miR-3188 inhibits hepatitis B virus transcription by targeting Bcl-2.

Transcription of the covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is subject to dual regulation by host factors and viral proteins. MicroRNAs (miRNAs) can regulate the expression of target genes at the post-transcriptional level. Systematic investigation of miRNA expression in HBV infection and the interaction between HBV and miRNAs may deepen our understanding of the transcription mechanisms of HBV cccDNA, thereby providing opportunities for intervention. miRNA sequencing and real-time quantitative PCR (qRT-PCR) were used to analyze miRNA expression after HBV infection of cultured cells. Clinical samples were analyzed for miRNAs and HBV transcription-related indicators, using qRT-PCR, enzyme-linked immunoassay (ELISA), and Western blot. miRNA mimics or inhibitors were used to study their effects on the HBV life cycle. The target genes of miR-3188 and their roles in HBV cccDNA transcription were also identified. The expression of 10 miRNAs, including miR-3188, which was significantly decreased after HBV infection, was measured in clinical samples from patients with chronic HBV infection. Overexpression of miR-3188 inhibited HBV transcription, whereas inhibition of miR-3188 expression promoted HBV transcription. Further investigation confirmed that miR-3188 inhibited HBV transcription by targeting Bcl-2. miR-3188 is a key miRNA that regulates HBV transcription by targeting the host protein Bcl-2. This observation provides insights into the regulation of cccDNA transcription and suggests new targets for anti-HBV treatment.

Surufatinib combined with photodynamic therapy induces ferroptosis to inhibit cholangiocarcinoma in vitro and in tumor models.

The curative effect of single therapy for advanced cholangiocarcinoma (CCA) is poor, thus investigating combined treatment strategies holds promise for improving prognosis. Surufatinib (SUR) is a novel multikinase inhibitor that has been confirmed to prolong survival of patients with advanced CCA. Photodynamic therapy (PDT) can also ablate advanced CCA and relieve biliary obstruction. In this study, we explored the anti-CCA effect of SUR combined with PDT, and explored the underlying mechanism. We found that SUR could effectively inhibit the abilities of proliferation, migration and metastasis in CCA cells (HUCCT-1, RBE). The ability of SUR to inhibit CCA was also confirmed by the HUCCT-1 cell xenograft model in Balb/c nude mice and CCA patient-derived organoids. SUR combined with PDT can significantly enhance the inhibitory effect on CCA, and can be alleviated by two ferroptosis inhibitors (Ferrostatin-1, Deferoxamine). By detecting the level of reactive oxygen species, lipid peroxides, malondialdehyde and glutathione, we further confirmed that SUR combined with PDT can inhibit CCA cells by inducing ferroptosis. Glutathione peroxidase 4 (GPX4) belongs to the glutathione peroxidase family and is mainly responsible for the metabolism of intracellular hydrogen peroxide. GPX4 inhibits ferroptosis by reducing cytotoxic lipid peroxides (L-OOH) to the corresponding alcohols (L-OH). Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a member of the long-chain fatty acid coenzyme a synthetase family and is mainly involved in the biosynthesis and catabolism of fatty acids. ACSL4 induces ferroptosis by promoting the accumulation of lipid peroxides. Both SUR and PDT can induce ferroptosis by promoting ACSL4 and inhibiting GPX4. The regulation effect is found to be more significant in combined treatment group. In conclusion, SUR combined with PDT exerted an anti-CCA effect by inducing ferroptosis. Combination therapy provides a new idea for the clinical treatment of CCA.

Three-dimensional gait analysis of orthopaedic common foot and ankle joint diseases.

Walking is an indispensable mode of transportation for human survival. Gait is a characteristic of walking. In the clinic, patients with different diseases exhibit different gait characteristics. Gait analysis describes the specific situation of human gait abnormalities by observing and studying the kinematics and dynamics of limbs and joints during human walking and depicting the corresponding geometric curves and values. In foot and ankle diseases, gait analysis can evaluate the degree and nature of gait abnormalities in patients and provide an important basis for the diagnosis of patients' diseases, the correction of abnormal gait and related treatment methods. This article reviews the relevant literature, expounds on the clinical consensus on gait, and summarizes the gait characteristics of patients with common ankle and foot diseases. Starting from the gait characteristics of individuals with different diseases, we hope to provide support and reference for the diagnosis, treatment and rehabilitation of clinically related diseases.

