Search

Objectives: Comorbidities, as components of these heterogeneous features, often coexist with knee osteoarthritis, and are particularly prevalent in end-stage knee osteoarthritis. Here, we attempted to identify the different clinical phenotypes of comorbidities in patients with end-stage knee osteoarthritis by cluster analysis. Methods: A total of 421 inpatients diagnosed with end-stage knee osteoarthritis who underwent inpatient surgery were included in this cross-sectional study. 23 demographic, comorbidity, inflammatory immune and evaluation scale variables were collected. Systematic clustering after factor analysis and separate two-step cluster analysis were performed for individual comorbidity variables and all variables, respectively, to objectively identify the different clinical phenotypes of the study patients. Results: Four clusters were finally identified. Cluster 1 had the largest proportion of obese patients (93.8%) and hypertension was common (71.2%). Almost all patients in cluster 2 were depressed (95.8%) and anxiety disorders (94.7%). Cluster 3 combined patients with isolated end-stage knee osteoarthritis and a few comorbidities. Cluster 4 had the highest proportion of patients with rheumatoid arthritis (58.8%). Conclusions: Patients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: "isolated end-stage knee osteoarthritis"; "obesity + hypertension"; "depression + anxiety"; and "rheumatoid arthritis", which may help guide individualized patient care and treatment strategies. [ABSTRACT FROM AUTHOR]

Background: To compare the clinical and radiological outcomes of monoplanar screws (MSs) versus hybrid fixed axial and polyaxial screws (HSs) in percutaneous short-segment intermediate screw fixation (PSISF) for traumatic thoracolumbar burst fractures (TTBFs) in patients without neurologic impairment. Methods: A consecutive series of 100 patients with single-segment TTBFs and no neurologic impairment who underwent PSISF with 6 monoplanar screws (MS group) or correct were retrospectively enrolled. The demographic data, radiologic evaluation indicators, perioperative indicators and clinical assessment indicators were analysed between the MS group and HS group. Results: The demographic data and perioperative indicators were not significantly different in the two groups (P > 0.05). The postoperative anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were significantly improved in both groups (*P < 0.05). The MS group obtained better correction than the HS group in terms of improvement in the AVHR, KCA and VWA after surgery (*P < 0.05). At the last follow-up, the MS group had less correction loss of AVHR, KCA and VWA (*P < 0.05). The MS group presented greater improvement in the SCER at the last follow-up (*P < 0.05). The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) score of all patients were significantly better postoperatively than those preoperatively (*P < 0.05), and the scores collected at each follow-up visit did not differ significantly between the two groups (P > 0.05). In the MS group, no internal fixation failure was observed during the follow-up period, but, in the HS group, two cases of internal fixation failure were observed at the last follow-up (one case of rod loosening and one case of screw breakage). Conclusions: Both MSs and HSs fixation are effective treatments for TTBFs and have comparable clinical outcomes. In contrast, MSs fixation can improve the correction effect, better improve the SCER, and further reduce correction loss as well as reduce the incidence of instrumentation failure. Therefore, MSs fixation might be a better option for treating TTBFs in patients without neurological deficits. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is chronic arthritis characterized by articular cartilage degradation. However, a comprehensive regulatory network for OA-related microRNAs and DNA methylation modifications has yet to be established. Thus, we aimed to identify epigenetic changes in microRNAs and DNA methylation and establish the regulatory network between miRNAs and DNA methylation. The mRNA, miRNA, and DNA methylation expression profiles of healthy or osteoarthritis articular cartilage samples were downloaded from Gene Expression Omnibus (GEO) database, including GSE169077, GSE175961, and GSE162484. The differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs), and differentially methylated genes (DMGs) were analyzed by the online tool GEO2R. DAVID and STRING databases were applied for functional enrichment analysis and protein-protein interaction (PPI) network. Potential therapeutic compounds for the treatment of OA were identified by Connectivity map (CMap) analysis. A total of 1424 up-regulated DEGs, 1558 down-regulated DEGs, 5 DEMs with high expression, 6 DEMs with low expression, 1436 hypermethylated genes, and 455 hypomethylated genes were selected. A total of 136 up-regulated and 65 downregulated genes were identified by overlapping DEGs and DEMs predicted target genes which were enriched in apoptosis and circadian rhythm. A total of 39 hypomethylated and 117 hypermethylated genes were obtained by overlapping DEGs and DMGs, which were associated with ECM receptor interactions and cellular metabolic processes, cell connectivity, and transcription. Moreover, The PPI network showed COL5A1, COL6A1, LAMA4, T3GAL6A, and TP53 were the most connective proteins. After overlapping of DEGs, DMGs and DEMs predicted targeted genes, 4 up-regulated genes and 11 down-regulated genes were enriched in the Axon guidance pathway. The top ten genes ranked by PPI network connectivity degree in the up-regulated and downregulated overlapping genes of DEGs and DMGs were further analyzed by the CMap database, and nine chemicals were predicted as potential drugs for the treatment of OA. In conclusion, TP53, COL5A1, COL6A1, LAMA4, and ST3GAL6 may play important roles in OA genesis and development. [ABSTRACT FROM AUTHOR]

Objectives: The study was to explore the influence of microRNA (miR)-345-3p on proinflammatory cytokines in patients with rheumatoid arthritis (RA). Methods: A total of 32 RA patients and 32 healthy patients were enrolled. Proinflammatory factors in patients' serum were detected by ELISA, and miR-345-3p was detected by RT-qPCR. The correlation between miR-345-3p expression and proinflammatory factors in RA patients was analyzed. The diagnostic value of miR-345-3p and proinflammatory factors in RA patients was analyzed by receiver operating curve diagnosis. The predictive value of miR-345-3p levels and proinflammatory factors in RA patients was analyzed by multivariate Cox regression. HFLS-RA and HFLS cells were cultured, in which miR-345-3p and proinflammatory cytokines were detected by RT-qPCR. Cell proliferation and apoptosis were determined by CCK-8 and flow cytometry, respectively. Results: MiR-345-3p was lowly expressed in the serum of RA patients. MiR-345-3p and proinflammatory factors were of diagnostic and predictive values in RA. Elevated miR-345-3p restrained the production of proinflammatory factors of HFLS-RA cells, improved cell proliferation, and reduced apoptosis. Conclusion: MiR-345-3p is a potential biomarker and ameliorates RA by reducing the release of proinflammatory cytokines. Highlights: miR-345-3p was reduced in the serum of RA patients; Serum miR-345-3p in RA patients was negatively correlated with proinflammatory factors; MiR-345-3p and proinflammatory factors were of diagnostic value in RA; Elevated miR-345-3p suppressed the release of proinflammatory cytokines in HFLS-RA cells; MiR-345-3p ameliorated RA. [ABSTRACT FROM AUTHOR]

