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Objective To study the effect of ghrelin gene knockout on the postsynaptic potential of dopaminergic neurons in the substantia nigra of mice. Methods Substantia nigra tissue was taken from 10-week-old ghrelin-/- male mice (ghrelin-/- group) and their male wild-type (WT) littermates (WT group). RNA-seq technique was used to screen differently expressed genes (DEGs). KEGG pathway enrichment analysis was performed for the neuronal synaptic activity-associated signaling pathways which DEGs might be involved in. Quantitative real-time PCR (RT-qPCR) was used for validation of the identified DEGs, and western blotting was used for protein expression of neuronal synaptic activity-related genes. Results Compared with the WT group, the ghrelin-/- group had significant changes in the expression levels of 23 genes in the synaptic signaling pathway of dopaminergic neurons. Specifically, Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid type subunit 3 (GluA3) and glycogen synthase kinase3-β (GSK-3β) regulated α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor and N-methyl-D-aspartic acid receptor on the postsynaptic membrane of neurons, respectively. GluA3 and GSK-3β genes were significantly downregulated in the substantia nigra tissue of mice in the ghrelin-/- group. RT-qPCR results showed that compared to the WT group, the ghrelin-/- group had significant downregulation of the mRNA expression levels of GluA3 and GSK-3β in the substantia nigra tissue of mice (t =2.408,2.740,P

AbstractBackground To investigate the effectiveness of the intervention with critical value management and push short messaging service (SMS), and to determine improvement in the referral rate of patients with positive hepatitis C antibody (anti-HCV).Methods No intervention was done for patients with positive anti-HCV screening results from 1 January 2015 to 31 October 2021. Patients with positive anti-HCV results at our hospital from 1 November 2021 to 31 July 2022 were informed vide critical value management and push SMS. For inpatients, a competent physician was requested to liaise with the infectious disease physician for consultation, and patients seen in the OPD (outpatient department) were asked to visit the liver disease clinic. The Chi-square correlation test, one-sided two-ratio test and linear regression were used to test the relationship between intervention and referral rate.Results A total of 638,308 cases were tested for anti-hepatitis C virus (HCV) in our hospital and 5983 of them were positive. 51.8% of the referred patients were aged 18–59 years and 10.8% were aged ≥75 years. The result of Chi-square correlation test between intervention and referral was p = .0000, p

BackgroundAssociated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs).ObjectiveAn analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings.MethodsThe FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance.ResultsTwenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation.ConclusionThis investigation delivers an exhaustive and indicative assessment of galsulfase’s safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.

Abstract The relationship between housing prices (HP) and household non-housing consumption (CON) is a key topic worldwide. By developing a panel threshold model and utilizing data from 18 provinces in central and western China from 2005 to 2020, this study investigates the impact of housing prices on household non-housing consumption given housing credit constraints. The results show that (1) housing credit constraints play a single threshold role in the impact of housing prices on household non-housing consumption; (2) the elasticity of housing price fluctuation on household non-housing consumption was negative in the western region during the entire sample period, and the elasticity of housing price fluctuation on household non-housing consumption decreased when housing credit constraints exceeded its threshold value; (3) the effects of housing price fluctuation on household non-housing consumption in the central region changed from negative to positive when housing credit constraints exceeded its threshold value. These outcomes implies that housing credit constraints are not a factor driving a low household non-housing consumption rate in the studied regions. Importantly, our findings suggest that unaffordable housing prices and homeownership linked to better public education resources in combination were a key factor leading to a low non-housing consumption rate in the studied regions. The main contribution of this paper is to supplement the current academic research on low levels of consumption in underdeveloped regions of China and the impact of housing prices on consumption.

Objective To investigate the effect of OTUD3 knockout on the expression of connexin 43 (Cx43) in neural stem cells (NSCs). Methods Brain cortex tissue protein was isolated and extracted from wild-type (WT) and OTUD3-/- embryonic mice on day 14 of gestation, and WT-NSCs and OTUD3-/--NSCs were cultured in vitro and subcultured according to cell status. After subculture to the third generation, an inverted microscope was used to observe the growth state of OTUD3-/--NSCs and WT-NSCs on days 1 and 3. Immunofluorescent staining was used to measure the expression of Ki67, Nestin, and β-tubulin Ⅲ in WT-NSCs and OTUD3-/--NSCs, and Western blotting was used to measure the changes in the expression of OTUD3 and Cx43 in WT-NSCs,OTUD3-/--NSCs, and the cerebral cortex of WT and OTUD3-/- embryonic mice. Results WT-NSCs and OTUD3-/--NSCs cultured and subcultured to the third generation showed a good growth status, and immunofluorescent staining showed positive staining of Ki67, Nestin, and β-tubulin Ⅲ. Compared with WT-NSCs,OTUD3-/--NSCs had significant reductions in the expression levels of OTUD3 and Cx43 (t=16.82,3.21,P

