Diffusion Barrier Performance of Ni-W Layer at Sn/Cu Interfacial Reaction.

As the integration of chips in 3D integrated circuits (ICs) increases and the size of micro-bumps reduces, issues with the reliability of service due to electromigration and thermomigration are becoming more prevalent. In the practical application of solder joints, an increase in the grain size of intermetallic compounds (IMCs) has been observed during the reflow process. This phenomenon results in an increased thickness of the IMC layer, accompanied by a proportional increase in the volume of the IMC layer within the joint. The brittle nature of IMC renders it susceptible to excessive growth in small-sized joints, which has the potential to negatively impact the reliability of the welded joint. It is therefore of the utmost importance to regulate the formation and growth of IMCs. The following paper presents the electrodeposition of a Ni-W layer on a Cu substrate, forming a barrier layer. Subsequently, the barrier properties between the Sn/Cu reactive couples were subjected to a comprehensive and systematic investigation. The study indicates that the Ni-W layer has the capacity to impede the diffusion of Sn atoms into Cu. Furthermore, the Ni-W layer is a viable diffusion barrier at the Sn/Cu interface. The "bright layer" Ni2WSn4 can be observed in all Ni-W coatings during the soldering reflow process, and its growth was almost linear. The structure of the Ni-W layer is such that it reduces the barrier properties that would otherwise be inherent to it. This is due to the "bright layer" Ni2WSn4 that covers the original Ni-W barrier layer. At a temperature of 300 °C for a duration of 600 s, the Ni-W barrier layer loses its blocking function. Once the "bright layer" Ni2WSn4 has completely covered the original Ni-W barrier layer, the diffusion activation energy for Sn diffusion into the Cu substrate side will be significantly reduced, particularly in areas where the distortion energy is concentrated due to electroplating tension. Both the "bright layer" Ni2WSn4 and Sn will grow rapidly, with the formation of Cu-Sn intermetallic compounds (IMCs). At temperatures of 250 °C, the growth of Ni3Sn4-based IMCs is controlled by grain boundaries. Conversely, the growth of the Ni2WSn4 layer (consumption of Ni-W layer) is influenced by a combination of grain boundary diffusion and bulk diffusion. At temperatures of 275 °C and 300 °C, the growth of Ni3Sn4-based IMCs and the Ni2WSn4 layer (consumption of Ni-W layer) are both controlled by grain boundaries. The findings of this study can inform the theoretical design of solder joints with barrier layers as well as the selection of Ni-W diffusion barrier layers for use in different soldering processes. This can, in turn, enhance the reliability of microelectronic devices, offering significant theoretical and practical value.

Network pharmacology and experimental evidence: ERK/CREB/BDNF signaling pathway is involved in the antidepressive roles of Kaiyu Zhishen decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.

Interferon Regulatory Factor 4 (IRF4) Plays a Key Role in Osteoblast Differentiation of Postmenopausal Osteoporosis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a prevalent disease, which features decreased bone mass, bone weakness and deteriorated bone microstructure in postmenopausal women. Although many factors have been revealed to contribute to the occurrence of PMOP, its mechanism remains undefined. This work aimed to identify significant changes in gene expression during PMOP formation and to examine the most valuable differential genes in postmenopausal osteoporosis versus the control group. METHODS: The GSE68303 dataset that contains 12 ovariectomize (OVX) experimental and 11 sham groups was downloaded and analyzed. The results indicated that interferon regulatory factor 4 (IRF4) might be a hub gene in the development of postmenopausal osteoporosis. Western blot and immunohistochemistry were carried out to evaluate IRF4 levels in thoracic vertebra extracts from OVX and Sham mice. To assess IRF4's impact on osteogenic differentiation in postmenopausal bone marrow mesenchymal stem cells (BM-MSCs), IRF4 overexpression (OV-IRF4) and knockdown (Sh-IRF4) plasmids were constructed. RESULTS: The results showed that comparing with the sham group, bone samples from the OVX group showed higher IRF4 expression. Alkaline phosphatase (ALP) staining revealed that IRF4 overexpression significantly inhibited ALP activity, while IRF4 knockdown promoted ALP activity in BM-MSCs. Simvastatin-treated OVX mice showed increased total bone volume/total tissue volume (BV/TV) and elevated Runx2 expression by immunohistochemical staining compared with the OVX group. CONCLUSIONS: This study demonstrated that IRF4 is associated with OVX induced osteoporosis, it can regulate bone stability by inhibiting the osteogenic differentiation BM-MSCs. This study may help enhance our understanding of the molecular mechanism of PMOP formation, providing new insights into estrogen defiance induced osteoporosis.

