Peripheral blood MR1 tetramer-positive mucosal-associated invariant T-cell function is modulated by mammalian target of rapamycin complex 1 in patients with active tuberculosis.

Tuberculosis (TB) is still an urgent global public health problem. Notably, mucosal-associated invariant T (MAIT) cells play an important role in early anti-TB immune response. Targeted control of them may be an effective method to improve vaccine efficacy and TB treatment. However, the biology and signal regulation mechanisms of MAIT cells in TB patients are still poorly understood. Previous studies have been limited by the lack of reagents to specifically identify MAIT cells. In addition, the use of alternative markers may subsume non-MAIT cell into MAIT cell populations. In this study, the human MR1 tetramer which can specifically identify MAIT cells was used to further explore the effect and mechanism of MAIT cells in anti-TB immune response. Our results showed that the tetramer+ MAIT cells in peripheral blood of TB patients were mainly CD8+ or CD4-CD8- cells, and very few were CD4+ cells. After BCG infecting autologous antigen-presenting cells, MAIT cells in patients produced significantly higher levels of cytokines, lysis and proliferation compared with healthy controls. After suppression of mTORC1 by the mTORC1-specific inhibitor rapamycin, the immune response of MAIT cells in patients was significantly reduced. This study demonstrates that peripheral blood tetramer+ MAIT cells from TB patients have significant anti-TB immune effect, which is regulated by mTORC1. This could provide ideas and potential therapeutic targets for the development of novel anti-TB immunotherapy.

Bongkrekic acid alleviates airway inflammation via breaking the mPTP/mtDAMPs/RAGE feedback loop in a steroid-insensitive asthma model.

Mitochondrial dysfunction is critical in the pathogenesis of asthma. Mitochondrial permeability transition pore (mPTP) regulates the release of mitochondrial damage-associated molecular patterns (mtDAMPs) to maintain mitochondrial homeostasis. Bongkrekic acid (BKA) is a highly selective inhibitor of mPTP opening, participates the progression of various diseases. This research investigated the exact roles of BKA and mPTP in the pathogenesis of asthma and elucidated its underlying mechanisms. In the present study, cytochrome c, one of the mtDAMPs, levels were elevated in asthmatic patients, and associated to airway inflammation and airway obstruction. BKA, the inhibitor of mPTP markedly reversed TDI-induced airway hyperresponsiveness, airway inflammation, and mitochondrial dysfunction. Pretreatment with mitochondrial precipitation, to simulate the release of mtDAMPs, further increased TDI-induced airway inflammation and the expression of RAGE in mice. Administration of the inhibitor of RAGE, FPS-ZM1, alleviated the airway inflammation, the abnormal open of mPTP and mitochondrial dysfunction induced by mtDAMPs and TDI. Furthermore, stimulation with different mtDAMPs activated RAGE signaling in human bronchial epithelial cells. Accordingly, our study indicated that mPTP was important and BKA was efficient in alleviating inflammation in TDI-induced asthma. A positive feedback loop involving mPTP, mtDAMPs and RAGE was present in TDI-induced asthma, indicating that mPTP might serve as a potential therapeutic target for asthma.

Mesenchymal stem cell-derived exosomes ameliorate hypoxic pulmonary hypertension by inhibiting the Hsp90aa1/ERK/pERK pathway.

Hypoxic pulmonary hypertension (HPH) is a serious and life-threatening chronic cardiopulmonary disease characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular remodeling. Mesenchymal stem cell- derived exosomes (MSC-Exos) can relieve HPH by reversing pulmonary vascular remodeling. The HPH model was established in healthy male Sprague-Dawley (SD) rats aged 6 to 8 weeks. The rats were placed in a room with oxygen concentration of (10 ± 1) % for 8 hours a day over 28 days, were then injected intravenously with MSC-Exos (100 ug protein/kg) or equal-volume phosphate buffer saline (PBS) once a day over 1 week. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI) and pulmonary vascular remodeling were observed after anesthesia. In addition, platelet-derived growth factor BB (PDGF-BB) was used to stimulate rat pulmonary artery smooth muscle cells (PASMCs) to construct HPH pathological cell models. The results showed that MSC-Exos could not only reduce the elevation of RVSP, right ventricular hypertrophy and the degree of pulmonary vascular remodeling in HPH rats, but also reduce the proliferation, migration and apoptosis resistance of PASMCs. Finally, GSE53408 and GSE113439 datasets were analyzed and showed that the expression of Hsp90aa1 and pERK/ERK were significantly increased in HPH, also could be inhibited by MSC-Exos. Meanwhile, inhibition of Hsp90aa1 also reduced PASMCs migration and pERK/ERK protein level. In conclusion, MSC-Exos alleviated HPH by suppressing PASMCs proliferation, migration and apoptosis resistance through inhibiting the Hsp90aa1/ERK/pERK pathway.