Objective To investigate the differentially expressed genes (DEGs) in the substantia nigra of mice with Parkinson’s disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) based on bioinformatics, as well as their role in the pathological and progression of PD. Methods GEO database was used to obtain the gene expression microarray data in the substantia nigra of mice in the normal group and the PD model group, and the bioinformatics method was used to screen for DEGs in the substantia nigra between the normal group and the PD model. Metascape tool was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis. Quantitative real-time PCR was used to measure the mRNA expression levels of key functional genes regulating neuronal apoptosis and prion transmission. Results There were 174 upregulated DEGs and 173 downregulated DEGs in the substantia nigra of mice with MPTP-induced PD (P0.26). The upregulated genes were significantly enriched in the pathways regulating prion transmission, neuronal development, iron homeostasis, and export across the plasma membrane, while the downregulated genes were significantly enriched in the pathways regulating synaptic vesicle release, transsynaptic complex transmission, neuronal apoptosis, and actin in cytoskeleton. Compared with the normal group, the PD model group had significant reductions in the expressions of Bdnf and Fbxw7 in the substantia nigra of mice (t=2.25,2.39,P0.05). Conclusion There are significant changes in the key functional genes Bdnf and Fbxw7 that regulate neuronal apoptosis in PD model, which lays a foundation for further clarifying their role in the pathological progression of PD.

The goal of the present study is to examine differences in cognitive, psychomotor, and social-emotional development scores between only children and children with siblings aged 6-30 months in rural China using data of 1802 children across 351 villages in 174 townships, disaggregating according to child gender. The results indicate that having a sibling is negatively associated with cognitive, psychomotor, and socioemotional development for girls, but not for boys. Despite this, girls appear to be developmentally advantaged compared to boys, even when they have a sibling. Our results, however, are not conclusive regarding why only-girls are affected while boys are not affected by the existence of siblings. Parenting behaviours (such as playing with children, reading to children, reading to children with books, and singing to children), appear to be unrelated to the developmental differences between only-girls and girls with siblings.

ABSTRACT The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Abstract Objective The purpose of the current study was to evaluate the association between C-reactive protein-to-platelet ratio (CPR), neutrophil-to-lymphocyte*platelet ratio (NLPR) and fibrinogen-to-platelet ratio (FPR) and the prognoses of pyogenic liver abscess (PLA) patients. Methods A cohort of 372 patients with confirmed PLA were enrolled in this retrospective study between 2015 and 2021. Laboratory data were collected on admission within 24 h. The demographic characteristics and clinical features were recorded. Risk factors for outcomes of PLA patients were determined via multivariate logistic regression analyses, and optimal cut-off values were estimated by using the receiver operating characteristic (ROC) curve analysis. Results Out of 372 patients, 57.8% were men, 80 (21.5%) developed sepsis, and 33 (8.9%) developed septic shock. The levels of CPR, NLPR and FPR were significantly increased in the development of sepsis, and prolonged hospital stays in PLA patients. The multivariate logistic regression analysis indicated that the CPR (OR: 2.262, 95% CI: 1.586–3.226, p

ABSTRACT With the globally prevailing carbapenemase-producing (CP) Citrobacter spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was conducted to investigate the prevalence of mcr-9 in Citrobacter species. From October to November 2021, 650 fecal samples and 215 Citrobacter isolates were collected from healthy individuals and infected patients, respectively. Isolates were screened for the presence of the mcr-9 gene by the PCR method. mcr-9-carrying strains were identified by matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. Due to the susceptibility to colistin, Citrobacter spp. isolates were first induced to increase the expression of mcr-9 on China blue agar plates containing colistin and were then subjected to conjugation experiments. Whole-genome sequencing was performed on the Illumina NovaSeq PE150 system. The prevalence of mcr-9 in the Citrobacter genus from healthy guts and infected patients was 0.62% and 1.86%, respectively. In all mcr-9-positive strains, MICs of polymyxin B were observed at ≤2 μg/mL, displaying a nonresistant phenotype. As for conjugation experiments, only one isolate successfully transferred the mcr-9 gene to Escherichia coli C600. Whole-genome sequencing showed that eight mcr-9-positive Citrobacter isolates carried mcr-9 and genes encoding resistance to beta-lactam antibiotics, including blaCMY, blaDHA, blaSHV, blaTEM, and blaCTX-M. We also discovered that mcr-9 could be located on the pKPC-CAV1321 plasmid. Our study investigated the prevalence of mcr-9 in Citrobacter spp. in both healthy individuals and infected patients and described the carriage of mcr-9 on the pKPC-CAV1321 plasmid for the first time. IMPORTANCE The emergence of mcr homologues posed a serious threat to the therapeutic efficiency of polymyxin antibiotics. Citrobacter freundii is generally regarded as an opportunistic pathogen associated with a variety of nosocomial infections. In this study, we investigated the prevalence of mcr-9 in Citrobacter spp. isolates from healthy individuals and infected patients and highlighted the importance of the rational use of antibiotics. In addition, this epidemiological investigation is the first to describe the carriage of mcr-9 on plasmid pKPC-CAV1321 and confirms the horizontal transfer of this plasmid. Our research may shed new light on further studies of mcr-9 dissemination in humans.

