger for actin released from damaged/dead cells and formation of DBP-actin complexes is an immediate host response to tissue injury. Recent in vitro evidence indicates that DBP bound to G-actin, and not free DBP, functions as an indirect but essential cofactor for neutrophil migration. DBP-actin complexes always will be formed regardless of what initiated an inflammation, since release of actin from damaged cells is a common feature in all types of injury and DBP is abundant and ubiquitous in all extracellular fluids. Indeed, these complexes have been detected in blood and tissue fluids from both humans and experimental animals following various forms of injury. The published data strongly supports the premise that DBP-actin complexes are the functional neutrophil chemotactic cofactor that enhances neutrophil chemotaxis in vitro and augments neutrophilic inflammation in vivo. This review will assess the fundamental role of DBP in neutrophilic inflammation and injury. [ABSTRACT FROM AUTHOR]

Keywords: vitamin D binding protein; total 25-hydroxyvitamin D; free 25-hydroxyvitamin D; 1,25-dihydroxyvitamin D; bioavailable 25-hydroxyvitamin D Vitamin D binding protein (DBP) is a major plasma carrier for vitamin D and its metabolites. DBP has a single binding site for all vitamin D metabolites with a high affinity for 25(OH)D, thereby creating a large pool of circulating 25(OH)D, which prevents rapid vitamin D deficiency. [Extracted from the article]