Daoyin therapy in chronic neck pain: study protocol for a randomized controlled trial.

BACKGROUND: Daoyin therapy (DT), an ancient therapeutic approach with a history spanning thousands of years, has traditionally been employed to address musculoskeletal pain and psychosomatic disorders. However, the application of DT for chronic neck pain (CNP) has received limited attention in the existing literature, and systematic randomized clinical trials (RCTs) in this context remain scarce. This manuscript outlines an RCT protocol designed to investigate whether DT is more effective at alleviating CNP in adult individuals compared to other interventions. METHODS: A 12-week RCT was conducted, with participants undergoing randomization into one of three groups: DT, Meditation + Fitness Exercise (M+FE), or a control group. Participants in the DT and M + FE groups attended their respective training classes three times per week for 12 weeks. Participants in the control group were required to attend health education workshops every 2 weeks. Following the 12-week intervention period, all participants underwent follow-up assessments at the 16th week. Outcome measures encompassed the Simplified Chinese Neck Pain and Disability Scale (SC-NPAD) and Visual Analog Scale (VAS) for pain assessment, Static Neck Posture Assessment (SNPA) to evaluate neck and shoulder posture and function, Short Form-36 (SF-36) to assess quality of life, and blood tests measuring 5-Hydroxytryptamine (5-HT), Norepinephrine/Noradrenaline (NE/NA), γ-aminobutyric acid (GABA), Adreno-Cortico-Tropic-Hormone (ACTH), ß-Endorphin (ß-EP), and Calcitonin-Gene-Related Peptide (CGRP) levels via high-performance liquid chromatography (HPLC), chemiluminescence immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). Brain activity changes were monitored through MRI scans. Repeated measures analyses of variance (ANOVAs) will be used to evaluate the outcomes at baseline, at the 12th week, and at the 16th week. Generalized Estimating Equation (GEE) models will be applied to analyze changes in outcomes over time and differences between groups. DISCUSSION: This trial aims to evaluate the efficacy of DT in comparison to other interventions and explore the neuroendocrine mechanisms underlying its effects in adults with CNP. If the intervention and procedures demonstrate feasibility and acceptability, there are plans to conduct a more extensive controlled trial. This could potentially pave the way for the broader application of DT, not only in the context of CNP but also for other chronic diseases. TRIAL REGISTRATION: This trial has been registered with the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400079571]).

[Application and prospect of machine learning in orthopaedic trauma].

Objective: To review the current applications of machine learning in orthopaedic trauma and anticipate its future role in clinical practice. Methods: A comprehensive literature review was conducted to assess the status of machine learning algorithms in orthopaedic trauma research, both nationally and internationally. Results: The rapid advancement of computer data processing and the growing convergence of medicine and industry have led to the widespread utilization of artificial intelligence in healthcare. Currently, machine learning plays a significant role in orthopaedic trauma, demonstrating high performance and accuracy in various areas including fracture image recognition, diagnosis stratification, clinical decision-making, evaluation, perioperative considerations, and prognostic risk prediction. Nevertheless, challenges persist in the development and clinical implementation of machine learning. These include limited database samples, model interpretation difficulties, and universality and individualisation variations. Conclusion: The expansion of clinical sample sizes and enhancements in algorithm performance hold significant promise for the extensive application of machine learning in supporting orthopaedic trauma diagnosis, guiding decision-making, devising individualized medical strategies, and optimizing the allocation of clinical resources.

Machine learning applications for the prediction of extended length of stay in geriatric hip fracture patients.