Dexamethasone attenuates neuropathic pain through spinal microglial expression of dynorphin A via the cAMP/PKA/p38 MAPK/CREB signaling pathway.

This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.

Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

BACKGROUND: Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. METHODS: This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. RESULTS: Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. CONCLUSIONS: Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

Urolithin A Hijacks ERK1/2-ULK1 Cascade to Improve CD8+ T Cell Fitness for Antitumor Immunity.

According to the latest evidence, the microbial metabolite Urolithin A (UA), known for its role in promoting cellular health, modulates CD8+ T cell-mediated antitumor activity. However, the direct target protein of UA and its underlying mechanism remains unclear. Here, this research identifies ERK1/2 as the specific target crucial for UA-mediated CD8+ T cell activation. Even at low doses, UA markedly enhances the persistence and effector functions of primary CD8+ cytotoxic T lymphocytes (CTLs) and human chimeric antigen receptor (CAR) T cells both in vitro and in vivo. Mechanistically, UA interacts directly with ERK1/2 kinases, enhancing their activation and subsequently facilitating T cell activation by engaging ULK1. The UA-ERK1/2-ULK1 axis promotes autophagic flux in CD8+ CTLs, enhancing cellular metabolism and maintaining reactive oxygen species (ROS) levels, as evidenced by increased oxygen consumption and extracellular acidification rates. UA-treated CD8+ CTLs also display elevated ATP levels and enhanced spare respiratory capacity. Overall, UA activates ERK1/2, inducing autophagy and metabolic adaptation, showcasing its potential in tumor immunotherapy and interventions for diseases involving ERKs.

[Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats].

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Quantitative assessments of retinal macular structure among rural-dwelling older adults in China: a population-based, cross-sectional, optical coherence tomography study.

OBJECTIVES: To quantitatively assess and compare retinal macular structures of rural-dwelling older adults in China using two different optical coherence tomography (OCT) scanners and to examine their associations with demographic, lifestyle, clinical and ocular factors. DESIGN, SETTING AND PARTICIPANTS: This population-based, cross-sectional study included 971 participants (age ≥60 years) derived from the Multimodal Interventions to Delay Dementia and Disability in Rural China study. We collected data on demographics, lifestyle factors, clinical conditions (eg, cardiovascular disease (CVD)) and ocular factors (eg, visual acuity and spherical equivalent). We used two models of spectral-domain OCT to measure macular parameters in nine Early Treatment Diabetic Retinopathy Study subfields. Data were analysed using the multiple general linear models. RESULTS: Spectralis OCT demonstrated higher macular thickness but a lower macular volume than Primus 200 OCT (p<0.05). Nasal quadrant of the inner and outer subfields was the thickest, followed by superior quadrant. Adjusting for multiple potential confounding variables, older age was significantly correlated with lower average inner and outer macular thicknesses and overall macular volume. Men had higher macular parameters than women. The presence of CVD was correlated with lower central macular thickness (ß=-6.83; 95% CI: -13.08 to -0.58; p=0.032). Middle school or above was associated with higher average inner macular thickness (ß=7.85; 95% CI: 1.14 to 14.55; p=0.022) and higher spherical equivalent was correlated with lower average inner macular thickness (ß=-1.78; 95% CI: -3.50 to -0.07; p=0.042). CONCLUSIONS: Macular thickness and volume assessed by Spectralis and Primus 200 OCT scanners differ. Older age and female sex are associated with lower macular thickness and volume. Macular parameters are associated with education, CVD and spherical equivalent. TRIAL REGISTERATION NUMBER: MIND-China study (ChiCTR1800017758).

Target Antigens of Membranous Nephropathy With Syphilis Infection.

Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown. Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed. Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection. Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.

Prevalence and associated factors of excessive daytime sleepiness in rural older adults: a population-based study.