Background: Microwave ablation (MWA) via ultrasound guidance is an important tool in the treatment of liver metastases. The most common postoperative complications are abdominal hemorrhage and bile leakage, whereas thrombosis in the suprahepatic inferior vena cava (IVC) is very rare, and clinical management is very difficult when the head end of the thrombus reaches the right atrium. Case presentation: This is a case report of a 52-year-old man with hepatic metastasis 21 months after radical resection of rectal cancer. After chemotherapy combined with targeted therapy, metastasis in segment IV (S4) of the liver was treated with microwave ablation. Two months after treatment, the hepatic metastasis in S4 showed a microwave ablation zone on MRI.Enhanced MRI showed venous thrombosis located in the left hepatic vein and IVC, and the head of the thrombus reached the right atrium. After two weeks of anticoagulation and thrombolytic treatment, the follow-up MRI showed that the venous thrombus had nearly disappeared. Conclusion: When liver metastases are close to the hepatic vein, clinicians should pay attention to the occurrence of hepatic vein and IVC thrombosis following MWA; through early diagnosis and anticoagulation, pulmonary thromboembolism (PTE) can be minimized. [ABSTRACT FROM AUTHOR]

Background: The bidirectional causal association between daytime napping frequency and schizophrenia is unclear. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted with summary statistics of top genetic variants associated with daytime napping frequency and schizophrenia from genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) data of daytime napping frequency GWAS came from the UK Biobank (n = 452,633) and 23andMe study cohort (n = 541,333), while the schizophrenia GWAS came from the Psychiatric Genomics Consortium (PGC, 36,989 cases and 113,075 controls). The inverse variance weighted (IVW) analysis was the primary method, with the weighted median, MR-Robust Adjusted Profile Score (RAPS), Radial MR and MR-Pleiotropy Residual Sum Outlier (PRESSO) as sensitivity analysis. Results: The MR analysis showed a bidirectional causal relationship between more frequent daytime napping and the occurrence of schizophrenia, with the odds ratio (OR) for one-unit increase in napping category (never, sometimes, usually) on schizophrenia was 3.38 (95% confidence interval [CI]: 2.02–5.65, P = 3.58 × 10–6), and the beta for the occurrence of schizophrenia on daytime napping frequency was 0.0112 (95%CI: 0.0060–0.0163, P = 2.04 × 10–5). The sensitivity analysis obtained the same conclusions. Conclusion: Our findings support the bidirectional causal association between more daytime napping frequency and schizophrenia, implying that daytime napping frequency is a potential intervention for the progression and treatment of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved. Methods: In the all trans retinal (atRAL)-induced oxidative stress model, we used the vector of lentivirus to knockdown the expression of SHP-1 in ARPE-19 cells. CCK-8 assay, Annexin V/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis. Results: We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes. Conclusions: These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal diseases including AMD. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved. Methods: In the all trans retinal (atRAL)-induced oxidative stress model, we used the vector of lentivirus to knockdown the expression of SHP-1 in ARPE-19 cells. CCK-8 assay, Annexin V/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis. Results: We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes. Conclusions: These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal diseases including AMD. [ABSTRACT FROM AUTHOR]

Background: The study of symbiotic nitrogen fixation between (SNF) legumes and rhizobia has always been a hot frontier in scientific research. Nanotechnology provides a new strategy for biological nitrogen fixation research. However, how to construct abiotic nano-structure-biological system, using the special properties of nanomaterials, to realize the self-enhancement of biological nitrogen fixation capacity is important. Results: In order to construct a more efficient SNF system, in this study, we applied manganese ferrite nanoparticles (MF-NPs) with sustainable diatomic catalysis to produce reactive oxygen species (ROS), thus regulating the nodulation pathway and increasing the number of nodules in soybean (Glycine max), eventually enhancing symbiotic nitrogen fixation. Symbiosis cultivation of MF-NPs and soybean plants resulted in 50.85% and 61.4% increase in nodule weight and number, respectively, thus inducing a 151.36% nitrogen fixation efficiency increase, finally leading to a 25.70% biomass accumulation increase despite no substantial effect on the nitrogenase activity per unit. Transcriptome sequencing analysis showed that of 36 differentially expressed genes (DEGs), 31 DEGs related to soybean nodulation were upregulated in late rhizobium inoculation stage (12 d), indicating that the increase of nodules was derived from nodule-related genes (Nod-R) continuous inductions by MF-NPs. Conclusions: Our results indicated that the nodule number could be effectively increased by extending the nodulation period without threatening the vegetative growth of plants or triggering the autoregulation of nodulation (AON) pathway. This study provides an effective strategy for induction of super-conventional nodulation. [ABSTRACT FROM AUTHOR]

Background: Although the high offset Tri-Lock bone preservation stem (BPS) was used widely, few studies explored the clinical and radiological results. The purpose of this study was to determine the clinical and radiological results of high offset Tri-Lock BPS in unilateral primary total hip arthroplasty (THA) at a minimum follow-up of 3 years. Methods: 55 patients who underwent cementless THA with high offset Tri-lock BPS from 2017 to 2018 were followed for a minimum follow-up of 3 years. Patients were assessed clinically for complications, Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Oxford Hip Score (OHS). Femoral offset (FO), acetabular offset (AO), hip offset (HO), HO difference, and leg length discrepancy (LLD) were measured on the anteroposterior (AP) pelvic radiograph. Standard pelvic AP and lateral radiographs were used to evaluate for evidence of bone ingrowth, stem subsidence, stem alignment, radiolucent line around the stem, osteolysis, loosening, ectopic ossification, and femoral stress shielding. Results: No patients reported complications during hospitalization nor the follow-up period. At a mean follow-up of 42.5 months, the mean HHS, WOMAC, and OHS scores showed a significant improvement from preoperative to the latest follow-up. No patients reported thigh pain. No revision nor sign of radiographic loosening had been detected. The high offset Tri-Lock BPS significantly improved the FO and HO postoperatively. HO difference and LLD were balanced postoperatively. No sign of stem subsidence, radiolucent line, osteolysis, loosening, ectopic ossification, nor severe stress shielding (more than grade 3–4) were observed at the latest follow-up. Conclusion: The high offset Tri-Lock BPS demonstrated excellent clinical and radiographic outcomes at a minimum follow-up of 3 years. HO difference and LLD between legs decreased significantly and achieved balance postoperatively. Long-term follow-up is required for a definitive conclusion. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the main causes of death worldwide. Combination drug therapy has been a mainstay of cancer treatment for decades and has been shown to reduce host toxicity and prevent the development of acquired drug resistance. However, the immense number of possible drug combinations and large synergistic space makes it infeasible to screen all effective drug pairs experimentally. Therefore, it is crucial to develop computational approaches to predict drug synergy and guide experimental design for the discovery of rational combinations for therapy. Results: We present a new deep learning approach to predict synergistic drug combinations by integrating gene expression profiles from cell lines and chemical structure data. Specifically, we use principal component analysis (PCA) to reduce the dimensionality of the chemical descriptor data and gene expression data. We then propagate the low-dimensional data through a neural network to predict drug synergy values. We apply our method to O'Neil's high-throughput drug combination screening data as well as a dataset from the AstraZeneca-Sanger Drug Combination Prediction DREAM Challenge. We compare the neural network approach with and without dimension reduction. Additionally, we demonstrate the effectiveness of our deep learning approach and compare its performance with three state-of-the-art machine learning methods: Random Forests, XGBoost, and elastic net, with and without PCA-based dimensionality reduction. Conclusions: Our developed approach outperforms other machine learning methods, and the use of dimension reduction dramatically decreases the computation time without sacrificing accuracy. [ABSTRACT FROM AUTHOR]