BACKGROUND: Geriatric hip fractures are one of the most common fractures in elderly individuals, and prolonged hospital stays increase the risk of death and complications. Machine learning (ML) has become prevalent in clinical data processing and predictive models. This study aims to develop ML models for predicting extended length of stay (eLOS) among geriatric patients with hip fractures and to identify the associated risk factors. AIM: To develop ML models for predicting the eLOS among geriatric patients with hip fractures, identify associated risk factors, and compare the performance of each model. METHODS: A retrospective study was conducted at a single orthopaedic trauma centre, enrolling all patients who underwent hip fracture surgery between January 2018 and December 2022. The study collected various patient characteristics, encompassing demographic data, general health status, injury-related data, laboratory examinations, surgery-related data, and length of stay. Features that exhibited significant differences in univariate analysis were integrated into the ML model establishment and subsequently cross-verified. The study compared the performance of the ML models and determined the risk factors for eLOS. RESULTS: The study included 763 patients, with 380 experiencing eLOS. Among the models, the decision tree, random forest, and extreme Gradient Boosting models demonstrated the most robust performance. Notably, the artificial neural network model also exhibited impressive results. After cross-validation, the support vector machine and logistic regression models demonstrated superior performance. Predictors for eLOS included delayed surgery, D-dimer level, American Society of Anaesthesiologists (ASA) classification, type of surgery, and sex. CONCLUSION: ML proved to be highly accurate in predicting the eLOS for geriatric patients with hip fractures. The identified key risk factors were delayed surgery, D-dimer level, ASA classification, type of surgery, and sex. This valuable information can aid clinicians in allocating resources more efficiently to meet patient demand effectively.

Relationships among body weight, lipids and bone mass in elderly individuals with fractures: A case-control study.

BACKGROUND: The prevalence of osteoporosis and low bone mass is steadily rising each year. Low body weight is commonly linked to diminished bone mass and serves as a robust predictor of osteoporosis. Nonetheless, the connection between body mass index (BMI), bone mineral density, and lipid profiles among the elderly remains elusive. AIM: To examine the association between BMI and bone mass, explore the correlation between lipid profiles and bone mass, and delve into the interplay between lipid metabolism and bone health. METHODS: The study included 520 patients aged ≥ 65 years (178 men and 342 women). Age, sex, weight, and height were recorded. Femoral neck bone mineral density and T scores were determined using a dual-energy X-ray absorptiometry scanner. Blood calcium (Ca), phosphorus (P), albumin (ALB), alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured. Patients were classified by sex (male and female), age (65-79 years and ≥ 80 years), and T score (normal bone mineral density, osteopenia and osteoporosis). RESULTS: Age, sex, BMI, and ALP and TG levels were independent risk factors for osteoporosis. For the 65-79- and ≥ 80-year-old groups, females presented lower T scores than males. Ca, P, ALB, ALP, TC, HDL and LDL levels were significantly different between men and women in the 65-79-year-old group. In addition, BMI and TG levels were significantly decreased in osteoporotic patients compared with patients with normal bone mass. TC levels declined in 65- to 79-year-old male and female osteoporosis patients. In the group of women aged ≥ 80 years, osteoporotic patients showed significantly increased ALP levels. Furthermore, we found positive correlations between BMI and TG levels in the male and female patient groups. However, we found no significant differences in ALB, Ca, P, HDL and LDL levels in osteoporotic patients compared to patients with normal bone mass. CONCLUSION: Osteoporotic patients showed significantly decreased BMI and TG levels compared with those with normal bone mass. BMI showed positive correlations with TG levels in male and female patients. These results indicate correlations between BMI and bone mass and between lipid profiles and bone mass.

Does PM1 exposure during pregnancy impact the gut microbiota of mothers and neonates?

