In-hospital complications and readmission patterns in 13,937 patients with developmental dysplasia of the hip undergoing total hip arthroplasty: Evidence from the Chinese national database.

PURPOSE: Clarifying the prognosis and readmission patterns of patients with developmental dysplasia of the hip (DDH) following total hip arthroplasty (THA) would provide important references for clinical management for this population. Using the Chinese national inpatient database (i.e., Hospital Quality Monitoring System [HQMS]), we aimed to compare in-hospital complications and readmission patterns following THA in patients with DDH and primary osteoarthritis (OA). METHODS: Patients undergoing THA for DDH and OA between 2013 and 2019 were identified using the HQMS. Demographics and clinical characteristics were compared between the two groups. After propensity score matching, in-hospital complications and readmission patterns were compared using a logistic regression model. RESULTS: According to the analysis of 13,937 propensity-score matched pairs, there were no significant differences in the incidence of in-hospital death (0.01 % vs 0.04 %, P = 0.142), transfusion (8.09 % vs 7.89 %, P = 0.536), wound infection (0.31 % vs 0.25 %, P = 0.364), deep venous thrombosis (0.45 % vs 0.43 %, P = 0.786), pulmonary embolism (0.03 % vs 0.05 %, P = 0.372) or all-cause readmission (2.87 % vs 3.12 %, P = 0.219) between two groups. However, DDH patients had higher surgical readmission rates than OA patients (1.43 % vs 1.14 %, P = 0.033). When analyzing causes of surgical readmission, DDH patients had increased risk of dislocation (0.37 % vs 0.21 %, P = 0.011) and aseptic loosening (0.17 % vs 0.07 %, P = 0.024) than OA patients. CONCLUSION: DDH patients had an increased risk of surgical readmission following THA, mainly driven by dislocation and aseptic loosening, which should be recognized and appropriately prevented.

Trends, complications, and readmission of allogeneic red blood cell transfusion in primary total hip arthroplasty in china: a national retrospective cohort study.

INTRODUCTION: Decrease in allogenic red blood cell (RBC) transfusion rates following total hip arthroplasty (THA) has been reported in the United States, but whether other countries share the same trend remains unclear. Additionally, the relation of allogenic RBC transfusion to the risk of complications in THA remains controversial. Using the Chinese national inpatient database, the current study aimed to examine trends, complications, charges, and readmission patterns of allogeneic RBC transfusion in THA. MATERIALS AND METHODS: Patients undergoing primary THA between 2013 and 2019 were included, and then stratified into the transfusion and the non-transfusion group based on the database transfusion records. A generalized estimating equation model was used to investigate trends in transfusion rates. After propensity-score matching, a logistic regression model was used to compare the complications, rates and causes of 30-day readmission between two groups. RESULTS: A total of 10,270 patients with transfusion and 123,476 patients without transfusion were included. Transfusion rates decreased from 19.11% in 2013 to 9.94% in 2019 (P for trend < 0.001). After matching, no significant differences in the risk of of in-hospital death (odds ratio [OR], 4.00; 95% confidence interval [CI] 0.85-18.83), wound infection (OR 0.72; 95%CI 0.45-1.17), myocardial infarction (OR 1.17; 95%CI 0.62-2.19), deep vein thrombosis (OR 1.25; 95%CI 0.88-1.78), pulmonary embolism (OR 2.25; 95%CI 0.98-5.17), readmission rates (OR 1.07; 95%CI 0.88-1.30) and readmission causes were observed between two groups. However, the transfusion group had higher hospitalization charges than the non-transfusion group (72,239.89 vs 65,649.57 Chinese yuan [CNY], P < 0.001). CONCLUSIONS: This study found that allogeneic RBC transfusion in THA was not associated with the increased risk of complications and any-cause readmission. However, the currently restrictive transfusion policy should be continued because excessive blood transfusion may increase the socioeconomic burden.

Relevant detection indicator of prethrombotic state in patients with primary hypertension.

