The Healing and therapeutic effects of perioperative bisphosphonate use in patients with fragility fractures: meta-analysis of 19 clinical trials.

OBJECTIVES: Previous evidence suggests that bisphosphonates (BPs) may lower the risk of recurrent fractures and enhance functional recovery in patients with fractures. However, there has been controversy regarding the optimal timing of treatment initiation for patients with fragility fractures. We conducted a meta-analysis to evaluate the available evidence on the use of BPs during the perioperative period and compared it to both non-perioperative periods and non-usage. METHODS: Electronic searches were performed using PubMed, EMBASE, Web of Science and the Cochrane Library published before February 2023, without any language restrictions. The primary outcomes included fracture healing rate, healing time, and new fractures. We also examined a wide range of secondary outcomes. Random effects meta-analysis was used. RESULTS: A total of 19 clinical trials involving 2543 patients were included in this meta-analysis. When comparing patients with non-perioperative BPs use in 4-6 weeks and approximately 10-12 weeks post-surgically, the overall risk ratios (RRs) of perioperative BPs use for healing rate were 1.06 (95% CI: 0.81, 1.38, p=0.69) and 1.02 (95% CI: 0.94, 1.11, p=0.65), respectively, suggesting no difference in healing rate between perioperative and non-perioperative BP initiation. For healing time, the overall mean difference between perioperative and non-perioperative periods was -0.19 week (95% CI: -1.03, 0.64, p=0.65) at approximately 10-12 weeks, indicating no significant impact of perioperative BP initiation on healing time. In terms of new fractures, the overall RR with BP use was 0.35 (95% CI: 0.17-0.73, p=0.005), when compared to patients without BPs use. This suggests a protective impact of BP use against new fractures compared to patients without BP use. Perioperative BP use was associated with a markedly higher likelihood of having adverse experiences, including fever (RR: 23.78, 95% CI: 8.29, 68.21, p< 0.001), arthralgia (RR: 10.20, 95% CI: 2.41, 43.16, p=0.002), and myalgia (RR: 9.42, 95% CI: 2.54, 34.87, p< 0.001), compared with non-BPs use. CONCLUSIONS: Treatment with BP during the perioperative period does not affect the healing process and has positive effects on therapy for patients with fragility fractures. These compelling findings underscore the potential efficacy of BP use during the perioperative period as a viable treatment option for patients with fragility fractures.

Observational and genetic association of non-alcoholic fatty liver disease and calcific aortic valve disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a predominant driver of chronic liver disease globally and is associated with increased cardiovascular disease morbidity and mortality. However, the association between NAFLD and calcific aortic valve disease remains unclear. We aimed to prospectively investigate the association between NAFLD and incident aortic valve calcification (AVC), as well as its genetic relationship with incident calcific aortic valve stenosis (CAVS). Methods: A post hoc analysis was conducted on 4226 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) database. We employed the adjusted Cox models to assess the observational association between NAFLD and incident AVC. Additionally, we conducted two-sample Mendelian randomization (MR) analyses to investigate the genetic association between genetically predicted NAFLD and calcific aortic valve stenosis (CAVS), a severe form of CAVD. We repeated the MR analyses by excluding NAFLD susceptibility genes linked to impaired very low-density lipoprotein (VLDL) secretion. Results: After adjustment for potential risk factors, participants with NAFLD had a hazard ratio of 1.58 (95% CI: 1.03-2.43) for incident AVC compared to those without NAFLD. After excluding genes associated with impaired VLDL secretion, the MR analyses consistently showed the significant associations between genetically predicted NAFLD and CAVS for 3 traits: chronic elevation of alanine aminotransferase (odds ratio = 1.13 [95% CI: 1.01-1.25]), imaging-based NAFLD (odds ratio = 2.81 [95% CI: 1.66-4.76]), and biopsy-confirmed NAFLD (odds ratio = 1.12 [95% CI: 1.01-1.24]). However, the association became non-significant when considering all NAFLD susceptibility genes. Conclusions: NAFLD was independently associated with an elevated risk of incident AVC. Genetically predicted NAFLD was also associated with CAVS after excluding genetic variants related to impaired VLDL secretion.