BACKGROUND: Ambient air pollutant exposure can change the composition of gut microbiota at 6-months of age, but there is no epidemiological evidence on the impacts of exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during pregnancy on gut microbiota in mothers and neonates. We aimed to determine if gestational PM1 exposure is associated with the gut microbiota of mothers and neonates. METHODS: Leveraging a mother-infant cohort from the central region of China, we estimated the exposure concentrations of PM1 during pregnancy based on residential address records. The gut microbiota of mothers and neonates was analyzed using 16 S rRNA V3-V4 gene sequences. Functional pathway analyses of 16 S rRNA V3-V4 bacterial communities were conducted using Tax4fun. The impact of PM1 exposure on α-diversity, composition, and function of gut microbiota in mothers and neonates was evaluated using multiple linear regression, controlling for nitrogen dioxide (NO2) and ozone (O3). Permutation multivariate analysis of variance (PERMANOVA) was used to analyze the interpretation degree of PM1 on the sample differences at the OTU level using the Bray-Curtis distance algorithm. RESULTS: Gestational PM1 exposure was positively associated with the α-diversity of gut microbiota in neonates and explained 14.8% (adj. P = 0.026) of the differences in community composition among neonatal samples. In contrast, gestational PM1 exposure had no impact on the α- and ß-diversity of gut microbiota in mothers. Gestational PM1 exposure was positively associated with phylum Actinobacteria of gut microbiota in mothers, and genera Clostridium_sensu_stricto_1, Streptococcus, Faecalibacterium of gut microbiota in neonates. At Kyoto Encyclopedia of Genes and Genomes pathway level 3, the functional analysis results showed that gestational PM1 exposure significantly down-regulated Nitrogen metabolism in mothers, as well as Two-component system and Pyruvate metabolism in neonates. While Purine metabolism, Aminoacyl-tRNA biosynthesis, Pyrimidine metabolism, and Ribosome in neonates were significantly up-regulated. CONCLUSIONS: Our study provides the first evidence that exposure to PM1 has a significant impact on the gut microbiota of mothers and neonates, especially on the diversity, composition, and function of neonatal meconium microbiota, which may have important significance for maternal health management in the future.

Is There a "Black Friday" for Geriatric Hip Fracture Surgery?

OBJECTIVES: Reports show an increase in the short-term mortality rates of hip fracture patients admitted on weekends. However, there are few studies on whether there is a similar effect in Friday admissions of geriatric hip fracture patients. The aim of this study was to evaluate the effects of Friday admission on mortality and clinical outcomes in elderly patients with hip fractures. METHODS: A retrospective cohort study was performed at a single orthopaedic trauma centre and included all patients who underwent hip fracture surgery between January 2018 and December 2021. Patient characteristics, including age, sex, BMI, fracture type, time of admission, ASA grade, comorbidities, and laboratory examinations, were collected. Data pertaining to surgery and hospitalization were extracted from the electronic medical record system and tabulated. The corresponding follow-up was performed. The Shapiro-Wilk test was applied to evaluate the distributions of all continuous variables for normality. The overall data were analyzed by Student's t test or the Mann-Whitney U test for continuous variables and the chi-square test for categorical variables, as appropriate. Univariate and multivariate analyses were used to further test for the independent influencing factors of prolonged time to surgery. RESULTS: A total of 596 patients were included, and 83 patients (13.9%) were admitted on Friday. There was no evidence supporting that Friday admission had an effect on mortality and outcomes, including length of stay, total hospital costs and postoperative complications. However, the patients admitted on Friday had delayed surgery. Then, patients were regrouped into two groups according to whether surgery was delayed, and 317 patients (53.2%) underwent delayed surgery. The multivariate analysis showed that younger age (p = 0.014), Friday admission (p < 0.001), ASA classification III-IV (p = 0.019), femoral neck fracture (p = 0.002), time from injury to admission more than 24 h (p = 0.025), and diabetes (p = 0.023) were risk factors for delayed surgery. CONCLUSIONS: Mortality and adverse outcome rates for elderly hip fracture patients admitted on Friday were similar to those admitted at other time periods. However, Friday admission was identified as one of the risk factors for delayed surgery.

The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: ingenious involvement of gut microbiota and its metabolites.

Osteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.

Is the Gestational Weight Gain Recommended by the National Academy of Medicine Guidelines Suitable for Chinese Twin-Pregnant Women with Gestational Diabetes Mellitus?