BACKGROUND: Hypertension is a common chronic disease that affects many people worldwide. Only a few reports related to the exploration of relevant indicators of the prethrombotic state in patients with primary hypertension (PH) in clinical settings were available. AIM: To detect prethrombotic state-related indicators in patients with PH and analyze their differences in different patient populations to provide a laboratory basis for the clinical prevention and control of hypertensive thrombotic diseases. METHODS: The general data of patients with PH who attended the Department of Cardiovascular Medicine, The First Affiliated Hospital of Jiangxi Medical College, from January 2022 to December 2022 were collected retrospectively. The patients were divided into three groups of 40 patients each according to the Grade of PH: Grade 1, Grade 2, and Grade 3 hypertension experimental group. The baseline data of 40 volunteers, who underwent physical examination in our hospital but were not diagnosed with PH during the same period, were included in the control group. The relevant indicators of prethrombotic state of the participants were compared, and mainly included inflammation-related indicators, hemorheology-related indicators, and coagulation function related indicators. The relationship between the aforementioned indicators and the progression of PH was analyzed. RESULTS: No significant differences were observed in age, sex, diabetes mellitus, smoking history, drinking history, body mass index, New York Heart Association functional classification, or the course of hypertension among the four groups (P > 0.05). The expressions of high-sensitivity C-reactive protein (hs-CRP), thrombomodulin (TM), hematocrit (Hct), erythrocyte sedimentation rate (ESR), P-selectin on platelet surface (CD62P), and fibrinogen (FIB) in the control group were < Grade 1 hypertension group < Grade 2 hypertension group < Grade 3 hypertension group, and the expressions of platelet (PLT), activated partial thromboplastin time (APTT), prothrombin (PT), and plasma thrombin time (TT) in the control group was > Grade 1 hypertension group > Grade 2 hypertension group > Grade 3 hypertension group, and the difference was statistically significant (P < 0.05). The results of the multivariate logistic regression model showed that the expression of hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB in the included participants was related to the progression of PH. Among these, high expression of hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT, and low expression of PLT and FIB were risk factors for PH (OR > 1, P < 0.05). The results of the receiver operating characteristic curve analysis showed that the area under the curve of hs-CRP, TM, ESR, CD62P, APTT, PT, TT, and FIB for the prediction of PH were > 0.80, and the prediction value was ideal. Linear correlation analysis with bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT were positively correlated with each other (r > 0, P < 0.05); PLT and FIB were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, APTT, PT, and TT (r < 0, P < 0.05); and PLT and FIB were positively correlated (r > 0, P < 0.05). Linear correlation analysis using bivariate Spearman showed that hs-CRP, TM, Hct, ESR, CD62P, and FIB were positively correlated with each other (r > 0, P < 0.05), whereas PLT, APTT, PT, and TT were negatively correlated with hs-CRP, TM, Hct, ESR, CD62P, and FIB (r < 0, P < 0.05). There was a positive correlation between PLT, APTT, PT, and TT (r > 0, P < 0.05). CONCLUSION: The relevant indicators of the prethrombotic state in patients with PH, such as hs-CRP, TM, Hct, ESR, CD62P, PLT, APTT, PT, TT, and FIB, showed differences. High expression of hs-CRP, TM, Hct, ESR, CD62P, and FIB, and low expression of PLT, APTT, PT, and TT are the keys to the occurrence, progression, and thrombotic state of PH. Based on the above serum indicators' expression in patients, targeted interventions can be administered to patients with abnormal expression levels to control the progression of their disease and reduce the risk of developing a prethrombotic state.

Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke.

BACKGROUND: Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined. METHODS: We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3-5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry. RESULTS: STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice. CONCLUSIONS: Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.

The association of melatonin use and hip fracture: a matched cohort study.

By using propensity-score matched cohorts, we compared the risk of incident hip fracture between melatonin initiators and hypnotic benzodiazepines initiators. The initiation of melatonin was not associated with an increased risk of hip fracture. INTRODUCTION: Melatonin is hypothesized to suppress bone loss, but a previous study reported an increased risk of hip fracture among melatonin users compared with non-users, which was however susceptible to confounding by indication. This study aimed to compare the risk of hip fracture between melatonin initiators and initiators of its active comparators, i.e., hypnotic benzodiazepines. METHODS: Among individuals aged 40 years or older without a history of hip fracture or cancer in the IQVIA Medical Research Database (IMRD) in the UK (2000-2018), a propensity score-matched cohort study was conducted to examine the association of melatonin initiation vs. hypnotic benzodiazepines initiation with the risk of hip fracture. RESULTS: After propensity score matching, 9,038 patients were included (4,519 melatonin initiators and 4,519 hypnotic benzodiazepines initiators). During the entire follow-up, 41 cases of hip fracture occurred in the melatonin cohort, and 51 cases occurred in the hypnotic benzodiazepines cohort. The absolute rate difference in hip fracture between melatonin initiators and hypnotic benzodiazepines initiators was -0.8 (95% CI: -1.9 to 0.3) per 1000 person-years and the multivariable-adjusted hazard ratio (HR) of hip fracture for melatonin initiators was 0.78 (95% CI: 0.51 to 1.17). CONCLUSION: In this population-based cohort study, the risk of hip fracture among melatonin initiators was not higher, if not lower, than that among hypnotic benzodiazepines initiators.