Background: Ultrasonography for neuraxial anesthesia is increasingly being used to identify spinal structures and the identification of correct point of needle insertion to improve procedural success, in particular in obesity. We developed an ultrasound-guided automated spinal landmark identification program to assist anesthetists on spinal needle insertion point with a graphical user interface for spinal anesthesia. Methods: Forty-eight obese patients requiring spinal anesthesia for Cesarean section were recruited in this prospective cohort study. We utilized a developed machine learning algorithm to determine the needle insertion point using automated spinal landmark ultrasound imaging of the lumbar spine identifying the L3/4 interspinous space (longitudinal view) and the posterior complex of dura mater (transverse view). The demographic and clinical characteristics were also recorded. Results: The first attempt success rate for spinal anesthesia was 79.1% (38/48) (95%CI 65.0 - 89.5%), followed by successful second attempt of 12.5% (6/48), third attempt of 4.2% (2/48) and 4th attempt (4.2% or 2/48). The scanning duration of L3/4 interspinous space and the posterior complex were 21.0 [IQR: 17.0, 32.0] secs and 11.0 [IQR: 5.0, 22.0] secs respectively. There is good correlation between the program recorded depth of the skin to posterior complex and clinician measured depth (r = 0.915). Conclusions: The automated spinal landmark identification program is able to provide assistance to needle insertion point identification in obese patients. There is good correlation between program recorded and clinician measured depth of the skin to posterior complex of dura mater. Future research may involve imaging algorithm improvement to assist with needle insertion guidance during neuraxial anesthesia. Trial registration: This study was registered on clinicaltrials.gov registry (NCT03687411) on 22 Aug 2018. [ABSTRACT FROM AUTHOR]

Background: To analyze the clinical effect of two different ways of minimally invasive transthoracic closure in children with ventricular septal defect (VSD).Methods: From January 2015 to July 2019, 294 children with VSD were enrolled in the Fujian Medical University Union Hospital. Patients were divided into two groups - those who underwent VSD closure through the left sternal fourth intercostal incision (group A: n = 95) and the lower sternal incision (group B: n = 129).Results: The operation time, bleeding volume, postoperative mechanical ventilation time, postoperative intensive care unit (ICU) monitoring time, postoperative hospitalization time and complication rate in group A were significantly lower than those in group B (P < 0.05). There was no significant difference between the two groups in the operation success rate, mechanical ventilation time and total hospitalization cost (P > 0.05).Conclusion: The transthoracic closure of ventricular septal defect through the left sternal fourth intercostal incision is feasible, safe, cosmetic, and worth popularizing. [ABSTRACT FROM AUTHOR]

Background: Exosomes play important roles in angiogenesis, drug resistance, and metastasis of colorectal cancer (CRC), but the underlying mechanism has seldom been reported. Herein, our study aimed to reveal an exosomal miRNA-mRNA network involved in CRC by performing bioinformatical analysis. Methods: The mRNA and miRNA data of colon adenocarcinoma and rectal adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) database, and exosomal miRNAs data were downloaded from the GEO dataset GSE39833. The differential expression analysis was performed using "limma" and "edgeR". Target mRNAs of miRNAs were predicted using FunRich 3.1.3, miRNAtap and multiMiR. The candidate mRNAs and exosomal miRNAs were obtained by intersecting two groups of differentially expressed miRNAs and intersection of the differential expressed mRNAs and the target mRNAs, respectively. Key mRNAs and exosomal miRNAs were identified by the least absolute shrinkage and selection operator regression analysis, and used to construct the exosomal miRNA-mRNA network. The network verified was by receiver operating characteristic curve, GEPIA and LinkedOmics. Functional enrichment analysis was also performed for studied miRNAs and mRNAs. Results: A total of 6568 differentially expressed mRNAs and 531 differentially expressed miRNAs from TCGA data, and 166 differentially expressed exosomal miRNAs in GSE39833 dataset were identified. Next, 16 key mRNAs and five key exosomal miRNAs were identified from the 5284 candidate mRNAs and 61 candidate exosomal miRNAs, respectively. The exosomal miRNA-mRNA network with high connectivity contained 13 hub mRNAs (CBFB, CDH3, ETV4, FOXQ1, FUT1, GCNT2, GRIN2D, KIAA1549, KRT80, LZTS1, SLC39A10, SPTBN2, and ZSWIM4) and five hub exosomal miRNAs (hsa-miR-126, hsa-miR-139, hsa-miR-141, hsa-miR-29c, and hsa-miR-423). The functional annotation revealed that these hub mRNAs were mainly involved in the regulation of B cell receptor signaling pathway and glycosphingolipid biosynthesis related pathways. All hub mRNAs and hub exosomal miRNAs exhibited high diagnosis value for CRC. Furthermore, the association of the hub mRNAs with overall survival, stages, and MSI phenotype of CRC revealed their important roles in CRC progression. Conclusion: This study constructed an exosomal miRNA-mRNA network which may play crucial roles in the carcinogenesis and progression of CRC, thus providing potential diagnostic biomarkers and therapeutic targets for CRC. [ABSTRACT FROM AUTHOR]

Background: Delirium was characterized with a series of symptoms of a sudden onset of disturbances in attention, a loss in memory loss and defects in other cognitive abilities that were also appeared in the syndrome of anxiety. Even though there are overlapped clinical symptoms existed in anxiety and delirium, the relationship between anxiety and delirium was still unclear. The propose of this study was to investigated the effect of preoperative anxiety on postoperative delirium. Methods: Three hundred and seventy-two adults undergoing total hip arthroplasty were enrolled from October 2019 to May 2020 in the study. The preoperative anxiety was measured with the Hospital Anxiety and Depression Scale-Anxiety (HADS-A). The participants were allocated into anxiety group (HADS-A≧7) and non-anxiety group (HADS-A < 7). The primary outcome was the incidence of the postoperative delirium assessed with the Confusion Assessment Method (CAM). The secondary outcomes were the duration and the severity of delirium evaluated with the Memorial Delirium assessment Scale (MDAS). The risks of delirium were also evaluated with logistic regression analysis. Results: There were 325 patients enrolled in the end, 95 of whom met the criteria for anxiety. The incidence of delirium was 17.8% in all participants. The patients with anxiety had a higher incidence of delirium than the non-anxiety patients (25.3% vs. 14.8%, odds ratio (OR) = 0.51, 95% confidence interval (CI) = 0.92–0.29, p = 0.025). However, no significant differences were found in the duration and the severity of the delirium between the above two groups. The age, alcohol abuse, history of stroke, scores of the HADS-A, and education level were considered to be predictors of delirium. Conclusions: The preoperative anxiety predicted the incidence of the postoperative delirium in total hip arthroplasty patients. The related intervention may be a good point for delirium prophylaxis. Trial registration: It was registered at Chinese Clinical Trial Registry (www.chictr.org.cn) with the name of "the effect of preoperative anxiety on the postoperative cognitive function" (ChiCTR1900026054) at September 19, 2019. [ABSTRACT FROM AUTHOR]