OBJECTIVES: This study aimed to assess the applicability of the National Academy of Medicine (NAM) interim guidelines for twin pregnancies to the specific population of gestational diabetes mellitus by exploring the relationship between gestational weight gain and adverse pregnancy outcomes in Chinese twin-pregnant women with gestational diabetes mellitus. STUDY DESIGN: This was a retrospective cohort study of women diagnosed with diabetes in pregnancy between July 2017 and December 2020 at the Maternal and Child Health Hospital in Chongqing, China. The primary variable of interest was maternal total gestational weight gain. The primary outcomes were perinatal outcomes, which included: preeclampsia, small for gestational age, large for gestational age, low birth weight, neonatal pneumonia, neonatal respiratory distress syndrome, and neonatal intensive unit admission, etc. The association between inappropriate gestational weight gain and adverse pregnancy outcomes was estimated using multiple logistic regression analysis. RESULTS: A total of 455 twin-pregnant women who had gestational diabetes mellitus were analyzed. Women with low gestational weight gain had reduced risk of preeclampsia (adjusted odds ratio [aOR], 0.32; 95% CI or confidence interval, 0.17-0.63; p = 0.001) and their infants had higher risks of small for gestational age (aOR, 1.93; 95% CI, 1.04-3.58; p = 0.037), low birth weight (aOR, 2.27; 95% CI, 1.32-3.90; p = 0.003), neonatal intensive unit admission (aOR, 3.29; 95% CI, 1.10-5.78; p = 0.038), pneumonia (aOR, 2.41; 95% CI, 1.08-5.33; p = 0.031), and neonatal respiratory distress syndrome (aOR, 2.29; 95% CI, 1.10-4.78; p = 0.027); the infants of women with excessive gestational weight gain had a higher risk of large for gestational age (aOR, 3.76; 95% CI, 1.42-9.96; p = 0.008). CONCLUSION: Gestational weight gain controlled within the range recommended by the NAM could reduce the risk of perinatal adverse outcomes. The 2009 NAM gestational weight gain recommendations can be used for Chinese twin-pregnant women with gestational diabetes mellitus. KEY POINTS: · Inappropriate gestational weight gain can lead to adverse perinatal outcomes in twin pregnancies.. · Gestational weight gain controlled within recommended range could reduce the risk of poor perinatal outcomes.. · The National Academy of Medicine recommendations are suitable for Chinese twin-pregnant women with GDM..

Psychometric evaluation of the body understanding measure pregnancy scale Chinese version for pregnant Chinese women.

OBJECTIVES: At present, there is limited research on pregnancy body image and no valid tool to measure body image in pregnant Chinese women. The purpose of this study was to translate the Body Understanding Measure Pregnancy Scale into Chinese to determine its reliability and validity in measuring body image in pregnant women. METHODS: The translation of the Body Understanding Measure Pregnancy Scale (BUMPs) was carried out with a standardized procedure. This study was conducted from July to December 2020 in the outpatient department of three tertiary hospitals in China. There were 1069 pregnant women completed the questionnaire and 1057 of those women were included in the analysis. Internal consistency, test-retest reliability, content validity, and construct validity of the translation version were examined. RESULTS: The final Chinese version of the BUMPs (BUMPs-C) had four dimensions with 16 items. Exploratory factor analysis obtained a three-factor solution, which explained 50.26% of the total variances. Confirmatory factor analysis showed that the model fit of the four-factor model was better than the three-factor model, and the four-factor model also reached a satisfactory model fit after modifying: Minimum Discrepancy was 2.82; Comparative Fit Index was 0.939, and Tucker-Lewis Index was 0.92; Root Mean Square Error of Approximation was 0.059. The content validity index of the scale was 1.0; the Cronbach's alpha (α) coefficient was 0.82 for the total scale, the McDonald's omega (ω) coefficient was 0.829; the test-retest reliability was 0.796. CONCLUSIONS: The BUMPs-C showed good reliability and validity among pregnant Chinese women, which can be used as a simple and valid measurement tool to assess the feelings of pregnant Chinese women on body changes during pregnancy.

Inhibition of Microbiota-dependent Trimethylamine N-Oxide Production Ameliorates High Salt Diet-Induced Sympathetic Excitation and Hypertension in Rats by Attenuating Central Neuroinflammation and Oxidative Stress.

