Identification of Potential Causal Genes for Neurodegenerative Diseases by Mitochondria-Related Genome-Wide Mendelian Randomization.

Current research lacks comprehensive investigations into the potential causal link between mitochondrial-related genes and the risk of neurodegenerative diseases (NDDs). We aimed to identify potential causative genes for five NDDs through an examination of mitochondrial-related gene expression levels. Through the integration of summary statistics from expression quantitative trait loci (eQTL) datasets (human blood and brain tissue), mitochondrial DNA copy number (mtDNA-CN), and genome-wide association studies (GWAS) datasets of five NDDs from European ancestry, we conducted a Mendelian randomization (MR) analysis to explore the potential causal relationship between mitochondrial-related genes and Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Sensitivity analysis and Bayesian colocalization were employed to validate this causal relationship. Through MR analysis, we have identified potential causal relationships between 12 mitochondria-related genes and AD, PD, ALS, and FTD overlapping with motor neuron disease (FTD_MND) in human blood or brain tissue. Bayesian colocalization analysis further confirms 9 causal genes, including NDUFS2, EARS2, and MRPL41 for AD; NDUFAF2, MALSU1, and METTL8 for PD; MYO19 and MRM1 for ALS; and FASTKD1 for FTD_MND. Importantly, in both human blood and brain tissue, NDUFS2 exhibits a significant pathogenic effect on AD, while NDUFAF2 demonstrates a robust protective effect on PD. Additionally, the mtDNA-CN plays a protected role in LBD (OR = 0.62, p = 0.031). This study presents evidence establishing a causal relationship between mitochondrial dysfunction and NDDs. Furthermore, the identified candidate genes may serve as potential targets for drug development aimed at preventing NDDs.

Magnetic conjugated microporous polymer for rapid extraction and sensitive analysis of environmental endocrine disruptors in environmental waters and dairy products.

BACKGROUND: Environmental endocrine disruptors (EEDs) are a class of new pollutants that are diffusely used in the medical industry and animal husbandry. In view of toxicity concerns, elevated levels of EEDs in the environment and food, which cause potential harm to human beings and ecosystems, must be monitored. Determination of EEDs contaminants to ensure environment and food safety has became a major concern worldwide, it is also a challenging task because of their trace level and probable matrices interference. Thus, developing rapid adsorption and efficient analysis methods for EEDs is apparently necessary. RESULTS: A magnetic conjugated micro-porous polymer (Fe3O4@TbDt) was designed and synthesized, which was endowed with large specific surface area, rich functional groups and magnetic responsiveness. The material showed high extraction efficiency for EEDs via magnetic solid-phase extraction (MSPE). The quantum chemistry calculations showed the adsorption mechanism of Fe3O4@TbDt on EEDs mainly included electrostatic interactions, van der waals forces (N-H … π interaction, C-H … π interaction), and multiple hydrogen bonds. Finally, a trace analysis method for nine EEDs was established combined with HPLC-MS/MS under optimized MSPE conditions. The method showed a good linearity (R2 ≥ 0.996), low limits of detection (0.25-5.1 ng L-1), high precision (RSD of 1.1-8.2 %, n = 6). The applicability of this method was investigated by analyzing four water samples and two dairy products, and satisfactory recovery rates (82.1-100.7 %) were obtained. The proposed method showed the potential for the analysis of EEDs residues in food and environmental samples. SIGNIFICANCE: The developed MSPE method based on conjugated micro-porous polymers (CMPs) is simple, green, and efficient compared to existing techniques. The application of CMPs provides a new idea for preparing versatile sample pre-treatment materials. What's more, this work has certain reference value for addressing of EEDs residues in the environment and food.

Systematic druggable genome-wide Mendelian randomization identifies therapeutic targets for sarcopenia.