Burden and Characteristics of Revision Total Knee Arthroplasty in China: A National Study Based on Hospitalized Cases.

BACKGROUND: National epidemiological data in China are absent for revision total knee arthroplasty (TKA). This study aimed to investigate the burden and characteristics of revision TKA in China. METHODS: We reviewed 4,503 revision TKA cases registered in the Hospital Quality Monitoring System in China between 2013 and 2018 using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Revision burden was determined by the ratio of the number of revision procedures to the total number of TKA procedures. Demographic characteristics, hospital characteristics, and hospitalization charges were identified. RESULTS: The revision TKA cases accounted for 2.4% of all TKA cases. The revision burden showed an increasing trend from 2013 to 2018 (2.3% to 2.5%) (P for trend = .034). Gradual increases in revision TKA were observed in patients aged > 60 years. The most common causes for revision TKA were infection (33.0%) and mechanical failure (19.5%). More than 70% of the patients were hospitalized in provincial hospitals. A total of 17.6% patients were hospitalized in a hospital outside the province of their residence. The hospitalization charges continued to increase between 2013 and 2015 and remained roughly stable over the next three years. CONCLUSIONS: This study provided epidemiological data for revision TKA in China based on a national database. There was a growing trend of revision burden during the study period. The focalized nature of operations in a few higher volume regions was observed and many patients had to travel to obtain their revision procedure.

Diagnostic and therapeutic strategies of acute invasive fungal rhinosinusitis.

Acute invasive fungal rhinosinusitis (AIFR) is a rare disease, but the prognosis is by no means ideal. Pathologically, fungal infection is not only located in the sinus cavity, but also invades the sinus mucosa and bone wall, the surrounding structures and tissues such as the orbit and anterior skull base are often compromised and are accompanied with intracranial and extracranial complications. Despite decades of efforts, acute invasive fungal rhinosinusitis remains a devastating disease, the mortality of the disease continues to hover around 50%. The main impediments to improving the prognosis of acute invasive fungal rhinosinusitis are the difficulties of early diagnosis and the rapid reversal of immune insufficiency. Moreover, aggressive surgery combined with systemic antifungal therapy are significant positive prognostic factors as well. Progress and standardization of AIFR treatment protocols have been limited by the scarcity of the disease and the absence of published randomized studies. Therewith, how to improve the therapeutic outcome and reduce the mortality rate has always been a challenging clinical discussion. We have summarized the relevant case series and literature from the recent years, management with optimal diagnostic and curative strategies are reviewed.

TMEM16F may be a new therapeutic target for Alzheimer's disease.

TMEM16F is involved in many physiological processes such as blood coagulation, cell membrane fusion and bone mineralization. Activation of TMEM16F has been studied in various central nervous system diseases. High TMEM16F level has been also found to participate in microglial phagocytosis and transformation. Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer's disease. However, few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer's disease. In this study, we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD. We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome. Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice. After TMEM16F knockdown in mice, spatial memory ability was improved, microglia polarization to the M2 phenotype was promoted, NLRP3 inflammasome activation was inhibited, cell apoptosis and Aß plaque deposition in brain tissue were reduced, and brain injury was alleviated. We used amyloid-beta (Aß25-35) to stimulate human microglia to construct microglia models of Alzheimer's disease. The levels of TMEM16F, inducible nitric oxide synthase (iNOS), proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aß25-35 treated group compared with that in the control group. TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3, reduced the release of proinflammatory factors interleukin-1, interleukin-6 and tumor necrosis factor-α, and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1ß and interleukin-18. This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin. Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer's disease through participating in polarization of microglia and activation of the NLRP3 inflammasome. These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer's disease treatment.