Small non-coding RNA signatures in atrial appendages of patients with atrial fibrillation.

The development of high-throughput technologies has enhanced our understanding of small non-coding RNAs (sncRNAs) and their crucial roles in various diseases, including atrial fibrillation (AF). This study aimed to systematically delineate sncRNA profiles in AF patients. PANDORA-sequencing was used to examine the sncRNA profiles of atrial appendage tissues from AF and non-AF patients. Differentially expressed sncRNAs were identified using the R package DEGseq 2 with a fold change >2 and p < 0.05. The target genes of the differentially expressed sncRNAs were predicted using MiRanda and RNAhybrid. Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. In AF patients, the most abundant sncRNAs were ribosomal RNA-derived small RNAs (rsRNAs), followed by transfer RNA-derived small RNAs (tsRNAs), and microRNAs (miRNAs). Compared with non-AF patients, 656 rsRNAs, 45 miRNAs, 191 tsRNAs and 51 small nucleolar RNAs (snoRNAs) were differentially expressed in AF patients, whereas no significantly differentially expressed piwi-interacting RNAs were identified. Two out of three tsRNAs were confirmed to be upregulated in AF patients by quantitative reverse transcriptase polymerase chain reaction, and higher plasma levels of tsRNA 5006c-LysCTT were associated with a 2.55-fold increased risk of all-cause death in AF patients (hazard ratio: 2.55; 95% confidence interval, 1.56-4.17; p < 0.001). Combined with our previous transcriptome sequencing results, 32 miRNA, 31 snoRNA, 110 nucleus-encoded tsRNA, and 33 mitochondria-encoded tsRNA target genes were dysregulated in AF patients. GO and KEGG analyses revealed enrichment of differentially expressed sncRNA target genes in AF-related pathways, including the 'calcium signaling pathway' and 'adrenergic signaling in cardiomyocytes.' The dysregulated sncRNA profiles in AF patients suggest their potential regulatory roles in AF pathogenesis. Further research is needed to investigate the specific mechanisms of sncRNAs in the development of AF and to explore potential biomarkers for AF treatment and prognosis.

Impact of varying dissolved organic carbon load on sediment phosphorus release and its periodic mechanisms.

Phosphorus (P) release from sediment poses a severe challenge for eutrophication management in the aquatic environment. The dissolved organic carbon (DOC) concentrations in riverine ecosystems have shown an increasing trend due to intensified climate change and anthropogenic activities, while their impact on sediment P cycling remains unclear. To investigate the effects of different DOC loads on sediment P release and the underlying mechanisms, we conducted a two-month experiment in 15 plexiglass tanks, with five gradient-increasing target DOC concentrations set according to reality: control (S0), 5 mg/L (S5), 10 mg/L (S10), 15 mg/L (S15), and 20 mg/L (S20). The results demonstrated that: i) DOC enrichment promoted the sediment P mobilization and release, with the underlying mechanisms exhibited periodic characteristics. ii) reduced dissolved oxygen (DO) concentration and stimulated alkaline phosphatase activity (APA) were likely the primary and sustained facilitating mechanisms. While after the termination of DOC load, elevated pH level was also considered a contributing factor when chlorophyll a (Chl a) ranged between 5.9 µg/L and 7.7 µg/L iii) ultimate concentration of total P (TP) in the overlying water depended on DOC load. After DOC addition was terminated, decreased TP concentrations were observed when DOC concentration was in the range of 5-15 mg/L, which may be attributed to the direct uptake of P by phytoplankton counteracting the minor promotion of P release induced by anoxic conditions. However, when DOC concentrations exceeded 15-20 mg/L, there were notable increments in TP concentrations. Our findings provide further insight into the response mechanisms of sediment P release to the increasing organic C load in natural ecosystems. The impact of broader C forms or C loads on sediment P cycling needs to be fully elucidated and even quantified in future studies, especially through large-scale field investigations to further clarify the coupled roles between C and P.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Cost-effectiveness of tirofiban for acute ischemic stroke without large or medium-sized vessel occlusion: A Markov modelling analysis from the Chinese and United States perspectives.

BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.

Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study.