BACKGROUND: There are no effective pharmacological treatments for sarcopenia. We aim to identify potential therapeutic targets for sarcopenia by integrating various publicly available datasets. METHODS: We integrated druggable genome data, cis-eQTL/cis-pQTL from human blood and skeletal muscle tissue, and GWAS summary data of sarcopenia-related traits to analyse the potential causal relationships between drug target genes and sarcopenia using the Mendelian Randomization (MR) method. Sensitivity analyses and Bayesian colocalization were employed to validate the causal relationships. We also assessed the side effects or additional indications of the identified drug targets using a phenome-wide MR (Phe-MR) approach and investigated actionable drugs for target genes using available databases. RESULTS: MR analysis identified 17 druggable genes with potential causation to sarcopenia in human blood or skeletal muscle tissue. Six of them (HP, HLA-DRA, MAP 3K3, MFGE8, COL15A1, and AURKA) were further confirmed by Bayesian colocalization (PPH4 > 90%). The up-regulation of HP [higher ALM (beta: 0.012, 95% CI: 0.007-0.018, P = 1.2*10-5) and higher grip strength (OR: 0.96, 95% CI: 0.94-0.98, P = 4.2*10-5)], MAP 3K3 [higher ALM (beta: 0.24, 95% CI: 0.21-0.26, P = 1.8*10-94), higher grip strength (OR: 0.82, 95% CI: 0.75-0.90, P = 2.1*10-5), and faster walking pace (beta: 0.03, 95% CI: 0.02-0.05, P = 8.5*10-6)], and MFGE8 [higher ALM (muscle eQTL, beta: 0.09, 95% CI: 0.06-0.11, P = 6.1*10-13; blood pQTL, beta: 0.05, 95% CI: 0.03-0.07, P = 3.8*10-09)], as well as the down-regulation of HLA-DRA [lower ALM (beta: -0.09, 95% CI: -0.11 to -0.08, P = 5.4*10-36) and lower grip strength (OR: 1.13, 95% CI: 1.07-1.20, P = 1.8*10-5)] and COL15A1 [higher ALM (muscle eQTL, beta: -0.07, 95% CI: -0.10 to -0.04, P = 3.4*10-07; blood pQTL, beta: -0.05, 95% CI: -0.06 to -0.03, P = 1.6*10-07)], decreased the risk of sarcopenia. AURKA in blood (beta: -0.16, 95% CI: -0.22 to -0.09, P = 2.1*10-06) and skeletal muscle (beta: 0.03, 95% CI: 0.02 to 0.05, P = 5.3*10-05) tissues showed an inverse relationship with sarcopenia risk. The Phe-MR indicated that the six potential therapeutic targets for sarcopenia had no significant adverse effects. Drug repurposing analysis supported zinc supplementation and collagenase clostridium histolyticum might be potential therapeutics for sarcopenia by activating HP and inhibiting COL15A1, respectively. CONCLUSIONS: Our research indicated MAP 3K3, MFGE8, COL15A1, HP, and HLA-DRA may serve as promising targets for sarcopenia, while the effectiveness of zinc supplementation and collagenase clostridium histolyticum for sarcopenia requires further validation.

Causal association and mediating effect of blood biochemical metabolic traits and brain image-derived endophenotypes on Alzheimer's disease.

Background: Recent genetic evidence supports that circulating biochemical and metabolic traits (BMTs) play a causal role in Alzheimer's disease (AD), which might be mediated by changes in brain structure. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between blood BMTs, brain image-derived phenotypes (IDPs) and AD. Methods: Utilizing the genetic variants associated with 760 blood BMTs and 172 brain IDPs as the exposure and the latest AD summary statistics as the outcome, we analyzed the causal relationship between blood BMTs and brain IDPs and AD by using a two-sample Mendelian randomization (MR) method. Additionally, we used two-step/mediation MR to study the mediating effect of brain IDPs between blood BMTs and AD. Results: Twenty-five traits for genetic evidence supporting a causal association with AD were identified, including 12 blood BMTs and 13 brain IDPs. For BMTs, glutamine consistently reduced the risk of AD in 3 datasets. For IDPs, specific alterations of cortical thickness (atrophy in frontal pole and insular lobe, and incrassation in superior parietal lobe) and subcortical volume (atrophy in hippocampus and its subgroups, left accumbens and left choroid plexus, and expansion in cerebral white matter) are vulnerable to AD. In the two-step/mediation MR analysis, superior parietal lobe, right hippocampal fissure and left accumbens were identified to play a potential mediating role among three blood BMTs and AD. Conclusions: The results obtained in our study suggest that 12 circulating BMTs and 13 brain IDPs play a causal role in AD. Importantly, a subset of BMTs exhibit shared genetic architecture and potentially causal relationships with brain structure, which may contribute to the alteration of brain IDPs in AD.