Untying the Gordian knot of plastid phylogenomic conflict: A case from ferns.

Phylogenomic studies based on plastid genome have resolved recalcitrant relationships among various plants, yet the phylogeny of Dennstaedtiaceae at the level of family and genera remains unresolved due to conflicting plastid genes, limited molecular data and incomplete taxon sampling of previous studies. The present study generated 30 new plastid genomes of Dennstaedtiaceae (9 genera, 29 species), which were combined with 42 publicly available plastid genomes (including 24 families, 27 genera, 42 species) to explore the evolution of Dennstaedtiaceae. In order to minimize the impact of systematic errors on the resolution of phylogenetic inference, we applied six strategies to generate 30 datasets based on CDS, intergenic spacers, and whole plastome, and two tree inference methods (maximum-likelihood, ML; and multispecies coalescent, MSC) to comprehensively analyze the plastome-scale data. Besides, the phylogenetic signal among all loci was quantified for controversial nodes using ML framework, and different topologies hypotheses among all datasets were tested. The species trees based on different datasets and methods revealed obvious conflicts at the base of the polypody ferns. The topology of the "CDS-codon-align-rm3" (CDS with the removal of the third codon) matrix was selected as the primary reference or summary tree. The final phylogenetic tree supported Dennstaedtiaceae as the sister group to eupolypods, and Dennstaedtioideae was divided into four clades with full support. This robust reconstructed phylogenetic backbone establishes a framework for future studies on Dennstaedtiaceae classification, evolution and diversification. The present study suggests considering plastid phylogenomic conflict when using plastid genomes. From our results, reducing saturated genes or sites can effectively mitigate tree conflicts for distantly related taxa. Moreover, phylogenetic trees based on amino acid sequences can be used as a comparison to verify the confidence of nucleotide-based trees.

Neuroprotection against ischemic stroke requires a specific class of early responder T cells in mice.

Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor-like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation.

Population-based metagenomics analysis reveals altered gut microbiome in sarcopenia: data from the Xiangya Sarcopenia Study.

BACKGROUND: Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia. METHODS: Participants were from a community-based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi-frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5-time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota-based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver-operating characteristic curve (AUC). RESULTS: The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). ß-diversity indicated by Bray-Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α-diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P < 0.001, Q = 0.035), Hungatella effluvii (P = 0.003, Q = 0.090), Bacteroides fluxus (P = 0.002, Q = 0.089), Absiella innocuum (P = 0.002, Q = 0.072), Coprobacter secundus (P = 0.002, Q = 0.085) and Clostridium citroniae (P = 0.001, Q = 0.060) than those without sarcopenia. The relative abundance of six species (Desulfovibrio piger, Clostridium symbiosum, Hungatella effluvii, Bacteroides fluxus, Absiella innocuum, and Clostridium citroniae) was also positively associated with sarcopenia severity. A differential species-based model was constructed to separate participants with sarcopenia from controls. The value of the AUC was 0.852, suggesting that model has a decent discriminative performance. Desulfovibrio piger ranked the highest in this model. Functional annotation analysis revealed that the phenylalanine, tyrosine, and tryptophan biosynthesis were depleted (P = 0.006, Q = 0.071), while alpha-Linolenic acid metabolism (P = 0.008, Q = 0.094), furfural degradation (P = 0.001, Q = 0.029) and staurosporine biosynthesis (P = 0.006, Q = 0.072) were enriched in participants with sarcopenia. Desulfovibrio piger was significantly associated with staurosporine biosynthesis (P < 0.001). CONCLUSIONS: This large population-based observational study provided empirical evidence that alterations in the gut microbiome composition and function were observed among individuals with sarcopenia.

[Clinical application of LASEREO endoscopic system in early gastric cancer].