Background: Dissolved oxygen (DO) in the water is a vital abiotic factor in aquatic animal farming. A hypoxic environment affects the growth, metabolism, and immune system of fish. Glycolipid metabolism is a vital energy pathway under acute hypoxic stress, and it plays a significant role in the adaptation of fish to stressful environments. In this study, we used multi-omics integrative analyses to explore the mechanisms of hypoxia adaptation in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus). Results: The 96 h median lethal hypoxia (96 h-LH50) for GIFT was determined by linear interpolation. We established control (DO: 5.00 mg/L) groups (CG) and hypoxic stress (96 h-LH50: 0.55 mg/L) groups (HG) and extracted liver tissues for high-throughput transcriptome and metabolome sequencing. A total of 581 differentially expressed (DE) genes and 93 DE metabolites were detected between the CG and the HG. Combined analyses of the transcriptome and metabolome revealed that glycolysis/gluconeogenesis and the insulin signaling pathway were down-regulated, the pentose phosphate pathway was activated, and the biosynthesis of unsaturated fatty acids and fatty acid metabolism were up-regulated in GIFT under hypoxia stress. Conclusions: The results show that lipid metabolism became the primary pathway in GIFT under acute hypoxia stress. Our findings reveal the changes in metabolites and gene expression that occur under hypoxia stress, and shed light on the regulatory pathways that function under such conditions. Ultimately, this information will be useful to devise strategies to decrease the damage caused by hypoxia stress in farmed fish. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) cultivation with biomaterials was proposed to facilitate stem cell epithelial differentiation for wound healing. However, whether human adipose-derived stem cells (hASCs) on collagen sponge scaffold (CSS) better differentiate to keratinocytes remains unclear. Methods: 3D cultivation with CSS on hASC epidermal differentiation co-cultured with HaCaT cells at air-liquid interface (ALI) was compared with two-dimensional (2D) form and cultivation without "co-culture" or "ALI." Cellular morphology, cell adhesion, and growth condition were evaluated, followed by the protein and gene expression of keratin 14 (K14, keratinocyte specific marker). Results: Typical cobblestone morphology of keratinocytes was remarkably observed in co-cultured hASCs at ALI, but those seeded on the CSS exhibited more keratinocyte-like cells under an invert microscope and scanning electron microscope. Desired cell adhesion and proliferation were confirmed in 3D differentiation groups by rhodamine-labeled phalloidin staining, consistent with H&E staining. Compared with those cultured in 2D culture system or without "ALI," immunofluorescence staining and gene expression analysis revealed hASCs co-cultured over CSS expressed K14 at higher levels at day 15. Conclusions: CSS is positive to promote epithelial differentiation of hASCs, which will foster a deeper understanding of artificial dermis in skin wound healing and regeneration. [ABSTRACT FROM AUTHOR]

Background: Osteotomies in the cervical spine are technically challenging. The purpose of this study was to evaluate the feasibility of the modified pedicle subtraction osteotomy (PSO) technique at C7 to be used for the treatment of cervicothoracic kyphosis secondary to ankylosing spondylitis.Methods: A total of 120 cervical spine computed tomography (CT) scans (of 82 male and 38 female patients) were evaluated. The scans were taken parallel to the middle sagittal plane and the sagittal plane intersecting the pedicles. Simulated osteotomy was performed by setting the apex of the wedge osteotomy at different points, and morphologic measurements were obtained. Seven patients with cervicothoracic kyphosis who underwent a modified PSO at C7 between May 2009 and June 2015 were retrospectively evaluated. The mean follow up was 32.9 months (range 21-54 months). Preoperative and postoperative chin-brow vertical angle (CBVA), sagittal vertical axis (SVA) and sagittal Cobb angle of the cervical region were reviewed. The outcomes were analyzed through various measures, which included the 36-Item Short Form Health Survey (SF-36) and a visual analog scale for neck pain.Results: In this morphometric study, a modified PSO was performed on 87 patients (59 male and 28 female) with a reasonable ratio of 72.5%. In the case series, radiographic parameters and health-related quality-of-life measures were found to show significant postoperative improvement in all patients. No major complications occurred, and no implant failures were noted until the latest follow up.Conclusions: The modified PSO is a safe and valid alternative to the classic PSO, allowing for excellent correction of cervical kyphosis and improvement in health-related quality-of-life measures. [ABSTRACT FROM AUTHOR]

Background: In recent years, mitochondrial dysfunction has been extensively studied and published, but research on the effects of mitochondrial dysfunction on bone metabolism and related diseases is only just beginning. Furthermore, no studies have been carried out to systematically illustrate this area from a scientometric point of view. The goal of this research is to review existing knowledge and identify new trends and possible hotspots in this area.Methods: All publications related to the relationship between mitochondrial dysfunction and bone metabolism and related diseases from 2003 to 2022 were searched at the Web of Science Core Collection (WoSCC) on May 7, 2022. Four different analytical tools: VOSviewer 1.6.18, CiteSpace V 6.1, HistorCite (12.03.07), and Excel 2021 were used for the scientometric research.Results: The final analysis included 555 valid records in total. Journal of Biological Chemistry (Co-citations = 916) is the most famous journal in this field. China (Percentage = 37%), the United States (Percentage = 24%), and Korea (Percentage = 12%) are the most productive countries. Blanco FJ and Choi EM are the main researchers with significant academic influence. Current research hotspots are basic research on mitochondrial dysfunction and the prevention or treatment of bone metabolism-related diseases.Conclusion: The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. Several prominent researchers have published extensive literature and are widely cited. Future research in this area will focus on oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases. [ABSTRACT FROM AUTHOR]

Data are presented as the mean ± SD (n = 3, each group). b The expression of TDGF-1 in human astrocytes (HA) and glioblastoma cell lines (U87 and U251). c The expression of TDGF-1 in glioblastoma cell lines (U87 and U251) and glioblastoma stem cells (GSC-U87, GSC-U251). d CCK-8 assay was used to measure the effect of TDGF-1 on the proliferation of GSC-U87 and GSC-U251 cells. e The apoptotic percentages of GSC-U87 and GSC-U251 were detected after TDGF-1 over-expression or knockdown. f Transwell assays were used to measure the effect of TDGF-1 on cell migration and invasion of GSC-U87 and GSC-U251 cells. TDGF-1(-)NC. h Weatern blot assay were used to detect the TDGF-1 expression regulated by miR-194-5p and SOX3. [Extracted from the article]