Discovery and Exploration of Lipid-Modifying Drug Targets for ALS by Mendelian Randomization.

Observational studies have faced challenges in identifying replicable causes for amyotrophic lateral sclerosis (ALS). To address this, we employed an unbiased and data-driven approach to discover and explore potential causal exposures using two-sample Mendelian randomization (MR) analyses. In the phenotype discovery stage, we assessed 3948 environmental exposures from the UK Biobank and utilized ALS summary statistics (Europeans, 20,806 cases, 59,804 controls) as the outcome within a phenome-wide MR pipeline. Through a range of sensitivity analyses, two medication traits were identified to be protective for ALS. In the target exploration stage, we further conducted drug target MR analyses using the latest and trans-ethnic summary data on lipid-related traits and ALS (Europeans, 27,205 cases, 110,881 controls; East Asians, 1234 cases, 2850 controls). Our aim was to explore potential causal drug targets through six lipid-modifying effects. These comprehensive analyses revealed significant findings. Specifically, "cholesterol-lowering medication" and "atorvastatin" survived predefined criteria in the phenotype discovery stage and exhibited a protective effect on ALS. Further in the target exploration stage, we demonstrated that the therapeutic effect of APOB through LDL-lowering was associated with reduced ALS liability in Europeans (OR = 0.835, P = 5.61E - 5). Additionally, the therapeutic effect of APOA1 and LDLR through TC-lowering was associated with reduced ALS liability in East Asians (APOA1, OR = 0.859, P = 5.38E - 4; LDLR, OR = 0.910, P = 2.73E - 5). Overall, we propose potential protective effects of cholesterol-lowering drugs or statins on ALS risk from thousands of exposures. Our research also suggests APOB, APOA1, and LDLR as novel therapeutic targets for ALS and supports their potential protective mechanisms may be mediated by LDL-lowering or TC-lowering effects.

High-Performance enrichment and sensitive analysis of bisphenol and its analogues in water and milk using a novel Ni-Based cationic Metal-Organic framework.

A novel cationic metal-organic framework (iMOF-Ni) was designed and synthesized by a solvothermal method. It was fabricated as a solid-phase extraction (SPE) cartridge and exhibited high adsorption performance for Bisphenols (BPs). The theoretical simulation demonstrated that the adsorption mechanism between iMOF-Ni and BPs was attributed to cation-π bonding, π-π interaction, and electrostatic interactions. Under optimized SPE, a method for analyzing BPs was established by combining high-performance liquid chromatography-diode array detection (HPLC-DAD). The developed method has good linearity (R2 ≥ 0.994), low detection limits (0.07-0.16 ng/mL), and good reproducibility (1.72-6.35 %, n = 6). The applicability of the method was further evaluated by analyzing water and milk samples. Recoveries of four BPs in spiked samples were from 72.2 % to 96.6 %.

Expanding causal genes for Parkinson's disease via multi-omics analysis.

Genome­wide association studies (GWASs) have revealed numerous loci associated with Parkinson's disease (PD). However, some potential causal/risk genes were still not revealed and no etiological therapies are available. To find potential causal genes and explore genetically supported drug targets for PD is urgent. By integrating the expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets from multiple tissues (blood, cerebrospinal fluid (CSF) and brain) and PD GWAS summary statistics, a pipeline combing Mendelian randomization (MR), Steiger filtering analysis, Bayesian colocalization, fine mapping, Protein-protein network and enrichment analysis were applied to identify potential causal genes for PD. As a result, GPNMB displayed a robust causal role for PD at the protein level in the blood, CSF and brain, and transcriptional level in the brain, while the protective role of CD38 (in brain pQTL and eQTL) was also identified. We also found inconsistent roles of DGKQ on PD between protein and mRNA levels. Another 9 proteins (CTSB, ARSA, SEC23IP, CD84, ENTPD1, FCGR2B, BAG3, SNCA, FCGR2A) were associated with the risk for PD based on only a single pQTL after multiple corrections. We also identified some proteins' interactions with known PD causative genes and therapeutic targets. In conclusion, this study suggested GPNMB, CD38, and DGKQ may act in the pathogenesis of PD, but whether the other proteins involved in PD needs more evidence. These findings would help to uncover the genes underlying PD and prioritize targets for future therapeutic interventions.