ObjectiveMetagenomic next-generation sequencing (mNGS) technology has the potential to detect a wide range of pathogenic microorganisms. However, reports on the diagnostic value and clinical significance of different platforms of mNGS for patients with lower respiratory tract infections (LRTIs) remain scarce.MethodsA total of 306 patients with suspected LRTIs were enrolled from January 2019 to December 2021. The diagnostic performance of conventional methods and mNGS on bronchoalveolar lavage fluid (BALF) were compared. BALF mNGS was performed using a commercial and an in-house laboratory. The diagnostic value and the clinical implications of mNGS for LRTIs were analyzed for the different platforms.ResultsThe positive rate of mNGS in the in-house group was higher than that in the commercial group (85.26% vs. 70.67%, p < 0.001). mNGS significantly increased the pathogen detection rate compared with conventional methods [from 70.67% vs. 22.67% (p < 0.001) to 85.26% vs. 30.77% (p < 0.001)]. The pathogens detected using mNGS included bacteria, fungi, viruses, and atypical pathogens. The in-house platform performed well on a wider spectrum of microbial distribution. Furthermore, it showed an advantage in detecting mixed pathogens in immunocompromised patients. Among the mNGS positive cases, 34 (32.0%) cases had their antibiotics adjusted in the commercial group, while 51 (38.3%) cases had a change of treatment in the in-house group. Moreover, the turnaround time of mNGS and the time from mNGS to discharge in the in-house group were significantly shorter than those in the commercial group.ConclusionIn-house mNGS had a higher detection rate and can show a wider spectrum of pathogens, with potential benefits for the clinic by shortening the turnaround time and hospitalization, and it may be more suitable for clinical microbiology laboratories.

Abstract With an increasing aging society, China is the world’s fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.

Abstract Background Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. Methods This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. Results A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p

BackgroundLoss of masticatory function consequent to tooth loss has been associated with changes in food choices and insufficient nutritional intake. To date, interventions based on dental prostheses alone did not significantly improve nutrient intake. Pilot studies have shown positive impacts of interventions combining implant-supported fixed dental prosthesis with brief dietary advice. The relative contribution and the potential synergy of the components of such interventions need to be determined as it has major public health implications for the community-dwelling aging population that continues to disproportionately suffer from tooth loss and its consequences.ObjectiveTo assess the effect of rehabilitation of masticatory function with fixed implant supported dentures and nutrition education in older subjects with terminal dentition (stage IV periodontitis) or full edentulism.MethodsA 2 × 2 factorial randomized controlled trial with 16-month follow-up of eligible adults (≥60 years) with loss of masticatory function consequent to full arch edentulism or terminal dentition (n = 120) will be conducted to test whether the rehabilitation of masticatory function with fixed implant supported dentures, nutrition education and/or their combination improves intake of fresh fruits and vegetables for aging subjects. The study has been designed to detect changes in fresh fruits and fresh vegetables intake at 4 months using the 24-h dietary recall method. Changes in protein as percentage of total energy, nutritional biomarkers, plasma metabolomics, oral and gut microbiome, quality of life and masticatory function will also be assessed.DiscussionWe hypothesize that receiving rehabilitation of masticatory function with fixed implant dentures together with nutrition education is the most effective intervention for improving nutrient intake in aging community-dwelling subjects with extensive tooth loss. The results of this study will assist in designing better treatment regimens, guide medical care for individual subjects, and inform public health and policy.Clinical Trials RegistrationNCT05334407.

Abstract Objectives This study aims to evaluate the ability of tantalum-coated titanium to improve human gingival fibroblasts’ adhesion, viability, proliferation, migration performance, and the potential molecular mechanisms. Materials and methods Titanium plates were divided into two groups: (1) no coating (Ti, control), (2) Tantalum-coated titanium (Ta-coated Ti). All samples were characterized by scanning electronic microscopy, surface roughness, and hydrophilicity. Fibroblasts’ performance were analyzed by attached cell number at 1 h, 4 h, and 24 h, morphology at 1 h and 4 h, viability at 1 day, 3 days, 5 days, and 7 days, recovery after wounding at 6 h, 12 h, and 24 h. RT-PCR, western blot were applied to detect attachment-related genes’ expression and protein synthesis at 4 h and 24 h. Student’s t test was used for statistical analysis. Results Tantalum-coated titanium demonstrates a layer of homogeneously distributed nano-grains with mean diameter of 25.98 (± 14.75) nm. It was found that after tantalum deposition, human gingival fibroblasts (HGFs) adhesion, viability, proliferation, and migration were promoted in comparison to the control group. An upregulated level of Integrin β1 and FAK signaling was also detected, which might be the underlying mechanism. Conclusion In the present study, adhesion, viability, proliferation, migration of human gingival fibroblasts are promoted on tantalum-coated titanium, upregulated integrin β1 and FAK might contribute to its superior performance, indicating tantalum coating can be applied in transmucosal part of dental implant. Clinical significance Tantalum deposition on titanium surfaces can promote human gingival fibroblast adhesion, accordingly forming a well-organized soft tissue sealing and may contribute to a successful osseointegration.