ERK1/2-CEBPB Axis-Regulated hBD1 Enhances Anti-Tuberculosis Capacity in Alveolar Type II Epithelial Cells.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health crisis with substantial morbidity and mortality rates. Type II alveolar epithelial cells (AEC-II) play a critical role in the pulmonary immune response against Mtb infection by secreting effector molecules such as antimicrobial peptides (AMPs). Here, human ß-defensin 1 (hBD1), an important AMP produced by AEC-II, has been demonstrated to exert potent anti-tuberculosis activity. HBD1 overexpression effectively inhibited Mtb proliferation in AEC-II, while mice lacking hBD1 exhibited susceptibility to Mtb and increased lung tissue inflammation. Mechanistically, in A549 cells infected with Mtb, STAT1 negatively regulated hBD1 transcription, while CEBPB was the primary transcription factor upregulating hBD1 expression. Furthermore, we revealed that the ERK1/2 signaling pathway activated by Mtb infection led to CEBPB phosphorylation and nuclear translocation, which subsequently promoted hBD1 expression. Our findings suggest that the ERK1/2-CEBPB-hBD1 regulatory axis can be a potential therapeutic target for anti-tuberculosis therapy aimed at enhancing the immune response of AEC-II cells.

ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing Prkaa2 mRNA.

Tuberculosis has the highest mortality rate worldwide for a chronic infectious disease caused by a single pathogen. RNA-binding proteins (RBPs) are involved in autophagy - a key defense mechanism against Mycobacterium tuberculosis (M. tuberculosis) infection - by modulating RNA stability and forming intricate regulatory networks. However, the functions of host RBPs during M. tuberculosis infection remain relatively unexplored. Zinc finger NFX1-type containing 1 (ZNFX1), a conserved RBP critically involved in immune deficiency diseases and mycobacterial infections, is significantly upregulated in M. tuberculosis-infected macrophages. Here, we aimed to explore the immunoregulatory functions of ZNFX1 during M. tuberculosis infection. We observed that Znfx1 knockout markedly compromised the multifaceted immune responses mediated by macrophages. This compromise resulted in reduced phagocytosis, suppressed macrophage activation, increased M. tuberculosis burden, progressive lung tissue injury, and chronic inflammation in M. tuberculosis-infected mice. Mechanistic investigations revealed that the absence of ZNFX1 inhibited autophagy, consequently mediating immune suppression. ZNFX1 critically maintained AMPK-regulated autophagic flux by stabilizing protein kinase AMP-activated catalytic subunit alpha 2 mRNA, which encodes a key catalytic α subunit of AMPK, through its zinc finger region. This process contributed to M. tuberculosis growth suppression. These findings reveal a function of ZNFX1 in establishing anti-M. tuberculosis immune responses, enhancing our understanding of the roles of RBPs in tuberculosis immunity and providing a promising approach to bolster antituberculosis immunotherapy.

Exosomes derived from mesenchymal stromal cells exert a therapeutic effect on hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway.