BACKGROUND: Remnant cholesterol (RC) is implicated in the risk of cardiovascular disease. However, comprehensive population-based studies elucidating its association with aortic valve calcium (AVC) progression are limited, rendering its precise role in AVC ambiguous. METHODS: From the Multi-Ethnic Study of Atherosclerosis database, we included 5597 individuals (61.8 ± 10.1 years and 47.5% men) without atherosclerotic cardiovascular disease at baseline for analysis. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), as estimated by the Martin/Hopkins equation. Using the adjusted Cox regression analyses, we examined the relationships between RC levels and AVC progression. Furthermore, we conducted discordance analyses to evaluate the relative AVC risk in RC versus LDL-C discordant/concordant groups. RESULTS: During a median follow-up of 2.4 ± 0.9 years, 568 (10.1%) participants exhibited AVC progression. After adjusting for traditional cardiovascular risk factors, the HRs (95% CIs) for AVC progression comparing the second, third, and fourth quartiles of RC levels with the first quartile were 1.195 (0.925-1.545), 1.322 (1.028-1.701) and 1.546 (1.188-2.012), respectively. Notably, the discordant high RC/low LDL-C group demonstrated a significantly elevated risk of AVC progression compared to the concordant low RC/LDL-C group based on their medians (HR, 1.528 [95% CI 1.201-1.943]). This pattern persisted when clinical LDL-C threshold was set at 100 and 130 mg/dL. The association was consistently observed across various sensitivity analyses. CONCLUSIONS: In atherosclerotic cardiovascular disease-free individuals, elevated RC is identified as a residual risk for AVC progression, independent of traditional cardiovascular risk factors. The causal relationship of RC to AVC and the potential for targeted RC reduction in primary prevention require deeper exploration.

Age-dependent gender differences in the diagnosis and treatment of osteoporosis during hospitalization in patients with fragility fractures.

BACKGROUND: There is a gender difference in the acceptance of osteoporosis diagnosis and treatment in patients after fragility fractures, but this difference is rarely assessed during hospitalization, and it is unclear whether these differences are age-dependent. This study aimed to evaluate the differences between male and female fragility fracture patients of different age groups who received the diagnosis and treatment of osteoporosis during hospitalization. METHODS: 31,265 fragility fracture patients aged ≥ 50 years from the Fragility Fracture Management Database in a high-volume orthopedic hospital from December 2019 to February 2023 were included in this study. We compared the differences in the rates of men and women with fragility fracture who received the measurement of bone mineral density (BMD) and bone metabolism biochemical markers (BMBMs) and treatment with anti-osteoporosis medications (AOMs), and follow-up to the internal medicine clinic within 3 months after discharge, across all age groups and across different age stages (50-59, 60-69, 70-79, and ≥ 80 years). RESULTS: The detection rates of female patients receiving BMD and BMBMs during hospitalization were 31.88% and 5.30%, respectively, compared with 22.23% and 2.69% for men. The rate of receiving any AOMs treatment was 44.63% for women and 31.60% for men. The follow-up rate of returning to the internal medicine clinic within 3 months after discharge was 9.79% for women compared to 3.00% for men. There was a significant difference between males compared to females (P < 0.0001). Analysis of patients by different age group revealed that differences in the diagnosis and treatment of osteoporosis were found only in patients under 80 years of age, while gender differences in the return to the internal medicine clinic for follow-up after discharge were present in all age groups. CONCLUSIONS: Gender differences present in osteoporosis management in patients with fragility fracture during hospitalization, especially for patients under 80 years of age. This finding suggests that orthopedic surgeons neglect to manage osteoporosis in male patients with fragility fracture during hospitalization.

Effect of bedside health education for elderly patients with fragility fracture by specialist physicians on the diagnosis and treatment of osteoporosis during hospitalization and the visiting rate to osteoporosis clinic after discharge in a high-volume orthopedic hospital.