Objective: To evaluate the clinical application of LASEREO endoscopic system in early gastric cancer (EGC). Methods: A total of 68 patients diagnosed with EGC were retrospectively analyzed between August 2017 to December 2020 in Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine. There were 50 males and 18 females finally enrolled with a median age of 64 years. EGCs were analyzed from subjective and objective aspect, as well as from magnification and non-magnification status. Six endoscopists evaluated the visibility of the EGC (RSC) and calculated the color difference (ΔEC) between EGC and the surrounding mucosa in white light imaging (WLI), blue light imaging-bright (BLI-Bri) and linked color imaging (LCI) modes. In the case of magnification (×80), the visibility of the microstructures and microvessels (RSV) was analyzed and the color difference (ΔEV) between microvessels and non-vessels areas were calculated in WLI, BLI and LCI modes. The visibility was evaluated using visibility ranking scale(RS) and the color difference (ΔE) was calculated using L*a*b* color space. Results: In WLI, BLI-Bri, and LCI modes, the mean (±SD) RSC were 2.56±0.68, 2.63±0.59 and 3.17±0.50, and the mean(±SD) ΔEC were 15.71±5.58, 12.04±3.73, and 22.84±8.46, respectively, which in LCI were higher than those in WLI and BLI-Bri modes (P<0.001).Regarding the data evaluated by senior endoscopists, the RSC was higher in BLI-Bri than that in WLI mode (2.98±0.58 vs. 2.79±0.73, P<0.001), but as to those evaluated by junior endoscopists, there were no significant differences between the WLI and BLI-Bri modes(2.29±0.72 vs. 2.23±0.72,P =0.218).In magnifying endoscopy with WLI, BLI, and LCI modes, the mean(±SD) RSV were 2.95±0.28, 3.46±0.40, and 3.38±0.33, and the mean (±SD) ΔEV were 21.68±7.52, 44.29±10.94, and 45.38±14.29, respectively.The RSV and ΔEV in LCI and BLI were higher than that in WLI mode (P<0.001). Conclusions: LCI improves the visibility of EGC by increasing ΔEC, especially in junior endoscopists. Both BLI and LCI improve the visibility of microstructures and microvessels under magnification.

Brachial plexus bridging with specific extracellular matrix-modified chitosan/silk scaffold: a new expand of tissue engineered nerve graft.

Objective.Brachial plexus injuries (BPIs) result in serious dysfunction, especially brachial plexus defects which are currently treated using autologous nerve graft (autograft) transplantation. With the development of tissue engineering, tissue engineered nerve grafts (TENGs) have emerged as promising alternatives to autografts but have not yet been widely applied to the treatment of BPIs. Herein, we developed a TENG modified with extracellular matrix generated by skin-derived precursor Schwann cells (SKP-SCs) and expand its application in upper brachial plexus defects in rats.Approach.SKP-SCs were co-cultured with chitosan neural conduits or silk fibres and subjected to decellularization treatment. Ten bundles of silk fibres (five fibres per bundle) were placed into a conduit to obtain the TENG, which was used to bridge an 8 mm gap in the upper brachial plexus. The efficacy of this treatment was examined for TENG-, autograft- and scaffold-treated groups at several times after surgery using immunochemical staining, behavioural tests, electrophysiological measurements, and electron microscopy.Main results.Histological analysis conducted two weeks after surgery showed that compared to scaffold bridging, TENG treatment enhanced the growth of regenerating axons. Behavioural tests conducted four weeks after surgery showed that TENG-treated rats performed similarly to autograft-treated ones, with a significant improvement observed in both cases compared with the scaffold treatment group. Electrophysiological and retrograde tracing characterizations revealed that the target muscles were reinnervated in both TENG and autograft groups, while transmission electron microscopy and immunohistochemical staining showed the occurrence of the superior myelination of regenerated axons in these groups.Significance.Treatment with the developed TENG allows the effective bridging of proximal nerve defects in the upper extremities, and the obtained results provide a theoretical basis for clinical transformation to expand the application scope of TENGs.

A long noncoding RNA functions in high-light-induced anthocyanin accumulation in apple by activating ethylene synthesis.