OBJECTIVE: Hypoxic pulmonary hypertension (HPH) is a progressive and life-threatening disease characterized by perivascular inflammation, pulmonary vascular remodeling, and occlusion. Mesenchymal stromal cell-derived exosomes (MSC-exo) have emerged as potential therapeutic agents due to their role in cell communication and the transportation of bioactive molecules. In this study, we aimed to investigate the therapeutic effects of MSC-exo against HPH and elucidate the underlying molecular mechanism. METHODS: Exosomes were isolated from conditioned media of human bone mesenchymal stromal cells using ultracentrifugation and characterized through western blotting, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). An HPH animal model was established in male SD rats, and MSC-exo or phosphate-buffered saline (PBS) were administered via the tail vein for three weeks. Subsequently, right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary vascular remodeling were evaluated. Lung tissues from HPH rats and normal rats underwent high-throughput sequencing and transcriptomic analysis. Gene Ontology (GO) analysis was employed to identify upregulated differentially expressed genes. Additionally, rat pulmonary artery smooth muscle cells (PASMC) exposed to platelet-derived growth factor-BB (PDGF-BB) were used to simulate HPH-related pathological behavior. In vitro cellular models were established to examine the molecular mechanism of MSC-exo in HPH. RESULTS: MSC-exo administration protected rats from hypoxia-induced increases in RVSP, RVHI, and pulmonary vascular remodeling. Additionally, MSC-exo alleviated PDGF-BB-induced proliferation and migration of PASMC. Transcriptomic analysis revealed 267 upregulated genes in lung tissues of HPH rats compared to control rats. Gene Ontology analysis indicated significant differences in pathways associated with Yes Associated Protein 1 (YAP1), a key regulator of cell proliferation and organ size. RT-qPCR and western blot analysis confirmed significantly increased expression of YAP1 in HPH lung tissues and PASMC, which was inhibited by MSC-exo treatment. Furthermore, analysis of datasets demonstrated that Secreted Phosphoprotein 1 (SPP1), also known as Osteopontin (OPN), is a downstream binding protein of YAP1 and can be upregulated by PDGF-BB. MSC-exo treatment reduced the expression of both YAP1 and SPP1. Lentivirus-mediated knockdown of YAP1 inhibited PDGF-BB-induced PASMC proliferation, migration, and SPP1 protein levels. CONCLUSION: Our findings demonstrate that MSC-exo exert a therapeutic effect against hypoxia-induced pulmonary hypertension by modulating the YAP1/SPP1 signaling pathway. The inhibition of YAP1 and downstream SPP1 expression by MSC-exo may contribute to the attenuation of pulmonary vascular remodeling and PASMC proliferation and migration. These results suggest that MSC-exo could serve as a potential therapeutic strategy for the treatment of HPH. Further investigations are warranted to explore the clinical applicability of MSC-exo-based therapies in HPH patients.

Effects of Lactobacillus acidophilus and L. reuteri on bone mass and gut microbiota in ovariectomized mice.

Lactobacillus acidophilus is widely used as a food additive or medication in our daily lives. The objective of this study was to investigate the effects of L. acidophilus and L. reuteri on bone mass in OVX mice and their associated mechanisms. Fifty 6-week-old female C57BL/6J mice were subjected to five different treatments: sham surgery, OVX surgery, OVXandL. reuteri fed, OVXandL. acidophilus fed, OVXandboth L. reuteri and L. acidophilus co-fed, respectively. Serum samples were collected, and IL-1ß,IL-6,TNF-α, and OCN levels were determined. The bone volume fraction and trabecular number, trabecular thickness, trabecular separation, and cortical thickness of the mice were analyzed by micro-CT in both femurs. Mice feces were taken for Illumina high-throughput sequencing to analyze the microbial composition and characteristics. After probiotic feeding, the bone volume fraction, the trabecular number, and the trabecular thickness increased, and the trabecular separation decreased in OVX mice. IL-1ß, IL-6, and TNF-α in the blood significantly decreased. The observed Chao1 and ACE indexes increased significantly. Changes in intestinal microorganisms occurred in all groups of mice. The change of index in the gut microbes, may indicate that the bone mass of OVX mice is changing. L. acidophilus shares the same role as L. reuteri in preventing bone loss in OVX mice. The mechanism of action may be through inhibition of the activation of inflammatory factors in the osteoclast activation pathway in bone metabolism, modulation of gut microbial diversity, and alteration of the richness of specific microorganisms that lead to attenuation of bone loss.

Involvement of 5-HT1A receptors of the thalamic descending pathway in the analgesic effect of intramuscular heating-needle stimulation in a rat model of lumbar disc herniation.