Observing the effect of physical activity on forward head posture and rounded shoulder posture in young healthy adults.

[Purpose] This study aimed to examine the effects of physical activity on forward head and rounded shoulder postures in healthy young adults. [Participants and Methods] We recruited 20 healthy young adults engaged in high levels of physical activity and 20 healthy young adults engaged in low levels of physical activity. Both groups completed the International Physical Activity Questionnaire (IPAQ) to assess their physical activity levels. The scapular index (SI) was calculated to assess rounded shoulder posture, whereas the craniovertebral angle (CVA) was calculated to assess forward head posture. Differences in SI and CVA between the two groups were examined. [Results] There was a significant difference in the SI between the two groups, with the low physical activity group exhibiting a lower SI than the high physical activity group. However, there was no significant difference in the CVA between the two groups. [Conclusion] Our study showed that low physical activity levels in healthy young adults could negatively affect shoulder posture but not head posture. Therefore, regularly monitoring rounded shoulder posture in individuals with low physical activity levels is recommended for health considerations.

Prevalence and risk factors of difficult mask ventilation: A systematic review and meta-analysis.

STUDY OBJECTIVE: This meta-analysis aimed at identifying the risk factors for and their strengths in predicting difficult mask ventilation (MV) through a systematic approach. DESIGN: Meta-analysis of observational studies. SETTING: Operating room. INTERVENTION: Airway- or patient-related risk factors for difficult MV reported in over 20% of eligible studies identified through literature review. PATIENTS: Adults receiving anesthetic induction with requirement of MV. MEASUREMENTS: Databases including EMBASE, MEDLINE, Google Scholar, and Cochrane Library were searched from inception to July 2022. The primary outcomes were the identification of commonly reported risk factors for MV and a comparison of their strengths in difficult MV prediction, while the secondary outcomes were the prevalence of difficult MV in the general population and those with obesity. MAIN RESULTS: Meta-analysis of 20 observational studies involving 335,846 patients identified 13 risk factors with predictive strengths (all p < 0.05): neck radiation (OR = 5.0, five studies, n = 277,843), increased neck circumference (OR = 4.04, 11 studies, n = 247,871), obstructive sleep apnea (OSA) (OR = 3.61, 12 studies, n = 331,255), presence of beard (OR = 3.35, 12 studies, n = 295,443), snoring (OR = 3.06, 14 studies, n = 296,105), obesity (OR = 2.99, 11 studies, n = 278,297), male gender (OR = 2.76, 16 studies, n = 320,512), Mallampati score III-IV (OR = 2.36, 17 studies, n = 335,016), limited mouth opening (OR = 2.18, six studies, n = 291,795), edentulous (OR = 2.12, 11 studies, n = 249,821), short thyroid-mental distance (OR = 2.12, six studies, n = 328,311), old age (OR = 2, 11 studies, n = 278,750), and limited neck movement (OR = 1.98, nine studies, n = 155,101). The prevalence of difficult MV was 6.1% (16 studies, n = 334,694) and 14.4% (four studies, n = 1152) in the general population and those with obesity, respectively. CONCLUSIONS: Our results demonstrated the strengths of 13 most common risk factors for predicting difficult MV, which may serve as an evidence-based reference for clinicians to incorporate into their daily practice.

Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects. METHODS: A two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated the causal relationship between established AD markers to explore possible mechanisms. Finally, the potential side effects of the druggable genes for AD treatment were assessed using a phenome-wide MR. RESULTS: Overall, 5883 unique druggable genes were aggregated; 33 unique potential druggable genes for AD were identified in at least one dataset (brain or blood), and 5 were validated in a different dataset. Among them, three prior druggable genes (epoxide hydrolase 2 (EPHX2), SERPINB1 and SIGLEC11) reached significant levels in both blood and brain tissues. EPHX2 may mediate the pathogenesis of AD by affecting the entire hippocampal volume. Further phenome-wide MR analysis revealed no potential side effects of treatments targeting EPHX2, SERPINB1 or SIGLEC11. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting the three druggable genes for AD treatment, which will be useful for prioritising AD drug development.

Efficacy and safety of gefapixant for chronic cough: a meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy and safety of gefapixant in adults with chronic cough remain unclear. Our objective was to assess the efficacy and safety of gefapixant using updated evidence. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase databases were searched from inception through September 2022. Subgroup analysis based on dose of gefapixant (i.e. ≤20, 45-50 and ≥100 mg twice daily for low, moderate and high doses, respectively) was performed to explore a potential dose-dependent effect. RESULTS: Five studies involving seven trials showed the efficacy of moderate- or high-dose gefapixant for reducing objective 24-h cough frequency (estimated relative reduction 30.9% and 58.5%, respectively) (i.e. primary outcome) and awake cough frequency (estimated relative reduction 47.3% and 62.8%, respectively). Night-time cough frequency was only reduced with high-dose gefapixant. Consistently, the use of moderate- or high-dose gefapixant significantly alleviated cough severity and improved cough-related quality of life, but increased the risk of all-cause adverse events (AEs), treatment-related AEs and ageusia/dysgeusia/hypogeusia. Subgroup analysis showed dose dependency in both efficacy and AEs with a cut-off dose being ≥45 mg twice daily. CONCLUSIONS: This meta-analysis revealed dose-dependent efficacy and adverse effects of gefapixant against chronic cough. Further studies are required to investigate the feasibility of moderate-dose (i.e. 45-50 mg twice daily) gefapixant in clinical practice.

Association of prognostic nutritional index with risk of contrast induced nephropathy: A meta-analysis.

Background: Although prognostic nutritional index (PNI) has been frequently applied in patients with malignancy or those during postoperative recovery, whether it is also an optimal indicator of the risk of contrast-induced nephropathy (CIN) in patients receiving coronary angiography remains uncertain. This meta-analysis aimed at investigating the clinical association of PNI with the risk of CIN in patients receiving coronary angiography or percutaneous coronary intervention. Methods: Embase, Medline, Cochrane Library, and Google scholar were searched for studies until January 2023. The relationship between CIN risk and PNI (i.e., low vs. high) (primary outcome) as well as other variables (secondary outcomes) were analyzed using a random-effects model. Results: Overall, 10 observational studies with 17,590 patients (pooled incidence of CIN: 18%) were eligible for analysis. There was a higher risk of CIN in patients with a low PNI compared to those with a high PNI [odd ratio (OR) = 3.362, 95% confidence interval (CI): 2.054 to 5.505, p < 0.0001, I 2 = 89.6%, seven studies, 12,972 patients, certainty of evidence: very low]. Consistently, a lower PNI was noted in patients with CIN compared to those without (Mean difference = -5.1, 95% CI: -6.87 to -3.33, p < 0.00001, I 2 = 96%, eight studies, 15,516 patients, certainty of evidence: very low). Other risks of CIN included diabetes and hypertension, while male gender and the use of statins were associated with a lower risk of CIN. Patients with CIN were older, had a higher creatinine level, and received a higher contrast volume compared to those without. On the other hand, pre-procedural albumin, estimated glomerular filtration rate, ejection fraction, hemoglobin, lymphocyte ratio were found to be lower in patients with CIN than in those without. Conclusion: This meta-analysis highlighted an inverse association of PNI with the risk of CIN, which required further studies for verification. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42023389185].

A nomogram to predict the risk of bleeding after discharge from stent-assisted ruptured aneurysm embolization in a Chinese population.