We retrospectively analyzed 12,999 elderly patients with fragility fracture and found that the detection rate of bone mineral density (BMD) and bone turnover markers (BTMs), the treatment rate of osteoporosis, and the visiting rate to the osteoporosis specialist clinic after discharge are significantly enhanced in fragility fracture patients after receiving health education on osteoporosis-related knowledge during hospitalization. PURPOSE: To observe the effect of health education on the diagnosis and treatment of osteoporosis during hospitalization and the rate of come back to osteoporosis clinic after discharge in elderly patients with fragility fracture. METHODS: A retrospective analysis was performed on 12,999 elderly patients with fragility fracture admitted to Xi'an Honghui Hospital from March 2021 to December 2022. The patients were divided into the health education group and the non-health education group according to whether they received health education on osteoporosis-related knowledge during hospitalization. The diagnosis and treatment of osteoporosis during hospitalization and the outpatient treatment of osteoporosis after discharge were compared between the two groups. RESULTS: Among the 7784 patients in the health education group, 4551 (58.47%) received BMD test, 798 (10.25%) received BTMs test, 3990 (51.26%) received anti-osteoporosis medications (AOMs) treatment, and 1232 (15.83%) came back to the osteoporosis specialist clinic after discharge. Among the 5215 patients in the non-health education group, 681 (13.06%) received BMD test, 6 (0.12%) received BTMs test, 2071 (39.71%) received AOMs treatment, and 440 (8.44%) came back to the osteoporosis specialist clinic within one month after discharge. CONCLUSION: The education of osteoporosis-related knowledge for patients with fragility fracture contribute to enhance the detection rate of BMD and BTMs and the treatment rate of osteoporosis during hospitalization, and increase the rate of coming back to the osteoporosis clinic after discharge.

Factors Associated With Delayed and Late Initiation of Antiretroviral Therapy Among Patients With HIV in Beijing, China, 2010-2020.

Objectives: To determine factors associated with late and delayed antiretroviral therapy (ART) initiation in China and provide evidence for HIV prevention. Methods: Logistics regression model was used to determine factors associated with three outcomes: late (CD4 cell count <200 cells/µL or clinical AIDS diagnosis prior to ART initiation), delayed (more than 1 month between HIV diagnosis date and ART initiation) and either late or delayed ART initiation. Results: Multivariable analysis revealed that male, heterosexual, HIV diagnosis before 2014, HBV/HCV seropositive, and tuberculosis were associated with increased odds of all three outcomes. Conversely, married or cohabiting patients were less likely to have delayed ART initiation and either late or delayed ART initiation, while people who inject drugs were more likely to have these two outcomes. Additionally, older age was associated with an increased risk of having either late or delayed ART initiation, but a decreased risk of delayed ART initiation. Conclusion: The proportion of late and delayed ART initiation decreased significantly after the release of the 2016 guidelines in China. To further improve late diagnosis and early treatment, precise interventions for key populations are required.

Preclinical Pharmacokinetic Study on Caffeine as an Excipient for Monoclonal Antibody Formulations.

Caffeine is a novel excipient that effectively reduces viscosity of high concentration mAb formulations intended for subcutaneous (SQ) delivery. Two preclinical studies were conducted in rats to evaluate pharmacokinetic (PK) parameters of caffeine as well as its effects on the PK profile of a model mAb, namely ipilimumab. Results show that SQ absorption and elimination of caffeine was rapid, with the average Tmax of 0.4 h and T1/2 of 1.6 h, administered with or without ipilimumab. Furthermore, caffeine did not affect ipilimumab SQ PK profiles. Independent of caffeine concentration, ipilimumab serum T1/2 was between 2 and 3 days, Tmax was between 3 and 4 days and SQ bioavailability was about 64%. In addition, SQ injection of caffeine at different dose levels showed no irritation at the injection site or adverse effects. Results from the current PK studies warrant further development of caffeine as a viscosity reducing excipient for mAb SQ formulations.

Identifying microbial signatures for patients with postmenopausal osteoporosis using gut microbiota analyses and feature selection approaches.