Background: Intramuscular (IM) heating-needle therapy, a non-painful thermal therapy, has been found to exert an analgesic effect via the thalamic ventromedial (VM) nucleus, solely by reducing the triggering threshold for descending inhibition; this could be modulated by intracephalic 5-hydroxytryptamine-1A (5-HT1A) receptors, rather than via the regular analgesia pathway. In this study, the effect and the potential serotonergic mechanism of IM heating-needle stimulation at 43°C were explored in the case of the pathological state of lumbar disc herniation (LDH). Methods: A modified classic rat model of LDH, induced via autologous nucleus pulposus implantation, was utilized. IM inner heating-needles were applied at the attachment point of skeletal muscle on both sides of the L4 and L5 spinous processes. WAY-100635 and 8-OH-DAPT, 5-HT1A receptor antagonist and agonist, were separately injected into the bilateral thalamic mediodorsal (MD) and VM nucleus via an intrathalamic catheter. Nociception was assessed by bilateral paw withdrawal reflexes elicited by noxious mechanical and heat stimulation. Results: IM heating-needle stimulation at a temperature of 43°C for 30 or 45 min significantly relieved both mechanical and heat hyperalgesia in the rat model of LDH (P < 0.05). Heat hyperalgesia was found to be significantly enhanced by administration of WAY-100635 into the thalamic VM nucleus, blocking the effect of heating-needle stimulation in a dose-dependent manner (P < 0.05), while no effects were detected after injection into the thalamic MD nucleus (P > 0.05). Injection of 8-OH-DAPT into the thalamic MD nucleus exerted no modulating effects on either mechanical or heat hyperalgesia (P > 0.05). Conclusion: IM heating-needle stimulation at 43°C for 30 min may activate 5-HT1A mechanisms, via the thalamic VM nucleus, to attenuate hyperalgesia in a rat model of LDH. This innocuous form of thermal stimulation is speculated to selectively activate the descending inhibition mediated by the thalamic VM nucleus, exerting an analgesic effect, without the involvement of descending facilitation of the thalamic MD nucleus.

Cisatracurium besylate rescues Mycobacterium Tuberculosis-infected macrophages from necroptosis and enhances the bactericidal effect of isoniazid.

OBJECTIVE: Tuberculosis is the leading killer among the chronic single-source infectious diseases. Mycobacterium tuberculosis can induce necrotic-dominant multiple modes of cell death in macrophages, which accelerates bacterium dissemination and expands tissue injury in host lungs. Mining drugs to counteract Mycobacterium tuberculosis-induced cell death would be beneficial to tuberculosis patients. METHODS: In this study, the protective drug was screened out from the FDA-approved drug library in Mycobacterium tuberculosis-infected macrophages with CCK-8 assay. The death mode regulated by the drug was identified using transcriptomic sequencing, cytomorphological observation, and in the experimental mouse Mycobacterium tuberculosis-infection model. The functional mechanism was explored using western blot, co-immunoprecipitation, and DARTS assay. The intracellular bacterial survival was detected using colony forming unit assays. RESULTS: Cisatracurium besylate was identified to be highly protective for the viability of macrophages during Mycobacterium tuberculosis infection via inhibiting necroptosis. Cisatracurium besylate prevented RIPK3 to be associated with the executive molecule MLKL for forming the necroptotic complex, resulting in the inhibition of MLKL phosphorylation and pore formation on cell membrane. However, Cisatracurium besylate did not interfere with the association between RIPK3 with its upstream kinase RIPK1 or ZBP1 but regulated RIPK3 autophosphorylation. Moreover, Cisatracurium besylate significantly inhibited the expansion of intracellular Mycobacterium tuberculosis both in vitro and in vivo, which also displayed a strong auxiliary bacteriostatic effect to support the therapeutic efficacy of isoniazid and rifampicin, the first-line anti-tubercular drugs. CONCLUSION: Cisatracurium besylate performs anti-Mycobacterium tuberculosis and anti-necroptotic roles, which potentiates its application to be an adjuvant drug for antituberculosis therapy to assist the battle against drug-resistant tuberculosis.

Viperin deficiency promotes dendritic cell activation and function via NF-kappaB activation during Mycobacterium tuberculosis infection.

OBJECTIVES AND DESIGN: Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. METHODS: We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. RESULTS: Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1ß, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. CONCLUSIONS: These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.

Mediating effect of lower extremity muscle strength on the relationship between mobility and cognitive function in Chinese older adults: A cross-sectional study.