The occurrence of bleeding events after stent-assisted embolization of a ruptured artery requiring continuous double antiplatelet therapy may seriously affect the prognosis of this group of patients. A nomogram can provide a personalized, more accurate risk estimate based on predictors. We, therefore, developed a nomogram to predict the probability of bleeding events in patients with stent-assisted ruptured aneurysm embolization. We performed a single-center retrospective analysis of data collected from patients undergoing stent-assisted ruptured aneurysm embolization between January 2018 and December 2021. Forward stepwise logistic regression was performed to identify independent predictors of adverse events of bleeding after stent-assisted embolization and to establish nomograms. Discrimination and calibration of this model were performed using the area under the ROC curve (AUC-ROC) and the calibration plot. The model is internally validated by using resampling (1000 replicates). A total of 131 patients were identified, and a total of 118 patients met the study criteria. The predictors included in the nomogram were body mass index (BMI), AAi, and MA-ADP. The model showed good resolving power with a ROC area of 0.893 (95% CI: 0.834 ~ 0.952) for this model with good calibration. The nomogram can be used to individualize, visualize, and accurately predict the risk probability of bleeding events after stent-assisted embolization of ruptured aneurysms.

The intriguing roles of Siglec family members in the tumor microenvironment.

Sialic acid-binding receptors are expressed on the surfaces of a variety of immune cells and have complex and diverse immunoregulatory functions in health and diseases. Recent studies have shown that Siglecs could play diverse immune and nonimmune regulatory roles in the tumor microenvironment (TME) and participate in tumor progression through various mechanisms, such as regulating tumor growth and metastasis, mediating the inflammatory response, and promoting tumor immune escape, thereby affecting the prognoses and outcomes of patients. However, depending on the cell type in which they are expressed, each Siglec member binds to corresponding ligands in the microenvironment milieu to drive diverse cell physiological and pathological processes in tumors. Therefore, we herein summarize the expression spectra and functions of the Siglec family in human diseases, particularly cancer, and highlight the possibility of therapeutic interventions targeting the TME in the future.

Extended topological valley-locked surface acoustic waves.

Stable and efficient guided waves are essential for information transmission and processing. Recently, topological valley-contrasting materials in condensed matter systems have been revealed as promising infrastructures for guiding classical waves, for they can provide broadband, non-dispersive and reflection-free electromagnetic/mechanical wave transport with a high degree of freedom. In this work, by designing and manufacturing miniaturized phononic crystals on a semi-infinite substrate, we experimentally realized a valley-locked edge transport for surface acoustic waves (SAWs). Critically, original one-dimensional edge transports could be extended to quasi-two-dimensional ones by doping SAW Dirac "semimetal" layers at the boundaries. We demonstrate that SAWs in the extended topological valley-locked edges are robust against bending and wavelength-scaled defects. Also, this mechanism is configurable and robust depending on the doping, offering various on-chip acoustic manipulation, e.g., SAW routing, focusing, splitting, and converging, all flexible and high-flow. This work may promote future hybrid phononic circuits for acoustic information processing, sensing, and manipulation.

[Acupoint selection for cancer pain: based on current evidence and Delphi method].

Based on literature research and Delphi expert consensus method, the important acupoints for cancer pain was summarized to provide evidence basis for the formulation of Clinical Practice Guide of Acupuncture in the Treatment of Cancer Pain. Through systematic search of Chinese and English databases, 28 clinical studies regarding acupuncture for cancer pain were included. The acupoint selection methods and high-frequency acupoints were summarized and analyzed. Based on this, a Delphi questionnaire was designed and two rounds of questionnaire survey on 30 experts in acupuncture and tumor related fields in China and abroad were conducted. As a result, it was suggested that the individualized acupoint selection should be adopted for acupuncture treatment of cancer pain, with Zusanli (ST 36), Hegu (LI 4), Taichong (LR 3), Sanyinjiao (SP 6), Yanglingquan (GB 34) and ashi points as the main acupoints. Combined with clinical research evidence and expert consensus, the important acupoints for cancer pain were identified. However, clinical acupoint selection still needed further research and refinement.

Blood transfusion practices affect CD4+ CD25+ FOXP3+ regulatory T cells/T helper-17 cells and the clinical outcome of geriatric patients with hip fracture.