Anthocyanin production in apple (Malus domestica) fruit and their consequent coloration can be induced by high-light treatment. The hormone ethylene is also essential for this coloration, but the regulatory relationships that link ethylene and light with anthocyanin-associated coloration are not well defined. In this study, we observed that high-light treatment of apple fruit increased anthocyanin accumulation more than moderate-light treatment did and was the main contributor of induced ethylene production and activation of anthocyanin biosynthesis. A transcriptome study of light-treated apple fruit suggested that a long noncoding RNA (lncRNA), MdLNC610, the corresponding gene of which is physically located downstream from the 1-aminocyclopropane-1-carboxylate oxygenase (ACO) ethylene biosynthesis gene MdACO1, likely affects anthocyanin biosynthesis under high-light treatment. Expression and promoter ß-glucuronidase reporter analyses further showed that MdLNC610 upregulates expression of MdACO1 and so likely participates in high-light-induced ethylene biosynthesis. Overexpression of MdACO1 and MdLNC610 in apple fruit and calli indicated that a major increase in MdLNC610 expression activates MdACO1 expression, thereby causing an increase in ethylene production and anthocyanin levels. These results suggest that MdLNC610 participates in the regulation of high-light-induced anthocyanin production by functioning as a positive regulator to promote MdACO1 expression and ethylene biosynthesis. Our study provides insights into the relationship between mRNA and lncRNA networks in the ethylene biosynthetic pathway and anthocyanin accumulation in apple fruit.

PPAR-α Agonist GW7647 Protects Against Oxidative Stress and Iron Deposit via GPx4 in a Transgenic Mouse Model of Alzheimer's Diseases.

Alzheimer's disease (AD) is a neurodegenerative disease caused by lipid peroxidation and iron hemostasis of the brain. PPAR-α is regarded as the most encouraging therapeutic approach of several neurodegenerative and metabolic disorders, due to its potent regulatory effects. In this study, we examined the ameliorative effect and the mechanisms of a PPAR-α agonist, GW7647, on the established AD models using APP/PS1 mice and APPsw/SH-SY5Y cells. Through Aß quantification and behavioral test, we found that GW7647 reduced Aß burden and improved cognitive defect in APP/PS1 mice. Liquid chromatography-mass spectrometry analysis indicated that GW7647 could enter the brain after oral administration. Neuronal cell death and iron deposit were inhibited, accompanied by decreased lipid peroxidation and inflammation. In an in vitro study of APPsw cells, we found that PPAR-α directly bound with GPx4 intron3 to promote GPx4 transcription and reduced the iron transport capability. Our data suggested that activation of PPAR-α by GW7647 improved the disruption of iron homeostasis in the brain of APP/PS1 mice and alleviated neuronal inflammation and lipid peroxidation, which was possibly related to the upregulated transcription of GPx4 mediated by the interaction of GPx4 noncoding region and the PPAR-α.

An adaptive hybrid XdeepFM based deep Interest network model for click-through rate prediction system.

Recent advances in communication enable individuals to use phones and computers to access information on the web. E-commerce has seen rapid development, e.g., Alibaba has nearly 12 hundred million customers in China. Click-Through Rate (CTR) forecasting is a primary task in the e-commerce advertisement system. From the traditional Logistic Regression algorithm to the latest popular deep neural network methods that follow a similar embedding and MLP, several algorithms are used to predict CTR. This research proposes a hybrid model combining the Deep Interest Network (DIN) and eXtreme Deep Factorization Machine (xDeepFM) to perform CTR prediction robustly. The cores of DIN and xDeepFM are attention and feature cross, respectively. DIN follows an adaptive local activation unit that incorporates the attention mechanism to adaptively learn user interest from historical behaviors related to specific advertisements. xDeepFM further includes a critical part, a Compressed Interactions Network (CIN), aiming to generate feature interactions at a vectorwise level implicitly. Furthermore, a CIN, plain DNN, and a linear part are combined into one unified model to form xDeepFM. The proposed end-to-end hybrid model is a parallel ensemble of models via multilayer perceptron. CIN and xDeepFM are trained in parallel, and their output is fed into a multilayer perceptron. We used the e-commerce Alibaba dataset with the focal loss as the loss function for experimental evaluation through online complex example mining (OHEM) in the training process. The experimental result indicates that the proposed hybrid model has better performance than other models.