OBJECTIVE: To investigate the prevalence and associated factors of excessive daytime sleepiness (EDS) among rural-dwelling Chinese older adults. METHODS: We collected data on demographic, epidemiological, and clinical factors via in-person interviews and clinical examinations following a structured questionnaire. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, the Berlin questionnaire (BQ) to assess obstructive sleep apnea (OSA) risk; and the Epworth Sleepiness Scale (ESS) to assess sleep characteristics. EDS was defined as the total ESS score > 10. RESULTS: This population-based study engaged 4845 participants (age ≥ 65 years, 57.3% female) in the 2018 examination of the Multimodal Interventions to Delay Dementia and Disability in Rural China. The prevalence of EDS was 9.3% in the total sample, 8.3% in females, and 10.6% in males, and the prevalence decreased with advanced age. Logistic regression analysis revealed that EDS was significantly associated with age (multivariable-adjusted odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.95-0.99), female sex (0.53; 0.36-0.77), hypertension (0.68; 0.54-0.85), depressive symptoms (2.68; 2.07-3.46), high OSA risk (2.11; 1.69-2.63), and poor sleep quality (2.12; 1.60-2.82). CONCLUSION: EDS affects nearly one-tenth of rural older adults in China. Older age, female sex, and hypertension were associated with a decreased likelihood of EDS, while depressive symptoms, high OSA risk, and poor sleep quality were correlated with an elevated likelihood of EDS.

Association of Metabolic Syndrome with Macular Thickness and Volume in Older Adults: A Population-Based Optical Coherence Tomography Study.

Background: To explore the associations of the metabolic syndrome (MetS) and individual components with macular thickness and volume among rural-dwelling Chinese older adults. Methods: This population-based cross-sectional study included 705 participants (age ≥60 years) derived from the MIND-China study. In 2018-2019, we collected data through face-to-face interview, clinical examination, optical coherence tomography (OCT) examination, and blood test. We measured macular thickness and volume using spectral-domain OCT. MetS was defined following the International Diabetes Federation (IDF) criteria, the IDF/American Heart Association (AHA) criteria, the National Cholesterol Education Program-Adult Treatment Panel III criteria, and the Chinese Diabetes Society (CDS) criteria. Data were analyzed with multivariable general linear models. Results: MetS was significantly associated with thinner macula in central (multivariable-adjusted ß = -5.29; 95% confidence interval: -9.31 to -1.26), parafoveal (-2.85; -5.73 to 0.04) and perifoveal regions (-4.37; -6.79 to -1.95) when using the IDF criteria, in the perifoveal regions (-3.82; -6.18 to -1.47) when using the IDF/AHA criteria, and in the central region (-5.63; -10.25 to -1.02) when using the CDS criteria, and with reduced macular volume when using the IDF (-0.16; -0.26 to -0.07) and IDF/AHA (-0.13; -0.22 to -0.04) criteria. In the parafoveal region, the IDF-defined MetS was significantly associated with thinner retina in men (ß = -6.25; -10.94 to -1.56) but not in women. Abdominal obesity (-2.83; -5.41 to -0.25) and elevated fasting blood glucose (-2.65; -5.08 to -0.21) were associated with thinner macular thickness in the perifoveal region. Conclusion: MetS is associated with macular thinning and reduced macular volume among rural-dwelling older adults, and the associations vary by the defining criteria of MetS.

Microbiome dysbiosis by antibiotics protects cartilage degradation in OAOP mice.

The role of this study was to evaluate the impact of gut microbiota depletion on the progression of osteoarthritis (OA) and osteoporosis (OP). We conducted an experimental mouse model of OA and OP over an 8-week period. The model involved destabilization of the medial meniscus and bilateral ovariectomy (OVX). To deplete the gut microbiota, we administered a course of antibiotics for 8 weeks. The severity of OA was assessed through micro-CT scanning, X-rays, and immunohistochemical staining. Microbiome analysis was performed using PCR of 16S DNA on fecal samples, and the levels of serum lipopolysaccharide, interleukin 6, tumor necrosis factor-α (TNF-α), osteocalcin, and estrogen were measured using enzyme-linked immunosorbent assay. We found that in comparison to the OVX+OA group, the OVX+OA+ABT group exhibited increased bone mineral density (P < 0.0001), bone volume fraction (P = 0.0051), and trabecular number (P = 0.0023) in the metaphyseal bone. Additionally, cartilage injury and levels of matrix metalloproteinase 13 were reduced in the OVX+OA+ABT group compared to the OVX+OA group. Moreover, the OVX+OA+ABT group demonstrated decreased relative abundance of Bacteroidetes, serum lipopolysaccharide (P = 0.0005), TNF-α (P < 0.0001), CTX-1 (P = 0.0002), and increased expression of bone formation markers. These findings were further supported by correlation network analyses. Depletion of gut microbiota was shown to protect against bone loss and cartilage degradation by modulating the composition of the gut microbiota in osteoporosis and osteoarthritis.