Aging is a multifactorial process associated with irreversible decline in mobility and cognitive function. However, the mechanisms underlying the relationship between mobility and cognitive function remain elusive. In specific, the mediating effect of muscle strength, which is essential to maintain mobility, on this relationship has yet to be clarified. Accordingly, we performed a cross-sectional study involving Chinese older adults to understand the role of muscle strength in the relationship between mobility and cognitive function. The cognitive function and physical performance of 657 community-dwelling participants aged over 65 years old were observed. Cognitive function was assessed using the Mini-Mental State Examination, whereas physical performance, including mobility and muscle strength, was measured via Timed Up-and-Go Test and knee extension strength measurement. Data were statistically analyzed using PROCESS Model 4 developed by Hayes, and 595 complete data were finally included. Physical performance (mobility and muscle strength) was significantly correlated with cognitive function (p < 0.01). Muscle strength was negatively correlated with mobility (r = -0.273, p < 0.001) and positively correlated with cognitive function (r = 0.145, p < 0.001). Muscle strength accounted for 20.1% of the total mediating effects on the relationship between mobility and cognitive function, which revealed the partial mediating role of lower extremity muscle strength in this relationship.

The Role of Acupoint Application of Herbal Medicine for Asthma: Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials.

Background: Acupoint application of herbal medicine (AAHM) has been widely used in China. At present, there is no systematic review of AAHM versus placebo in the treatment of asthma. This systematic review aims to assess the efficacy of AAHM for asthma. Methods: Searches were conducted in five English databases and four Chinese databases from their inceptions until December 2020. Randomized double-blind placebo-controlled trials were screened, and included studies evaluated routine pharmacotherapy (RP) plus AAHM versus RP plus placebo or AAHM versus placebo. The Cochrane risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were performed to evaluate the methodological quality and quality of evidence separately. Results: Sixteen studies involving 1,730 participants were included in this review. Compared with placebo plus RP, participants receiving long-term AAHM plus RP showed improvement in asthma quality of life questionnaire (AQLQ) with moderate-quality evidence (MD 6.53 points, 95% CI 2.70 to 10.36). Low-quality evidence indicated that AAHM plus RP was associated with improved FEV1 (%) compared with placebo plus RP, whether long- or short-term use (MD 11.80%, 95% CI 2.84 to 20.76; MD 10.57%, 95% CI 8.40 to 12.74; respectively). Moderate-quality evidence showed that participants receiving short-term AAHM were associated with a higher AQLQ score (MD 6.57 points, 95% CI 3.76 to 9.38) and a lower frequency of acute exacerbations (MD -1.84, 95% CI -2.32 to -1.36) compared with placebo. Low-quality evidence also indicated that AAHM was associated with improved FEV1 (L) compared with placebo, whether long- or short-term use (MD 0.35 litres, 95% CI 0.03 to 0.67; MD 0.66 litres, 95% CI 0.59 to 0.73; respectively). Conclusions: Moderate-quality evidence is promising that AAHM can improve the quality of life and reduce acute exacerbations in patients with asthma. AAHM also shows a positive role in improving lung function, but the evidence is so indefinite due to low quality.

Association between walking speed and cognitive domain functions in Chinese suburban-dwelling older adults.

Objective: To examine the relationship among walking speed, cognitive impairment, and cognitive domain functions in older men and women living in a Chinese suburban community. Methods: In total, 625 elderly (72.54 ± 5.80 years old) men (n = 258) and women (n = 367) from the Chongming district of Shanghai participated in this study. All participants had Mini-Mental State Examination (MMSE), 4-m walking test, medical history questionnaire, and physical examination. They were grouped according to walking speed (>0.8 vs. ≤ 0.8 m/s) with the stratification of sex. The odds ratio (OR) and the 95% confidence interval (CI) were assessed using the chi-square test and logistic regression analysis. Results: Around 11.6% of men and 14.2% of women had slow walking speeds. After adjusting for age, body mass index (BMI), education level, spouse, faller, the Geriatric Depression Scale (GDS) score, heart disease, stroke, arthritis, and low back pain, walking speed was negatively related to cognitive impairment in men (OR 0.11 [95% CI: 0.01, 0.94]; p = 0.043). In addition, the relationship between walking speed and impaired orientation was significant in both men (OR 0.003 [95% CI: 0.001, 0.05]; p < 0.001) and women (OR 0.15 [95% CI: 0.03, 0.75]; p = 0.021). Conclusion: The relationship between walking speed and cognitive impairment was only significant in men, but the association with impaired orientation was found in both men and women. Assessing the walking speed of the elderly is beneficial, which may help with early detection and early therapeutic prevention of cognitive impairment.