Osteoporosis (OP) is a metabolic bone disorder characterized by low bone mass and deterioration of micro-architectural bone tissue. The most common type of OP is postmenopausal osteoporosis (PMOP), with fragility fractures becoming a global burden for women. Recently, the gut microbiota has been connected to bone metabolism. The aim of this study was to characterize the gut microbiota signatures in PMOP patients and controls. Fecal samples from 21 PMOP patients and 37 controls were collected and analyzed using amplicon sequencing of the V3-V4 regions of the 16S rRNA gene. The bone mineral density (BMD) measurement and laboratory biochemical test were performed on all participants. Two feature selection algorithms, maximal information coefficient (MIC) and XGBoost, were employed to identify the PMOP-related microbial features. Results showed that the composition of gut microbiota changed in PMOP patients, and microbial abundances were more correlated with total hip BMD/T-score than lumbar spine BMD/T-score. Using the MIC and XGBoost methods, we identified a set of PMOP-related microbes; a logistic regression model revealed that two microbial markers (Fusobacteria and Lactobacillaceae) had significant abilities in disease classification between the PMOP and control groups. Taken together, the findings of this study provide new insights into the etiology of OP/PMOP, as well as modulating gut microbiota as a therapeutic target in the diseases. We also highlight the application of feature selection approaches in biological data mining and data analysis, which may improve the research in medical and life sciences.

Three-Dimensional Hounsfield Units Measurement of Pedicle Screw Trajectory for Predicating Screw Loosening in Lumbar Fusion Surgery.

Purpose: Dual-energy X-ray absorptiometry (DXA) is commonly used for evaluation of bone mineral density before spinal surgery, but frequently leads to overestimation in degenerative spinal diseases due to osteoproliferation factors. We introduce a novel method to compare the predictive ability of Hounsfield Units (HU) and DXA methods to predict screw loosening after lumbar interbody fusion surgery in degenerative spinal diseases by measuring HU of pedicle screw trajectory on computed tomography (CT) images preoperatively. Patients and Methods: This retrospective study was conducted on patients who underwent posterior lumbar fusion surgery for degenerative diseases. CT HUs measurement was performed using medical imaging software, including the cancellous region on cross-sections of the vertebral body and three-dimensional pedicle screw trajectory. Receiver operating characteristic (ROC) curve analyses were performed for the risk of pedicle screw loosening in association with the Hounsfield scale and preoperative BMD, and the area under the curve (AUC) and the cutoff values were calculated. Results: A total of 90 patients were enrolled and were divided into loosening (n = 33, 36.7%) and non-loosening groups (n = 57, 63.3%). No significant differences in age, gender, length of fixation and preoperative BMD were found between both groups. The loosening group showed lower CT HU values in the vertebral body and screw trajectory than the non-loosening group. Screw trajectory HU (ST-HU) exhibited a higher AUC value than vertebral body HU (B-HU). The cutoff values of B-HU and ST-HU were 160 and 110 HUs, respectively. Conclusion: Three-dimensional pedicle screw trajectory HU values yields a stronger predictive value than vertebral body HU values and BMD and may provide more guidance for surgery. The risk of screw loosening is significantly increased at ST-HU <110 or B-HU <160 at L5 segment.

Iron Deficiency and Iron Deficiency Anemia: Potential Risk Factors in Bone Loss.

Iron is one of the essential mineral elements for the human body and this nutrient deficiency is a worldwide public health problem. Iron is essential in oxygen transport, participates in many enzyme systems in the body, and is an important trace element in maintaining basic cellular life activities. Iron also plays an important role in collagen synthesis and vitamin D metabolism. Therefore, decrease in intracellular iron can lead to disturbance in the activity and function of osteoblasts and osteoclasts, resulting in imbalance in bone homeostasis and ultimately bone loss. Indeed, iron deficiency, with or without anemia, leads to osteopenia or osteoporosis, which has been revealed by numerous clinical observations and animal studies. This review presents current knowledge on iron metabolism under iron deficiency states and the diagnosis and prevention of iron deficiency and iron deficiency anemia (IDA). With emphasis, studies related to iron deficiency and bone loss are discussed, and the potential mechanisms of iron deficiency leading to bone loss are analyzed. Finally, several measures to promote complete recovery and prevention of iron deficiency are listed to improve quality of life, including bone health.

Non-coding RNA and arrhythmias: expression, function, and molecular mechanism.