Excessive dietary salt intake induces neuroinflammation and oxidative stress in the brain, which lead to sympathetic excitation, contributing to hypertension. However, the underlying mechanisms remain elusive. Accumulating evidence reveals that trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite, is implicated in the pathogenesis of multiple cardiovascular diseases. The present study sought to determine whether central TMAO is elevated and associated with neuroinflammation and oxidative stress in the brain after long-term high salt (HS) diet intake and, if so, whether inhibition of TMAO generation ameliorates HS-induced sympathetic excitation and hypertension. Sprague-Dawley rats were fed either a HS diet or a normal salt (NS) diet and simultaneously treated with vehicle (VEH) or 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) for 8 weeks. HS + VEH rats, compared with NS + VEH rats, had elevated TMAO in plasma and cerebrospinal fluid (CSF), increased blood pressure (BP), and increased sympathetic drive as indicated by the BP response to ganglionic blockade and plasma norepinephrine levels. HS-induced these changes were attenuated by DMB, which significantly reduced TMAO in plasma and CSF. Neuroinflammation as assessed by proinflammatory cytokine expression and NF-κB activity and microglial activity, and oxidative stress as measured by NAD(P)H oxidase subunit expression and NAD(P)H activity and reactive oxygen species (ROS) production in the hypothalamic paraventricular nucleus (PVN) were increased in HS + VEH rats but were decreased by DMB. DMB had no effects on above measured parameters in NS rats. The results suggest that long-term HS diet intake causes elevation in TMAO in the circulation and brain, which is associated with increased neuroinflammation and oxidative stress in the PVN, an important cardiovascular regulatory center. Inhibition of TMAO generation ameliorates HS-induced sympathetic excitation and hypertension by reducing neuroinflammation and oxidative stress in the PVN.

Osteoblast lineage Sod2 deficiency leads to an osteoporosis-like phenotype in mice.

Osteoporosis is a systemic metabolic skeletal disease characterized by low bone mass and strength associated with fragility fractures. Oxidative stress, which results from elevated intracellular reactive oxygen species (ROS) and arises in the aging organism, is considered one of the critical factors contributing to osteoporosis. Mitochondrial (mt)ROS, as the superoxide anion (O2-) generated during mitochondrial respiration, are eliminated in the young organism by antioxidant defense mechanisms, including superoxide dismutase 2 (SOD2), the expression and activity of which are decreased in aging mesenchymal progenitor cells, accompanied by increased mtROS production. Using a mouse model of osteoblast lineage cells with Sod2 deficiency, we observed significant bone loss in trabecular and cortical bones accompanied by decreased osteoblast activity, increased adipocyte accumulation in the bone marrow and augmented osteoclast activity, suggestive of altered mesenchymal progenitor cell differentiation and osteoclastogenesis. Furthermore, osteoblast senescence was increased. To date, there are only a few studies suggesting a causal association between mtROS and cellular senescence in tissue in vivo. Targeting SOD2 to improve redox homeostasis could represent a potential therapeutic strategy for maintaining bone health during aging.

Effects of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus.

AIM: To explore the effect of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus (GDM). METHODS: This retrospective study reviewed the medical records of women with GDM delivered at the Chongqing Maternal and Child Health Hospital in China between July 2017 and December 2020. The live singleton pregnancies with α or ß-thalassemia were identified as the thalassemia group, included α-thalassemia subgroup and ß-thalassemia subgroup, whereas pregnant women without thalassemia were randomly selected as the non-thalassemia group according to a control-to-case ratio of 10:1 by computerized randomization. Logistic regression analyses were used to explore the potential association between thalassemia and pregnancy outcomes. RESULTS: A total of 223 pregnant women with GDM and thalassemia were analyzed, including women with α-thalassemia (n = 143) and ß-thalassemia (n = 80). There were no significant differences in the incidence of adverse neonatal outcomes such as preterm birth and low-birth weight among groups. However, among pregnancy complications, significant differences were detected in the incidence of placenta increta, polyhydramnios, and postpartum anemia between the thalassemia group and the non-thalassemia group. Logistic regression results indicated that ß-thalassemia increased the risk of polyhydramnios (odds ratio [OR] = 3.95, 95% confidence interval [CI]: 1.14-13.65, p = 0.030) and chorioamnionitis (OR = 3.61, 95%CI: 1.04-12.49, p = 0.043) compared with the non-thalassemia group. CONCLUSION: In our study, thalassemia did not increase adverse neonatal outcomes, but ß-thalassemia increased the risk of pregnancy complications, including polyhydramnios and chorioamnionitis.

Modified sinus tarsi approach with a variable-angle locking anterolateral plate for Sanders type II and III calcaneal fractures.