Modulation of Brain Activity and Functional Connectivity by Acupuncture Combined With Donepezil on Mild-to-Moderate Alzheimer's Disease: A Neuroimaging Pilot Study.

Background: Functional brain imaging changes have been proven as potential pathophysiological targets in early-stage AD. Current longitudinal neuroimaging studies of AD treated by acupuncture, which is one of the growingly acknowledged non-pharmacological interventions, have neither adopted comprehensive acupuncture protocols, nor explored the changes after a complete treatment duration. Thus, the mechanisms of acupuncture effects remain not fully investigated. Objective: This study aimed to investigate the changes in spontaneous brain activity and functional connectivity and provide evidence for central mechanism of a 12-week acupuncture program on mild-to-moderate AD. Methods: A total of forty-four patients with mild-to-moderate AD and twenty-two age- and education-level-matched healthy subjects were enrolled in this study. The forty-four patients with AD received a 12-week intervention of either acupuncture combined with Donepezil (the treatment group) or Donepezil alone (the control group). The two groups received two functional magnetic resonance imaging (fMRI) scans before and after treatment. The healthy subject group underwent no intervention, and only one fMRI scan was performed after enrollment. The fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were applied to analyze the imaging data. The correlations between the imaging indicators and the changed score of Alzheimer's Disease Assessment Scale-Cognitive Section (ADAS-cog) were also explored. Results: After the 12-week intervention, compared to those in the control group, patients with AD in the treatment group scored significantly lower on ADAS-cog value. Moreover, compared to healthy subjects, the areas where the fALFF value decreased in patients with AD were mainly located in the right inferior temporal gyrus, middle/inferior frontal gyrus, middle occipital gyrus, left precuneus, and bilateral superior temporal gyrus. Compared with the control group, the right precuneus demonstrated the greatest changed value of fALFF after the intervention in the treatment group. The difference in ADAS-cog after interventions was positively correlated with the difference in fALFF value in the left temporal lobe. Right precuneus-based FC analysis showed that the altered FC by the treatment group compared to the control group was mainly located in the bilateral middle temporal gyrus. Conclusion: The study revealed the key role of precuneus in the effect of the combination of acupuncture and Donepezil on mild-to-moderate AD for cognitive function, as well as its connection with middle temporal gyrus, which provided a potential treating target for AD. Trial Registration Number: NCT03810794 (http://www.clinicaltrials.gov).

3D-Printed Bionic Titanium Alloy Artificial Lamina Prevents Epidural Adhesion and Restores the Stability After Laminectomy in Pigs.

Laminectomy can cause the dura mater to adhere to the surrounding scar tissue, leading to soft spinal stenosis after surgery. Although artificial laminae are considered ideal substitutes, they present challenges such as insecure fixation and insufficient bionics. In this study, we fabricated a bionic titanium alloy artificial lamina using three-dimensional (3D)-printing technology and evaluated its adhesion prevention and stability after laminectomy in pigs. An in vitro biomechanical pull-out resistance test indicated that the pull-out strength of the artificial lamina was close to that of a single pedicle screw and was significantly higher than that of a cortical screw. In vivo animal implantation results indicated precise laminectomy and artificial lamina implantation, as well as a safe operation process with the assistance of guide plates. X-ray and computed tomography results indicated the well fixation of bionic titanium alloy artificial lamina and screws 10 weeks after laminectomy. The artificial lamina was not loosened after being removed from pigs (postoperative week 12), exhibiting good stability. Additionally, no adhesion was observed in the artificial lamina group, whereas a large amount of scar tissue in the spinal canal covered the dural surface in the control group. Thus, 3D-printed bionic titanium alloy artificial lamina can prevent epidural adhesion after laminectomy, while restoring the structural stability of the posterior complex, suggesting the potential of lamina substitutes for adhesion prevention after laminectomy.