Rice LIKE EARLY STARVATION1 cooperates with FLOURY ENDOSPERM 6 to modulate starch biosynthesis and endosperm development.

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE 1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.

Comparing glycemic traits in defining diabetes among rural Chinese older adults.

BACKGROUND: We sought to identify the optimal cut-off of glycated hemoglobin (HbA1c) for defining diabetes and to assess the agreements of fasting plasma glucose (FPG), fasting serum glucose (FSG), and HbA1c in defining diabetes among rural older adults in China. METHODS: This population-based cross-sectional study included 3547 participants (age ≥61 years, 57.8% women) from the Multidomain Interventions to Delay Dementia and Disability in Rural China from 2018-2019; of these, 3122 had no previously diagnosed diabetes. We identified the optimal cut-off of HbA1c against FPG ≥7.0 mmol/L for defining diabetes by using receiver operating characteristic curve and Youden index. The agreements of FPG, FSG, and HbA1c in defining diabetes were assessed using kappa statistics. RESULTS: Among participants without previously diagnosed diabetes (n = 3122), the optimal HbA1c cut-off for defining diabetes was 6.5% (48 mmol/mol), with the sensitivity of 88.9%, specificity of 93.7%, and Youden index of 0.825. The correlation coefficients were 0.845 between FPG and FSG, 0.574 between FPG and HbA1c, and 0.529 between FSG and HbA1c in the total sample (n = 3547). The kappa statistic for defining diabetes was 0.962 between FSG and FPG, and 0.812 between HbA1c and FPG. CONCLUSIONS: The optimal cut-off of HbA1c for diagnosing diabetes against FPG >7.0 mmol/L is ≥6.5% in Chinese rural-dwelling older adults. The agreement in defining diabetes using FPG, FSG, and HbA1c is nearly perfect. These results have relevant implications for diabetes research and clinical practice among older adults in China. CLINICAL TRIAL REGISTRATION: The protocol of MIND-China was registered in the Chinese Clinical Trial Registry (ChiCTR, www.chictr.org.cn; registration no.: ChiCTR1800017758).

Anatomical Study of Cross-Transfer of the Contralateral C7 Nerve Through the Posterior Epidural Pathway of the Cervical Spine for the Treatment of Spastic Paralysis of the Upper Limbs.

BACKGROUND: This study explored the safety and feasibility of surgical treatment of spastic paralysis of the central upper extremity by contralateral cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine. METHODS: Five fresh head and neck anatomical specimens were employed to simulate contralateral cervical 7 nerve transfer through the posterior epidural pathway of the cervical spine. The relevant anatomical landmarks and surrounding anatomical relationships were observed under a microscope, and the relevant anatomical data were measured and analysed. RESULTS: The posterior cervical incision revealed the cervical 6 and 7 laminae, and lateral exploration revealed the cervical 7 nerve. The length of the cervical 7 nerve outside the intervertebral foramen was measured to be 6.4 ± 0.5 cm. The cervical 6 and cervical 7 laminae were opened with a milling cutter. The cervical 7 nerve was extracted from the inner mouth of the intervertebral foramen, and its length was 7.8 ± 0.3 cm. The shortest distance of the cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine was 3.3 ± 0.3 cm. CONCLUSIONS: Cross-transfer surgery of the contralateral cervical 7 nerve via the posterior epidural pathway of the cervical spine can effectively avoid the risk of nerve and blood vessel damage in anterior cervical nerve 7 transfer surgery; the nerve transfer distance is short, and nerve transplantation is not required. This approach may become a safe and effective procedure for the treatment of central upper limb spastic paralysis.

Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants: A Population-Based Cohort Study.

BACKGROUND: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association. METHODS: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March-September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October-December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3. RESULTS: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (ß coefficient: -0.149, 95% CI: -0.274 to -0.023) and lower long-delayed free recall z score (-0.216, -0.361 to -0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043). CONCLUSIONS: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.

Association of Triglyceride-Glucose Index With Cognitive Function and Brain Atrophy: A Population-Based Study.