Arrhythmias are a class of cardiac dysfunction characterized by heart rate disturbances and heart rhythm abnormalities, which are associated with substantial morbidity and mortality. Due to the limited understanding of pathological mechanism, current antiarrhythmic drugs and invasive therapies on arrhythmias lack sufficient efficacy and are always accompanied by potential adverse effects. Non-coding RNAs (including microRNAs, long non-coding RNAs, circular RNAs, and other small non-coding RNAs) have been demonstrated to be involved in the occurrence and development of various diseases including arrhythmias, which opens a new prospect for exploring the mechanism of arrhythmias and developing new therapeutic targets. Therefore, in this review, we aimed to provide an overview of the expression of ncRNAs in various arrhythmias, their roles in the arrhythmia's development and pathophysiology, and the potential mechanism of ncRNAs in arrhythmias. As atrial fibrillation (AF) is the most common arrhythmia in clinical practice and current studies mainly focus on it, this review primarily discussed about AF. It was expected that this review may provide a basis for a better understanding of the mechanistic role of ncRNAs in arrhythmias and facilitate the development of mechanic-based therapeutic targets.

Shared and distinct patterns of dynamic functional connectivity variability of thalamo-cortical circuit in bipolar depression and major depressive disorder.

Evidence has indicated abnormalities of thalamo-cortical functional connectivity (FC) in bipolar disorder during a depressive episode (BDD) and major depressive disorder (MDD). However, the dynamic FC (dFC) within this system is poorly understood. We explored the thalamo-cortical dFC pattern by dividing thalamus into 16 subregions and combining with a sliding-window approach. Correlation analysis was performed between altered dFC variability and clinical data. Classification analysis with a linear support vector machine model was conducted. Compared with healthy controls (HCs), both patients revealed increased dFC variability between thalamus subregions with hippocampus (HIP), angular gyrus and caudate, and only BDD showed increased dFC variability of the thalamus with superior frontal gyrus (SFG), HIP, insula, middle cingulate gyrus, and postcentral gyrus. Compared with MDD and HCs, only BDD exhibited enhanced dFC variability of the thalamus with SFG and superior temporal gyrus. Furthermore, the number of depressive episodes in MDD was significantly positively associated with altered dFC variability. Finally, the disrupted dFC variability could distinguish BDD from MDD with 83.44% classification accuracy. BDD and MDD shared common disrupted dFC variability in the thalamo-limbic and striatal-thalamic circuitries, whereas BDD exhibited more extensive and broader aberrant dFC variability, which may facilitate distinguish between these 2 mood disorders.

Insular-associated causal network of structural covariance evaluating progressive gray matter changes in major depressive disorder.

BACKGROUND: Morphometric studies demonstrated wide-ranging distribution of brain structural abnormalities in major depressive disorder (MDD). OBJECTIVE: This study explored the progressive gray matter volume (GMV) changes pattern of structural network in 108 MDD patients throughout the illness duration by using voxel-based morphometric analysis. METHODS: The causal structural covariance network method was applied to map the causal effects of GMV alterations between the original source of structural changes and other brain regions as the illness duration prolonged in MDD. This was carried out by utilizing the Granger causality analysis to T1-weighted data ranked based on the disease progression information. RESULTS: With greater illness duration, the GMV reduction was originated from the right insula and progressed to the frontal lobe, and then expanded to the occipital lobe, temporal lobe, dorsal striatum (putamen and caudate) and the cerebellum. Importantly, results revealed that the right insula was the prominent node projecting positive causal influences (i.e., GMV decrease) to frontal lobe, temporal lobe, postcentral gyrus, putamen, and precuneus. While opposite causal effects were detected from the right insula to the angular, parahippocampus, supramarginal gyrus and cerebellum. CONCLUSIONS: This work may provide further information and vital evidence showing that MDD is associated with progressive brain structural alterations.

Identification and Mapping of QTLs for Sulfur-Containing Amino Acids in Soybean (Glycine max L.).