Background: Nerve guide conduits are a promising strategy for reconstructing peripheral nerve defects. Improving the survival rate of seed cells in nerve conduits is still a challenge and microcarriers are an excellent three-dimensional (3D) culture scaffold. Here, we investigate the effect of the 3D culture of microcarriers on the biological characteristics of adipose mesenchymal stem cells (ADSCs) and to evaluate the efficacy of chitosan nerve conduits filled with microcarriers loaded with ADSCs in repairing nerve defects. Methods: In vitro, we prepared porous chitosan microspheres by a modified emulsion cross-linking method for loading ADSCs and evaluated the growth status and function of ADSCs. In vivo, ADSCs-loaded microcarriers were injected into chitosan nerve conduits to repair a 12 mm sciatic nerve defect in rats. Results: Compared to the conventional two-dimensional (2D) culture, the prepared microcarriers were more conducive to the proliferation, migration, and secretion of trophic factors of ADSCs. In addition, gait analysis, neuro-electrophysiology, and histological evaluation of nerves and muscles showed that the ADSC microcarrier-loaded nerve conduits were more effective in improving nerve regeneration. Conclusions: The ADSCs-loaded chitosan porous microcarrier prepared in this study has a high cell engraftment rate and good potential for peripheral nerve repair. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients' clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. Methods: In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. Results: A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. Conclusion: The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL. [ABSTRACT FROM AUTHOR]

Background: Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators. Methods: A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators. Results: Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1β) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks. Conclusion: Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators. [ABSTRACT FROM AUTHOR]

Background: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. Methods: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. Results: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (β = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (β = 0.033, 95% CI: 0.003, 0.062), heel-BMD (β = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (β = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (β ranged from − 0.012 to 0.075). Conclusions: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes. [ABSTRACT FROM AUTHOR]

Background: [18 F]-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has the ability to detect local and/or regional recurrence as well as distant metastasis. We aimed to evaluate the prognosis value of PET/CT in locoregional recurrent nasopharyngeal (lrNPC). Methods: A total of 451 eligible patients diagnosed with recurrent I-IVA (rI-IVA) NPC between April 2009 and December 2015 were retrospectively included in this study. The differences in overall survival (OS) of lrNPC patients with and without PET/CT were compared in the I-II, III-IVA, r0-II, and rIII-IVA cohorts, which were grouped by initial staging and recurrent staging (according to MRI). Results: In the III-IVA and rIII-IVA NPC patients, with PET/CT exhibited significantly higher OS rates in the univariate analysis (P = 0.045; P = 0.009; respectively). Multivariate analysis revealed that with PET/CT was an independent predictor of OS in the rIII-IVA cohort (hazard ratio [HR] = 0.476; 95% confidence interval [CI]: 0.267 to 0.847; P = 0.012). In the rIII-IVA NPC, patients receiving PET/CT sacns before salvage surgery had a better prognosis compared with MRI alone (P = 0.036). The recurrent stage (based on PET/CT) was an independent predictor of OS. (r0-II versus [vs]. rIII-IVA; HR = 0.376; 95% CI: 0.150 to 0.938; P = 0.036). Conclusion: The present study showed that with PET/CT could improve overall survival for rIII-IVA NPC patients. PET/CT appears to be an effective method for assessing rTNM staging. [ABSTRACT FROM AUTHOR]

Background: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. Methods: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3–12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. Results: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42–6.02), for FS alone 3.06 (95%CI 1.48–6.31), and for comorbid BA and FS 21.18 (95%CI 9.10–49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). Limitations: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. Conclusion: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor. [ABSTRACT FROM AUTHOR]

Introduction: Few studies focused on the Pre-Exposure Prophylaxis (PrEP) -related aspects, and the applicability of prior evidence to young men who have sex with men (YMSM) students was unknown. This study aimed to assess the awareness, willingness, uptake, and adherence (AWUA) to PrEP among YMSM students in China and to explore the associated factors with these stages. Methods: A cross-sectional survey with a sizable sample of 1151 was conducted among YMSM students aged 16 and above, who self-identified as men who have sex with men(MSM) and resided in mainland China between October 20 and December 20, 2021. The chi-square test and Fisher's exact test were used for univariate analysis, followed by multivariable logistic regression analysis of influencing factors at all levels. Results: According to the cascade analysis approach, 88.71% of the participants were aware of PrEP, among which 66.7% expressed willingness to use it. Among those who were willing to use PrEP, only 13.80% took it, and of those who took it, 44.68% adhered to it. The students taking PrEP were those with higher education (OR = 4.239, 95% CI: 1.334–13.467), residence in pilot cities (OR = 2.791, 95% CI: 1.498–5.198), residence in high-risk areas (OR = 5.082, 95% CI: 2.224–11.612), engagement in multi-person sexual behavior (OR = 2.186, 95% CI: 1.236–3.867), and substance use (OR = 1.908, 95% CI: 1.167–3.118). Furtherly, students with higher adherence to PrEP were likely to have receptive sexual behaviors (OR = 8.702, 95% CI: 2.070-36.592), absence of substance use (OR = 4.468, 95% CI: 1.371–14.561), and uptake of PrEP through daily oral route. (OR = 7.065, 95% CI: 1.699–29.371). Conclusion: YMSM students exhibit distinct patterns of "high awareness, low willingness, low uptake, and low adherence" to PrEP. Strategies for reduction in the acquisition of HIV prioritizing the current features of utilizing PrEP were urgently warranted. [ABSTRACT FROM AUTHOR]

Objectives: To investigate prognostic-related gene signature based on DNA damage repair and tumor microenvironment statue in human papillomavirus 16 negative (HPV16-) head and neck squamous cell carcinoma (HNSCC). Methods: For the RNA-sequence matrix in HPV16- HNSCC in the Cancer Genome Atlas (TCGA) cohort, the DNA damage response (DDR) and tumor microenvironment (TM) status of each patient sample was estimated by using the ssGSEA algorithm. Through bioinformatics analysis in DDR_high/TM_high (n = 311) and DDR_high/TM_low (n = 53) groups, a survival-related gene signature was selected in the TCGA cohort. Two independent external validation cohorts (GSE65858 (n = 210) and GSE41613 (n = 97)) with HPV16- HNSCC patients validated the gene signature. Correlations among the clinical-related hub differentially expressed genes (DEGs) and infiltrated immunocytes were explored with the TIMER2.0 server. Drug screening based on hub DEGs was performed using the CellMiner and GSCALite databases. The loss-of-function studies were used to evaluate the effect of screened survival-related gene on the motility of HPV- HNSCC cells in vitro. Results: A high DDR level (P = 0.025) and low TM score (P = 0.012) were independent risk factors for HPV16- HNSCC. Downregulated expression of ALOX12B or SPRR1A was associated with poor survival rate and advanced cancer stages. The pathway enrichment analysis showed the DDR_high/TM_low samples were enriched in glycosphingolipid biosynthesis-lacto and neolacto series, glutathione metabolism, platinum drug resistance, and ferroptosis pathways, while the DDR_high/TM_low samples were enriched in Th17 cell differentiation, Neutrophil extracellular trap formation, PD − L1 expression and PD − 1 checkpoint pathway in cancer. Notably, the expression of ALOX12B and SPRR1A were negatively correlated with cancer-associated fibroblasts (CAFs) infiltration and CAFs downstream effectors. Sensitivity to specific chemotherapy regimens can be derived from gene expressions. In addition, ALOX12B and SPRR1A expression was associated with the mRNA expression of insulin like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), mammalian target of rapamycin (MTOR), and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) in HPV negative HNSCC. Down-regulation of ALOX12B promoted HPV- HNSCC cells migration and invasion in vitro. Conclusions: ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs. The specific drug pattern was determined by the gene signature. [ABSTRACT FROM AUTHOR]