OBJECTIVE: To investigate the associations of triglyceride-glucose (TyG) index, a reliable surrogate marker for insulin resistance, with the function of various cognitive domains and brain structures among older adults. DESIGN: A population-based cross-sectional study. SETTING: Older adults living in the rural communities in China. PARTICIPANTS: About 4,541 rural-dwelling dementia-free participants (age ≥65 years; 56.37% women) undertook examinations in March-September 2018 for MIND-China. MEASUREMENTS: TyG index was calculated as ln[fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. A neuropsychological test battery was used to assess memory, attention, verbal fluency, and executive function. Volumetric brain measures were assessed on magnetic resonance imaging (MRI) in a subsample (n = 1,019). Data were analyzed with restricted cubic spline and multivariable general linear models. RESULTS: An inverted J-shaped association was observed between TyG index and z-scores of multiple cognitive domains, such that among individuals with TyG index ≥8.57 (median), a higher TyG index was significantly associated with lower z-scores of memory, attention, verbal fluency, executive function, and global cognition (all p < 0.05); among people with TyG index <8.57, a higher TyG index was significantly associated with a higher executive function z-score (p < 0.05), but not with any of the other examined cognitive domains. In the MRI subsample, a higher TyG index was significantly associated with lower volumes of total brain tissue, gray matter, and white matter as well as greater cerebrospinal fluid volume (p < 0.05), but not with white matter hyperintensity volume. CONCLUSIONS: Insulin resistance, as indicated by a high TyG index, was associated with poor function in multiple cognitive domains and global brain atrophy.

On the Role of Academic Buoyancy and Self-Efficacy in Predicting Teachers' Work Engagement: A Case of Chinese English as a Foreign Language Teachers.

A plethora of scientific evidence has pinpointed that teaching English as a foreign or second language (EFL) is difficult, challenging, and emotionally burdensome. Nevertheless, most English language teachers remain committed to the teaching profession and actively engage in the instructional environment. This has inspired several scholars worldwide to explore what personal, emotional, and psychological factors motivate English language teachers to engage enthusiastically in their workplace. While a large body of studies have to date examined the personal, emotional, and psychological predictors of English language teachers' work engagement, to our knowledge, no inquiry has investigated the role of academic buoyancy and self-efficacy in predicting EFL teachers' work engagement. Furthermore, the potential impact of demographic variables on the interplay between EFL teachers' academic buoyancy, self-efficacy, and work engagement has been disregarded. To bridge this gap, we examined the interplay of these three constructs among Chinese EFL teachers. To do so, we administered three pre-designed questionnaires to 242 EFL teachers working in Chinese schools and universities. The collected data were then analyzed using structural equation modeling (SEM). The outcomes of SEM divulged positive and strong relationships between Chinese EFL teachers' academic buoyancy, self-efficacy, and work engagement. The SEM results also indicated that academic buoyancy and self-efficacy could strongly and favorably predict Chinese EFL teachers' work engagement. Additionally, the study outcomes disclosed that demographic variables, including gender, educational degree, and teaching experience, directly impacted the interplay between Chinese EFL teachers' academic buoyancy, self-efficacy, and work engagement. These results may have significant implications for English teachers, teacher trainers, and educational principals.

Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.

INTRODUCTION: To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. METHODS: This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aß), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS: The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aß and NfL (p < 0.05). DISCUSSION: Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. HIGHLIGHTS: We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.

Non-coding RNAs expression in SARS-CoV-2 infection: pathogenesis, clinical significance, and therapeutic targets.

The coronavirus disease 2019 (COVID-19) pandemic has been looming globally for three years, yet the diagnostic and treatment methods for COVID-19 are still undergoing extensive exploration, which holds paramount importance in mitigating future epidemics. Host non-coding RNAs (ncRNAs) display aberrations in the context of COVID-19. Specifically, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) exhibit a close association with viral infection and disease progression. In this comprehensive review, an overview was presented of the expression profiles of host ncRNAs following SARS-CoV-2 invasion and of the potential functions in COVID-19 development, encompassing viral invasion, replication, immune response, and multiorgan deficits which include respiratory system, cardiac system, central nervous system, peripheral nervous system as well as long COVID. Furthermore, we provide an overview of several promising host ncRNA biomarkers for diverse clinical scenarios related to COVID-19, such as stratification biomarkers, prognostic biomarkers, and predictive biomarkers for treatment response. In addition, we also discuss the therapeutic potential of ncRNAs for COVID-19, presenting ncRNA-based strategies to facilitate the development of novel treatments. Through an in-depth analysis of the interplay between ncRNA and COVID-19 combined with our bioinformatic analysis, we hope to offer valuable insights into the stratification, prognosis, and treatment of COVID-19.