Mobility speed predicts new-onset hypertension: a longitudinal study.

OBJECTIVE: The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals. METHODS: This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension. RESULTS: In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10-1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01-0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99-1.06; P = 0.098) was not significantly associated with hypertension incidence. CONCLUSION: Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.

Psychometric properties of the Chinese version of the Courtauld Emotional Control Scale in women newly diagnosed with breast cancer.

PURPOSE: Emotional control, the attempt to suppress the expression of negative effects, is an essential factor in the prevalence of psychological distress in women with breast cancer. The Courtauld Emotional Control Scale (CECS) is a commonly used self-report tool for assessing emotional suppression in both clinical and general groups. This study aimed to validate the Chinese version of the Courtauld Emotional Control Scale (CECS) in women newly diagnosed with breast cancer. METHODS: The study involved 680 women newly diagnosed with breast cancer aged 25 to 76 (mean age = 48.19, standard deviation (SD) = 8.57) from Changsha (China). Data analysis included Cronbach's alpha coefficients, the intraclass correlation coefficient (ICC), Pearson's correlations, Independent-Samples T test, confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) were conducted to determine the optimal model. For the best fitting model stability was assessed with tests for invariance across age, educational level, and employment status. RESULTS: Internal consistency (α = 0.987) and test-retest reliability (ICC = 0.715) of the CECS were presented. Results confirm the structure of the Chinese version of the CECS with 21 items divided into three dimensions, anger suppression (CECS_AG), depression suppression (CECS_MD), and anxiety suppression (CECS_AX). Convergent and known-groups validity were acceptable. Additionally, this model remained invariant across age, educational levels, and employment status. CONCLUSIONS: The Chinese version of the CECS has good psychometric properties in terms of reliability and validity, remaining invariant across age, educational levels, and employment status in women newly diagnosed with breast cancer.

Chinese patent medicine for functional dyspepsia effects: A protocol for systematic review and Bayesian network meta-analysis.

BACKGROUND: In recent years, many clinical studies have suggested that various Chinese patent medicines have the potential to treat functional dyspepsia (FD). This study aims to conduct a systematic review and Bayesian network meta-analysis to evaluate the effectiveness of different Chinese patent medicines for FD. METHODS: A comprehensive retrieval method will be executed in the following databases: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), VIP Database, and Wanfang Database. Clinical randomized controlled trials (RCTs) of 9 Chinese patent medicines for FD are searched, and the retrieval time is from inception to October 2021. Three reviewers will screen the RCTs that meet the inclusion criteria and extract the data independently. The outcomes include total clinical efficiency, cure rate, recurrence rate, symptom score, and adverse events. Cochrane risk-of-bias tool will be carried to assess RCTs quality. The "gemtc" package and "rjags" package in R software will be used to manage data within the Bayesian framework. RESULTS: The results can provide relatively objective evidence to evaluate the effectiveness of these 9 Chinese patent medicines in treating FD, which may help clinicians to develop a more effective and safer treatment plan. CONCLUSION: This study aims to provide new options for Chinese patent medicine treatment of FD in terms of its efficacy and safety.

Long Sleep Duration Associated With Cognitive Impairment in Chinese Community-Dwelling Older Adults.

ABSTRACT: We aimed to examine the association between sleep duration and impaired cognitive function in different cognitive domains in Chinese community-dwelling older adults. A total of 1591 participants (≥60 years) were divided into five groups: ≤6 hours (very short sleep duration), >6 to 7 hours (short sleep duration), ≥7 to 8 hours (moderate sleep duration), >8 to 9 hours (moderately long sleep duration), and >9 hours (long sleep duration), according to sleep duration. Cognitive function was assessed using the Mini-Mental State Examination. Long sleep duration significantly increased the likelihood of cognitive impairment. In addition to attention, long sleep duration was negatively related to poorer global cognition and other cognitive domain functions. With the stratification of age groups, long sleep duration was negatively associated with other cognitive domain functions except delayed recall in older elderly (≥75 years) people, but not in younger elderly (60-74 years) people. Long sleep duration was associated with higher rates of cognitive impairment, poorer global cognition, and declined orientation, memory, language ability, and executive function in Chinese community-dwelling older adults, which was more significant in older elderly people.