Objectives: To investigate prognostic-related gene signature based on DNA damage repair and tumor microenvironment statue in human papillomavirus 16 negative (HPV16-) head and neck squamous cell carcinoma (HNSCC).Methods: For the RNA-sequence matrix in HPV16- HNSCC in the Cancer Genome Atlas (TCGA) cohort, the DNA damage response (DDR) and tumor microenvironment (TM) status of each patient sample was estimated by using the ssGSEA algorithm. Through bioinformatics analysis in DDR_high/TM_high (n = 311) and DDR_high/TM_low (n = 53) groups, a survival-related gene signature was selected in the TCGA cohort. Two independent external validation cohorts (GSE65858 (n = 210) and GSE41613 (n = 97)) with HPV16- HNSCC patients validated the gene signature. Correlations among the clinical-related hub differentially expressed genes (DEGs) and infiltrated immunocytes were explored with the TIMER2.0 server. Drug screening based on hub DEGs was performed using the CellMiner and GSCALite databases. The loss-of-function studies were used to evaluate the effect of screened survival-related gene on the motility of HPV- HNSCC cells in vitro.Results: A high DDR level (P = 0.025) and low TM score (P = 0.012) were independent risk factors for HPV16- HNSCC. Downregulated expression of ALOX12B or SPRR1A was associated with poor survival rate and advanced cancer stages. The pathway enrichment analysis showed the DDR_high/TM_low samples were enriched in glycosphingolipid biosynthesis-lacto and neolacto series, glutathione metabolism, platinum drug resistance, and ferroptosis pathways, while the DDR_high/TM_low samples were enriched in Th17 cell differentiation, Neutrophil extracellular trap formation, PD - L1 expression and PD - 1 checkpoint pathway in cancer. Notably, the expression of ALOX12B and SPRR1A were negatively correlated with cancer-associated fibroblasts (CAFs) infiltration and CAFs downstream effectors. Sensitivity to specific chemotherapy regimens can be derived from gene expressions. In addition, ALOX12B and SPRR1A expression was associated with the mRNA expression of insulin like growth factor 1 receptor (IGF1R), AKT serine/threonine kinase 1 (AKT1), mammalian target of rapamycin (MTOR), and eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) in HPV negative HNSCC. Down-regulation of ALOX12B promoted HPV- HNSCC cells migration and invasion in vitro.Conclusions: ALOX12B and SPRR1A served as a gene signature for overall survival in HPV16- HNSCC patients, and correlated with the amount of infiltrated CAFs. The specific drug pattern was determined by the gene signature. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord. Methods: To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin–eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord. Result: M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination. Conclusion: Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option. [ABSTRACT FROM AUTHOR]

Background and aims: Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. Methods: A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. Results: Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-β1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-β1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. Conclusions: Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-β1 and restoration of intra-renal autophagy. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. Materials and methods: A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). Results: We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46–1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82–2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4–1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. Conclusion: DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a severe neurological disorder that causes neurological impairment and disability. Neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) represent a promising cell therapy strategy for spinal cord regeneration and repair. However, iPSC-derived NS/PCs face many challenges and issues in SCI therapy; one of the most significant challenges is epigenetic regulation and that factors that influence this mechanism. Epigenetics refers to the regulation of gene expression and function by DNA methylation, histone modification, and chromatin structure without changing the DNA sequence. Previous research has shown that epigenetics plays a crucial role in the generation, differentiation, and transplantation of iPSCs, and can influence the quality, safety, and outcome of transplanted cells. In this study, we review the effects of epigenetic regulation and various influencing factors on the role of iPSC-derived NS/PCs in SCI therapy at multiple levels, including epigenetic reprogramming, regulation, and the adaptation of iPSCs during generation, differentiation, and transplantation, as well as the impact of other therapeutic tools (e.g., drugs, electrical stimulation, and scaffolds) on the epigenetic status of transplanted cells. We summarize our main findings and insights in this field and identify future challenges and directions that need to be addressed and explored. [ABSTRACT FROM AUTHOR]

Background: Lowering the exit position of the tibial tunnel can improve the clinical efficacy of posterior cruciate ligament (PCL) reconstruction, however, there is no unified positioning standard. This study aimed to use novel soft tissue landmarks to create a low tunnel. Methods: A total of 14 human cadaveric knees and 12 patients with PCL injury were included in this study. Firstly, we observed the anatomical position between the PCL, posterior septum, and other tissue, and evaluated the relationship between the center of the low tibial tunnel (SP tunnel) and posterior septum and distal reflection of posterior capsule, and using computed tomography (CT) to evaluate distance between the center of the SP tunnel with bony landmarks. Then, evaluated the blood vessels content in the posterior septum with HE staining. Finally, observed the posterior septum and distal reflection of the posterior capsule under arthroscopy to explore the clinical feasibility of creating a low tibial tunnel, and assessed the risk of surgery by using ultrasound to detect the distance between the popliteal artery and the posterior edge of tibial plateau bone cortex. Results: In all 14 cadaveric specimens, the PCL tibial insertions were located completely within the posterior medial compartment of the knee. The distance between the center of the SP tunnel and the the articular surface of tibial plateau was 9.4 ± 0.4 mm. All SP tunnels retained an intact posterior wall, which was 1.6 ± 0.3 mm from the distal reflection of the posterior capsule. The distances between the center of the SP tunnel and the the articular surface of tibial plateau, the champagne glass drop-off were 9.2 ± 0.4 mm (ICC: 0.932, 95%CI 0.806–0.978) and 1.5 ± 0.2 mm (ICC:0.925, 95%CI 0.788–0.975) in CT image. Compared with the posterior capsule, the posterior septum contained more vascular structures. Last, all 12 patients successfully established low tibial tunnels under arthroscopy, and the distance between the posterior edge of tibial plateau bone cortex and the popliteal artery was 7.8 ± 0.3, 9.4 ± 0.4 and 7.4 ± 0.3 mm at 30°, 60° and 90° flexion angels after filling with water and supporting with shaver in posterior-medial compartment of knee joint. Conclusions: A modified low tibial tunnel could be established in the PCL anatomical footprint by using the posterior septum and posterior capsule as landmarks. [ABSTRACT FROM AUTHOR]