BACKGROUND: We compared the effectiveness of the extensile lateral approach (ELA) and modified sinus tarsi approach (MSTA) with a variable-angle locking anterolateral plate in treating Sanders type II and III calcaneal fractures. METHODS: We reviewed 45 DIACFs treated by a single surgeon from 2017 to 2020. Open reduction using ELA and MSTA was performed in 25 and 20 patients, respectively. Follow-up evaluations included radiological assessments and clinical evaluations. RESULTS: Pre- and postoperative radiologic parameters for the calcaneus were significantly different. The average American Orthopaedic Foot and Ankle Society scores were 81.24 and 85.00, the mean visual analogue scale scores were 2.28 and 1.65, and the wound-related complication rates were 64.0% and 15.0% in the ELA and MSTA groups, respectively. Bony union was achieved in all cases. CONCLUSIONS: For Sanders type II and III fractures, MSTA seems to be a safer and more satisfactory method, with fewer postoperative complications.

Exploring the experience of nursing undergraduates in using gamification teaching mode based on the flow theory in nursing research: A qualitative study.

BACKGROUND: With the development of evidence-based nursing practice, nursing research courses are important in undergraduate programs. However, nursing research courses are highly theoretical, which is difficult for students to understand. Improving the teaching quality of nursing research courses is a challenge for educators. OBJECTIVES: To understand the learning experience and the effect of gamification teaching on nursing undergraduates, and to provide new ideas for nurse educators. DESIGN: A qualitative research design using individual semi-structured interviews. SETTINGS: Gamification teaching was applied in an undergraduate nursing research course over one semester at a university in Central China. PARTICIPANTS: Purposive sampling was adopted to select nine undergraduate nursing students who had recently completed gamification teaching in a nursing research course. METHODS: Data were collected through semi-structured interviews and analyzed using Colaizzi's phenomenological method. RESULTS: Three major themes and seven subthemes emerged from the interviewees' experience: (1) positive attitude (e.g., acceptance with pleasure and flow experience); (2) self-perceived competence improvement (e.g., creative thinking, collaboration, and knowledge internalization and application); and (3) challenges of gamification teaching (e.g., learning pressure and rationality of game design). CONCLUSIONS: The gamification teaching mode based on the flow theory had a positive effect on the students' learning experience in the nursing research course. It is recommended to improve the game design model and to enhance its effectiveness for classrooms in the future.

The modulatory effect and implication of gut microbiota on osteoporosis: from the perspective of "brain-gut-bone" axis.

Osteoporosis (OP) is a kind of systemic metabolic disease characterized by decreased bone mass and destruction of the bone microstructure. In recent years, it has become an expected research trend to explore the cross-linking relationship in the pathogenesis process of OP so as to develop reasonable and effective intervention strategies. With the further development of intestinal microbiology and the profound exploration of the gut microbiota (GM), it has been further revealed that the "brain-gut" axis may be a potential target for the bone, thereby affecting the occurrence and progression of OP. Hence, based on the concept of "brain-gut-bone" axis, we look forward to deeply discussing and summarizing the cross-linking relationship of OP in the next three parts, including the "brain-bone" connection, "gut-bone" connection, and "brain-gut" connection, so as to provide an emerging thought for the prevention strategies and mechanism researches of OP.

MiR-421 promotes the development of osteosarcoma by regulating MCPIP1 expression.

Despite improvements in surgical resection and adjuvant chemotherapy, the prognosis and outcomes of patients with osteosarcoma remains poor due to the occurrence of metastasis or relapse. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1), a zinc-finger RNA-binding protein, is known to regulate inflammatory responses and repress breast cancer growth. However, the regulation of MCPIP1 by microRNAs has not been clearly elucidated in osteosarcoma. In this study, we found that miR-421 expression was upregulated and MCPIP1 expression was downregulated in the osteosarcoma specimens from patients. Moreover, MCPIP1 expression was inversely correlated with miR-421 expression in the clinical samples. Furthermore, the upregulation of miR-421 and downregulation of MCPIP1 resulted in poor overall survival and severe disease progression, respectively, in the patients with osteosarcoma. Bioinformatics analysis and luciferase reporter gene assays confirmed that miR-421 specifically targets and binds to the 3'-UTR of MCPIP1. The overexpression of miR-421 induced cell proliferation, invasion, and migration, and the release of pro-inflammatory IL-6 in cultured human osteosarcoma cells. Additionally, the administration of miR-421 to tumor-bearing mice facilitated osteosarcoma growth by downregulating MCPIP1 expression. Taken together, these findings indicate that miR-421 is able to promote the development of osteosarcoma by regulating MCPIP1 expression, and can be a potential therapeutic target for osteosarcoma.