Soybean is a major source of high-quality protein for humans and animals. The content of sulfur-containing amino acids (SAA) in soybean is insufficient, which has become the main factor limiting soybean nutrition. In this study, we used the high-density genetic maps derived from Guizao 1 and Brazil 13 to evaluate the quantitative trait loci of cysteine (Cys), methionine (Met), SAA, glycinin (7S), ß-conglycinin (11S), ratio of glycinin to ß-conglycinin (RGC), and protein content (PC). In genetic map linkage analysis, the major and stable 44 QTLs were detected, which shared nine bin intervals. Among them, the bin interval (bin157-bin160) on chromosome 5 was detected in multiple environments as a stable QTL, which was linked to 11S, 7S, RGC, and SSA. Based on the analysis of bioinformatics and RNA-sequencing data, 16 differentially expressed genes (DEGs) within these QTLs were selected as candidate genes. These results will help to elucidate the genetic mechanism of soybean SAA-related traits and provide the basis for the gene mining of sulfur-containing amino acids.

Evidence of the static magnetic field effects on bone-related diseases and bone cells.

Static magnetic fields (SMFs), magnetic fields with constant intensity and orientation, have been extensively studied in the field of bone biology both fundamentally and clinically as a non-invasive physical factor. A large number of animal experiments and clinical studies have shown that SMFs have effective therapeutic effects on bone-related diseases such as non-healing fractures, bone non-union of bone implants, osteoporosis and osteoarthritis. The maintenance of bone health in adults depends on the basic functions of bone cells, such as bone formation by osteoblasts and bone resorption by osteoclasts. Numerous studies have revealed that SMFs can regulate the proliferation, differentiation, and function of bone tissue cells, including bone marrow mesenchymal stem cells (BMSCs), osteoblasts, bone marrow monocytes (BMMs), osteoclasts, and osteocytes. In this paper, the effects of SMFs on bone-related diseases and bone tissue cells are reviewed from both in vivo studies and in vitro studies, and the possible mechanisms are analyzed. In addition, some challenges that need to be further addressed in the research of SMF and bone are also discussed.

Feature selection approaches identify potential plasma metabolites in postmenopausal osteoporosis patients.

INTRODUCTION: Postmenopausal women with osteoporosis (PMOP) are prone to fragility fractures. Osteoporosis is associated with alterations in the levels of specific circulating metabolites. OBJECTIVES: To analyze the metabolic profile of individuals with PMOP and identify novel metabolites associated with bone mineral density (BMD). METHODS: We performed an unsupervised metabolomics analysis of plasma samples from participants with PMOP and of normal controls (NC) with normal bone mass. BMD values for the lumber spine and the proximal femur were determined using dual-energy X-ray absorptiometry. Principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) were performed for metabolomic profile analyses. Metabolites with P < 0.05 in the t-test, VIP > 1 in the PLS-DA model, and SNR > 0.3 between the PMOP and NC groups were defined as differential abundant metabolites (DAMs). The SHapley additive explanations (SHAP) method was utilized to determine the importance of permutation of each DAM in the predictive model between the two groups. ROC analysis and correlation analysis of metabolite relative abundance and BMD/T-scores were conducted. KEGG pathway analysis was used for functional annotation of the candidate metabolites. RESULTS: Overall, 527 annotated molecular markers were extracted in the positive and negative total ion chromatogram (TIC) of each sample. The PMOP and NC groups could be differentiated using the PLS-DA model. Sixty-eight DAMs were identified, with most relative abundances decreasing in the PMOP samples. SHAP was used to identify 9 DAM metabolites as factors distinguishing PMOP from NC. The logistic regression model including Triethanolamine, Linoleic acid, and PC(18:1(9Z)/18:1(9Z)) metabolites demonstrated excellent discrimination performance (sensitivity = 97.0, specificity = 96.6, AUC = 0.993). The correlation analysis revealed that the abundances of Triethanolamine, PC(18:1(9Z)/18:1(9Z)), 16-Hydroxypalmitic acid, and Palmitic acid were significantly positively correlated with the BMD/T score (Pearson correlation coefficients > 0.5, P < 0.05). Most candidate metabolites were involved in lipid metabolism based on KEGG functional annotations. CONCLUSION: The plasma metabolomic signature of PMOP patients differed from that of healthy controls. Marker metabolites may help provide information for the diagnosis, therapy, and prevention of PMOP. We highlight the application of feature selection approaches in the analysis of high-dimensional biological data.