Background: Hybridization is a useful strategy to produce offspring with more desirable phenotypic characteristics than those of parents. The hybrid grouper derived from the cross of Cromileptes altivelis (♀, 2n = 48) with Epinephelus lanceolatus (♂, 2n = 48) exhibits improved growth compared with its female parent, which makes it valuable to aquaculture. However, the genetic traits of the hybrid grouper are poorly understood. Results: The observations showed that the hybrid grouper was diploid (2n = 48) and displayed intermediate morphology with the parent's measurable characteristics. The ribosomal DNA (rDNA) and mitochondria DNA (mtDNA) were characterized at molecular and phylogenetic level. High similarity and low genetic distance of 5S rDNA and mtDNA sequences between the hybrid grouper and C. altivelis showed that the hybrid grouper had a closer genetic relationship with female parents. The reconstructed phylogenetic tree based on COI gene and D-loop region of mtDNA recovered that mtDNA was maternally inherited in the hybrid grouper. Additionally, the DNA methylation level of 5S rDNA intergenic spacers (IGS) sequence was tested in here. The results showed that the DNA methylation status of the hybrid grouper was significantly lower than that of C. altivelis. Conclusion: Results of this study provide important data on the genetic characteristics of the hybrid derived from the cross of C. altivelis and E. lanceolatus, and contribute the knowledge of both evolution and marine fish breeding. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear. Methods: We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets. Results: Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential. Conclusion: Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development. [ABSTRACT FROM AUTHOR]

Objectives: Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model. Methods: BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-ExosmiRNA−210 mimic and BMSC-ExosmiRNA−210 inhibitor secreted from such cells were collected. The differences between BMSC-Exos, BMSC-ExosmiRNA−210 mimic and BMSC-ExosmiRNA−210 inhibitor in protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague–Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-ExosmiRNA−210 mimic or BMSC-ExosmiRNA−210 inhibitor were conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model. Results: Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-ExosmiRNA−210 mimic could further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-ExosmiRNA−210 inhibitor group showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-ExosmiRNA−210 mimic, could increase microvascular density and enhance bone remodeling of femoral heads. Conclusions: BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH. [ABSTRACT FROM AUTHOR]

Background: The relationship between lean body mass (LBM) and blood pressure (BP) is controversial and limited. This study investigated the associations between LBM indexes and BP in adults of different ages and with varying body fat distribution. Methods: The data for the present analysis was obtained from a cross-sectional survey of 1,465 adults (50.7% males) aged 18–70 years conducted in Beijing, China. Regional LBM and fat distribution, including fat mass (FM) and android to gynoid fat ratio (AOI), were assessed using a dual-energy X-ray bone densitometer. Generalized Liner Model (GLM) was employed. Confounders, including age, sex, height, weight, smoking, and alcohol use, were evaluated through questionnaires and physical examinations. Results: Males had higher rates of hypertension (11.19% vs. 4.92%) and prehypertension (21.57% vs. 14.59%) than females. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 122.04 mmHg and 76.68 mmHg. There were no significant associations between LBM and DBP (p > 0.05). However, arms LBM (β = 1.86, 95% CI: 0.77, 2.94) and trunk LBM (β = 0.37, 95% CI: 0.01, 0.73) were significantly associated with SBP. The association of LBM on DBP was stronger with increasing ages, and stronger in females than in males (p < 0.001). The association between adults' arms LBM and SBP was stronger in the high level FM group (β = 2.74 vs. β = 1.30) and high level AOI group (β = 1.80 vs. β = 2.08). Conclusion: The influence of LBM on SBP increases with age, particularly after the age twenty years in females. For adults with high FM or high AOI, LBM in the arms, showed a stronger positive predictive association with SBP. This suggests that, in addition to controlling fat content, future efforts to improve cardiovascular health in adults should include the management of LBM (especially in the upper body). [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a major and common cause of suicide. The purpose of this article is to report the clinical characteristics and patterns of co-morbid suicidal behavior (SB) in first hospitalized and drug-naïve MDD patients. Methods: A total of 345 patients with first hospitalization and drug-naïve MDD with SB were included in this study, while 183 patients without SB were included as a control group. We collected socio-demographic, general clinical data and common biochemical indicators of all participants and assessed their clinical symptoms. Results: Compared to patients without SB, MDD with SB had more severe clinical symptoms and worse metabolic indicators. Duration of disease, depressive symptom scores, and thyroid stimulating hormone (TSH) levels was risk factors for SB and its number. Conclusions: MDD patients with SB suffered more severe clinical symptoms and worse metabolic indicators, and risk factors for SB in this population were identified, which may provide beneficial insight and reference for clinical prevention and intervention of SB in MDD patients. [ABSTRACT FROM AUTHOR]

Background: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. Methods: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. Results: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). Conclusions: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients. [ABSTRACT FROM AUTHOR]

Purpose: To report the planning benchmark case results of the POTENTIAL trial—a multicenter, randomized, phase 3 trial—to evaluate the value of internal mammary nodal (IMN) irradiation for patients with high-risk breast cancer. Methods: All participating institutions were provided the outlines of one benchmark case, and they generated radiation therapy plans per protocol. The plans were evaluated by a quality assurance team, after which the institutions resubmitted their revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed in the first and final submission. Results: The plans from 26 institutions were analyzed. Some major deviations were found in the first submission. The protocol compliance rates of dose coverage for the planning target volume of chest wall, supraclavicular fossa plus axilla, and IMN region (PTVim) were all significantly improved in the final submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8%, respectively. For OARs, the compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. In the first and final submission, the mean values of PTVim V100% were 79.9% vs. 92.7%; the mean values of heart Dmean were 11.5 Gy vs. 9.7 Gy for hypofractionated radiation therapy and 11.5 Gy vs. 11.0 Gy for conventional fractionated radiation therapy, respectively. Conclusion: The major deviations were corrected and protocol compliance was significantly improved after revision, which highlighted the importance of planning benchmark case to guarantee the planning quality for multicenter trials. [ABSTRACT FROM AUTHOR]

Background: Phthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity. Methods: A total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children's Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity. Results: Overall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (β = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (β = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (β = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P < 0.05), and most of the PAE metabolites exposures showed risk ratios > 1 for their femininity. Conclusion: Long-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested the potential association between air pollution and tuberculosis incidence, but this association remains inconclusive and evidence to assess causality is particularly lacking. We aimed to draw causal inference between fine particulate matter less than 2.5 μm in diameter (PM2.5) and tuberculosis in China. Methods: Granger causality (GC) inference was performed within vector autoregressive models at levels and/or first-differences using annual national aggregated data during 1982–2019, annual provincial aggregated data during 1982–2019 and monthly provincial aggregated data during 2004–2018. Convergent cross-mapping (CCM) approach was used to determine the backbone nonlinear causal association based on the monthly provincial aggregated data during 2004–2018. Moreover, distributed lag nonlinear model (DLNM) was applied to quantify the causal effects. Results: GC tests identified PM2.5 driving tuberculosis dynamics at national and provincial levels in Granger sense. Empirical dynamic modeling provided the CCM causal intensity of PM2.5 effect on tuberculosis at provincial level and demonstrated that PM2.5 had a positive effect on tuberculosis incidence. Then, DLNM estimation demonstrated that the PM2.5 exposure driven tuberculosis risk was concentration- and time-dependent in a nonlinear manner. This result still held in the multi-pollutant model. Conclusions: Causal inference showed that PM2.5 exposure driving tuberculosis, which showing a concentration gradient change. Air pollutant control may have potential public health benefit of decreasing tuberculosis burden. [ABSTRACT FROM AUTHOR]