κ­opioid receptor agonist, U50488H, inhibits pyroptosis through NLRP3 via the Ca2+/CaMKII/CREB signaling pathway and improves synaptic plasticity in APP/PS1 mice.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder with slow onset in most cases. Clinically, dementia associated with AD is characterized by memory disorders, aphasia, executive dysfunction and personality and behavior changes. Currently, treatment strategies attempt to reduce certain symptoms, however there is no cure for AD. The aim of the present study was to identify a novel treatment strategy for AD. Thus, the protective effects of a κ­opioid receptor (KOR) agonist, U50488H on neural damage in AD mice were investigated. The underlying mechanism of the Ca2+/calcium/calmodulin­dependent protein kinase II/cyclic adenosine monophosphate­response element binding protein (Ca2+/CaMKII/CREB) signaling pathway was evaluated. Amyloid precursor protein (APP)/presenilin­1 (PS1) mice were treated subcutaneously with a KOR agonist for 28 days. The learning and memory abilities of the APP/PS1 mice were evaluated using the Morris water maze test. Damage to hippocampal neurons was assessed using hematoxylin and eosin staining. Inflammatory factors and brain injury markers were detected using ELISA. Neurons were examined using immunofluorescence and dendritic spines were observed using Golgi­Cox staining. Western blotting was used to detect NOD­, LRR­ and pyrin domain­containing protein 3, microglial ptosis and the Ca2+/CaMKII/CREB­related protein pathway. The KOR agonist significantly improved the brain injury observed in APP/PS1 mice, inhibited microglia pyroptosis and improved the synaptic plasticity of APP/PS1 mice, which was reversed by a KOR antagonist. Thus, the KOR agonist improved the symptoms of APP/PS1 mice by inhibiting the Ca2+/CaMKII/CREB signaling pathway.

Epitranscriptomic m6A regulation following spinal cord injury.

RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

Selenium and bone health: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Bone health affects the ability of human body to stay active, and its degradation can cause considerable morbidity and mortality. The factors related to bone health play an important role in preventing osteoporosis and its adverse consequences. However, the risk factors for osteoporosis have not been fully elucidated. Deficiency in the trace element selenium may be one of the risk factors for the development of osteoporosis. Previous studies have investigated the effects of selenium on osteoporosis; however, the results are inconclusive. Therefore, the present study aimed to systematically examine the existing literature on the associations between dietary or serum selenium and bone mineral density (BMD), osteoporosis or osteoporotic fractures, and to quantify such associations through meta-analysis. METHODS AND ANALYSIS: PubMed, Embase and Cochrane Library will be searched using a specified search strategy to identify relevant studies up to October 2019. Both interventional and observational studies in humans will be included. The outcomes will include BMD and the prevalence or incidence of osteoporosis and osteoporotic fractures. For dietary or serum selenium and BMD, osteoporosis or osteoporotic fractures pooled analyses, estimates will be expressed as the mean difference, and the pooled OR, relative risk, HR or beta coefficient, and corresponding 95% CIs. Heterogeneity of the studies and publication bias will be investigated accordingly. To assess the quality and the risk of bias of the included studies, the Newcastle-Ottawa Quality Scale or the Cochrane risk of bias assessment tool will be used where appropriate. ETHICS AND DISSEMINATION: Since no private and confidential patient data will be included in the reporting, approval from an ethics committee is not required. The results will be published in a peer-reviewed journal. The study raises no ethical issues. PROSPERO REGISTRATION NUMBER: CRD42019147188.

Astrocytic reprogramming combined with rehabilitation strategy improves recovery from spinal cord injury.

After spinal cord injury (SCI), the irreversible loss of neurons and the dense glial scar are two of the leading causes of axon regeneration failure. The adult mammalian spinal cord lacks the ability to spontaneously produce new neurons, making it a key challenge to provide new neurons for spinal cord regeneration. Additionally, the dual role of the glial scar (both inhibitory and protective) makes it difficult to manipulate it for therapeutic purposes. In this study, using a single transcription factor Sry-related HMG-box 2 (Sox2) delivered by adeno-associated virus (AAV), we reprogrammed some of the astrocytes targeted by the viral vectors in the glial scar into neurons in a severe SCI model. We show that this astrocytic reprogramming alone can propel axon regeneration by not only replenishing the lost neurons, but also moderately reducing the density of the glial scar without interrupting its integrity. Beyond that, astrocytic reprogramming can significantly improve functional recovery when combined with running wheel rehabilitation, which provides use-dependent plasticity. These findings may provide us with a new idea for how to manipulate the glial scar and a promising therapeutic strategy that combines biological intervention with a rehabilitation strategy.