Hip fracture (HF) is common among older individuals and associated with high mortality, poor vitality and functional impairment. HF patients suffer whole body immunological changes and that lead to severe consequences, including immobilization, physical impairment and a high risk of complications. The objective of this study was to decipher the pattern of dynamic immunological changes, especially in two major T cell subsets, CD4+ CD25+ FOXP3+ regulatory T (Treg) cells and T helper-17 (Th17) cells, and their balance, during the hospital stay and to observe whether blood transfusion could influence these cells and clinical patietns' prognosis. In this study, ninety-eight consecutive HF patients were initially enrolled, and finally fifty-one patients qualified for the study, and correlation analysis of their clinical parameters was carried out to predict the meaning of their distribution in clinical practice. Our results showed that the frequency of Tregs gradually decreased, while the frequency of Th17 cells slowly increased in HF patients who received blood transfusion. The Treg frequency was inversely correlated with the level of hemoglobin (Hb), and Th17 cell frequency was positively related to fluctuations in Hb levels in HF patients after trauma. HF patients with a better prognosis and survival time showed decreased a Treg frequency and a decreased Treg/Th17 ratio. Transfusion helped reverse the imbalance in the frequencies of Tregs and Th17 cells and the Treg/Th17 ratio and especially contributed to a better outcome in HF patients with moderate-to-severe anemia. In conclusion, a higher frequency of peripheral blood Tregs and a higher Treg/Th17 ratio may be associated with unfavorable outcomes in HF patients, and blood transfusion may benefit moderate-to-severe HF patients rebalance their immune response.

Solidly Mounted Longitudinally Excited Shear Wave Resonator (YBAR) Based on Lithium Niobate Thin-Film.

This paper proposed a solid-mounted (SM) longitudinally excited shear wave resonator (i.e., YBAR). By adopting a 200 nm x-cut LiNbO3 film, top (aluminum) and bottom (platinum) electrodes in 50 nm thickness and 500 nm width, this resonator simultaneously achieves an operating frequency over 5 GHz with an electromechanical coupling coefficient exceeding 50%. Compared with previously proposed YBAR with suspended structure, the proposed SM-YBAR can effectively suppress unwanted spurious modes with only a slight loss of the electromechanical coupling coefficient. The SM-YABR also provides better device stability, possible low-temperature drift coefficient, and a more convenient and mature device processing. It has the potential to meet the multiple requirements for the next generation signal processing devices in terms of high frequency, large bandwidth, stability, and low cost, etc.

Propofol induces apoptosis by activating caspases and the MAPK pathways, and inhibiting the Akt pathway in TM3 mouse Leydig stem/progenitor cells.

Propofol is an anesthetic agent moderating GABA receptors in the nervous system. A number of studies have demonstrated that propofol exerts a negative effect on neural stem cell development in the neonatal mouse hippocampus. However, to the best of our knowledge, there is no study available to date illustrating whether neonatal exposure to propofol affects Leydig stem/progenitor cell development for normal male reproductive development and functions, and the regulatory mechanism remains elusive. In the present study, TM3 cells, a mouse Leydig stem/progenitor cell line, was treated with propofol. The data illustrated that propofol significantly reduced TM3 cell viability. TM3 subG1 phase cell numbers were significantly increased by propofol assayed by flow cytometric analysis. Annexin V/PI double staining assay of the TM3 Leydig cells also demonstrated that propofol increased TM3 cell apoptosis. In addition, cleaved caspase­8, ­9 and ­3 and/or poly(ADP­ribose) polymerase (PARP) were significantly activated by propofol in the TM3 cells. Furthermore, the expression levels of phospho­JNK, phospho­ERK1/2 and phospho­p38 were activated by propofol in the TM3 cells, indicating that propofol induced apoptosis through the mitogen­activated protein kinase (MAPK) pathway. Additionally, propofol diminished the phosphorylation of Akt to increase the apoptosis of TM3 cells. On the whole, the findings of the present study demonstrate that propofol induces TM3 cell apoptosis by activating caspases and MAPK pathways, as well as by inhibiting the Akt pathway in TM3 cells. These findings illustrate that propofol affects the viability of Leydig stem/progenitor cells possibly related to the development of the male reproductive system.