Background: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. Methods: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. Discussion: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. Trial registration: ChiCTR2300069998. Registered on 30 March 2023. [ABSTRACT FROM AUTHOR]

Background: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. Case presentation: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. Conclusion: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis. [ABSTRACT FROM AUTHOR]

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors. [ABSTRACT FROM AUTHOR]

With the invasion of green tides and the increase of urban green areas worldwide, multimillion tons of Enteromorpha need to be reutilized. In this study, Enteromorpha prolifera powder is considered a promising biomass resource for the production of commercial chemical products production. Ilamycins, novel cyclic heptapeptides with significant anti-TB activities, are isolated from Streptomyces atratus SCSIO ZH16, a deep-sea-derived strain. Using EP powder as a nitrogen source, the production of ilamycins reached 709.97 mg/L through optimization of the nitrogen source using the engineered strain S. atratus SCSIO ZH16 ΔR. After mutant strain constructions and tests, strain S. atratus SCSIO ZH16 ΔR::bldD EP powder achieved a higher production titer of ilamycins. Furthermore, the production titer of ilamycins and ilamycin E reached 1561.77 mg/L and 745.44 mg/L, respectively, in a 5 L bioreactor. This study suggests that E. prolifera is a promising and eco-friendly nitrogen source for the production of ilamycins. [ABSTRACT FROM AUTHOR]

Background: The protozoan parasite Toxoplasma gondii infects and alters the neurotransmission in cerebral cortex and other brain regions, leading to neurobehavioral and neuropathologic changes in humans and animals. However, the molecules that contribute to these changes remain largely unknown. Methods: We have investigated the impact of T. gondii infection on the overall metabolism of mouse cerebral cortex. Mass-spectrometry-based metabolomics and multivariate statistical analysis were employed to discover metabolomic signatures that discriminate between cerebral cortex of T. gondii-infected and uninfected control mice. Results: Our results identified 73, 67 and 276 differentially abundant metabolites, which were involved in 25, 37 and 64 pathways at 7, 14 and 21 days post-infection (dpi), respectively. Metabolites in the unsaturated fatty acid biosynthesis pathway were upregulated as the infection progressed, indicating that T. gondii induces the biosynthesis of unsaturated fatty acids to promote its own growth and survival. Some of the downregulated metabolites were related to pathways, such as steroid hormone biosynthesis and arachidonic acid metabolism. Nine metabolites were identified as T. gondii responsive metabolites, namely galactosylsphingosine, arachidonic acid, LysoSM(d18:1), l-palmitoylcarnitine, calcitetrol, 27-Deoxy-5b-cyprinol, l-homophenylalanine, oleic acid and ceramide (d18:1/16:0). Conclusions: Our data provide novel insight into the dysregulation of the metabolism of the mouse cerebral cortex during T. gondii infection and have important implications for studies of T. gondii pathogenesis. [ABSTRACT FROM AUTHOR]

Backgroud: Early diagnosis of gastric tuberculosis is often challenging because the disease is very rare and its clinical manifestation is nonspecific and misleading. To raise the awareness and emphasize early diagnosis of gastric tuberculosis, we present a case of gastric tuberculosis secondary to pleural and pulmonary tuberculosis.Case Presentation: A 26-year-old woman complained gastric pain for 1 month but showed no other symptoms, who had no previous exposure to tuberculosis.Gastric stromal tumor was originally suspected. However, the pathology of her gastroscopic biopsy of the gastric lesion showed granulomatous lesions and caseating necrosis. Gene sequencing of the biopsy specimen identified deoxyribonucleic acid fragment of Mycobacterium tuberculosis. Chest computed tomography scan revealed nodular shadows in the lesser curvature soft tissue of the stomach, patchy densities and calcified nodular shadows in the upper right lung, bilateral pleural thickening, and calcified pleural nodules. Thus, the diagnosis was gastric tuberculosis secondary to pulmonary and pleural tuberculosis. The patient was hospitalized and treated with the antituberculosis therapy for 1 week. After discharged from the hospital, the patient continued routine antituberculosis therapy for 18 months and was follow-up was normal.Literature search found 22 cases of gastric tuberculosis reported from 2000 to 2016. Review of the 22 cases suggested that polymerase chain reaction has been increasingly used in the recent years in addition to the conventional histopathological and bacteriological approaches.Conclusion: Clinical presentation of gastric tuberculosis is not specific.When granuloma or caseation is detected on biopsy in patients who are suspected of having gastric malignancy or acid peptic diseases, polymerase chain reaction for Mycobacterium tuberculosis could be used as an available and sensitive diagnostic test in addition to pathology, acid-fast bacilli smear staining and culture. [ABSTRACT FROM AUTHOR]

Background: We sought to determine (1) whether the addition of prophylactic oral mosapride to a protocol including dexamethasone and ondansetron further reduces postoperative nausea and vomiting (PONV) compared with ondansetron alone or the combination of both; (2) whether preemptive application of oral mosapride provides additional clinical benefits for bowel function and appetite, thus improving functional recovery. Methods: We randomized 240 patients undergoing total hip and knee arthroplasty to receive placebo (Control, n = 80), dexamethasone (10 mg) before anesthesia induction (Dexa, n = 82), or dexamethasone (10 mg) before anesthesia induction as well as oral mosapride (5 mg) before and after surgery (Mosa+Dexa, n = 78). Patients were assessed at 0–6, 6–12, 12–24, and 24–48 h postoperatively. Primary outcomes were incidence and severity of PONV as well as complete response. Secondary outcomes were appetite, time until first defecation and ambulation, patient satisfaction score, and length of hospital stay. Results: Mosa+Dexa patients showed significantly lower incidence of nausea at 6–12 h (3.8%) and over the entire evaluation period (6.4%), as well as a higher rate of complete response (89.7%) than other patients. Mosa+Dexa patients required less time to achieve first defecation and ambulation, they were hospitalized for shorter time, and they were more satisfied with clinical care. Conclusion: Addition of oral mosapride further reduced incidence of PONV, especially postoperative nausea, during 6–12 h postoperatively. Moreover, preemptive application of oral mosapride can further improve appetite, bowel function, ambulation and length of hospital stay. Trial registration: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896), prospectively registered on 27/04/2018. [ABSTRACT FROM AUTHOR]