Genotype-phenotype correlation and founder effect analysis in southeast Chinese patients with sialidosis type I.

BACKGROUND: Sialidosis type 1 (ST-1) is a rare autosomal recessive disorder caused by mutation in the NEU1 gene. However, limited reports on ST-1 patients in the Chinese mainland are available. METHODS: This study reported the genetic and clinical characteristics of 10 ST-1 patients from southeastern China. A haplotype analysis was performed using 21 single nucleotide polymorphism (SNP) markers of 500 kb flanking the recurrent c.544 A > G in 8 families harboring the mutation. Furthermore, this study summarized and compared previously reported ST-1 patients from Taiwan and mainland China. RESULTS: Five mutations within NEU1 were found, including two novel ones c.557 A > G and c.799 C > T. The c.544 A > G mutation was most frequent and identified in 9 patients, 6 patients were homozygous for c.544 A > G. Haplotype analysis revealed a shared haplotype surrounding c.544 A > G was identified, suggesting a founder effect presenting in southeast Chinese population. Through detailed assessment, 52 ST-1 patients from 45 families from Taiwan and mainland China were included. Homozygous c.544 A > G was the most common genotype and found in 42.2% of the families, followed by the c.544 A > G/c.239 C > T compound genotype, which was observed in 22.2% of the families. ST-1 patients with the homozygous c.544 A > G mutation developed the disease at a later age and had a lower incidence of cherry-red spots significantly. CONCLUSION: The results contribute to gaps in the clinical and genetic features of ST-1 patients in southeastern mainland China and provide a deeper understanding of this disease to reduce misdiagnosis.

Clinical characterization and founder effect analysis in Chinese amyotrophic lateral sclerosis patients with SOD1 common variants.

OBJECTIVE: In the Asian population, SOD1 variants are the most common cause of amyotrophic lateral sclerosis (ALS). To date, more than 200 variants have been reported in SOD1. This study aimed to summarize the genotype-phenotype correlation and determine whether the patients carrying common variants derive from a common ancestor. METHODS: A total of 103 sporadic ALS (SALS) and 11 familial ALS (FALS) probands were included and variants were screened by whole exome sequencing. Functional analyses were performed on fibroblasts derived from patients with SOD1 p.V48A and control. Haplotype analysis was performed in the probands with p.H47R or p.V48A and their familial members. RESULTS: A total of 25 SOD1 variants were identified in 44 probands, in which p.H47R, p.V48A and p.C112Y variants were the most common variants. 94.3% and 60% of patients with p.H47R or p.V48A had lower limb onset with predominant lower motor neurons (LMNs) involvement. Patients with p.H47R had a slow progression and prolonged survival time, while patients with p.V48A exhibited a duration of 2-5 years. Patients with p.C112Y variant showed remarkable phenotypic variation in age at onset and disease course. SOD1V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast. Haplotype analysis showed that seven families had two different haplotypes. p.H47R and p.V48A variants did not originate from a common founder. CONCLUSIONS: Our study expanded the understanding of the genotype-phenotype correlation of ALS with SOD1 variants and revealed that the common p.H47R or p.V48A variant did not have a founder effect.

In our ALS cohort, 44 ALS probands were identified with 25 SOD1 variants, of which p.H47R, p.V48A and p.C112Y variants were the most frequent. The genotype­phenotype relationship of patients with SOD1 p.H47R, p.V48A and p.C112Y patients were summarized.SOD1^V48A fibroblasts showed mutant SOD1 aggregate formation, enhanced intracellular reactive oxygen species level, and decreased mitochondrial membrane potential compared to the control fibroblast.Our study expanded the understanding of the genotype­phenotype correlation of ALS with SOD1 variants and showed the common variants p.H47R or p.V48A did not have a founder effect.

Association of hemoglobin glycation index with clinical outcomes in patients with coronary artery disease: a prospective cohort study.

BACKGROUND: To analyze the association between the hemoglobin glycation index (HGI) and the long-term prognosis of patients with coronary artery disease (CAD). METHODS: HGI represented the difference between laboratory measured Hemoglobin A1c (HbA1c) and predicted HbA1c based on a liner regression between Hb1Ac and fasting plasma glucose (FPG). A total of 10 598 patients who treated with percutaneous coronary intervention (PCI) were stratified into three groups (low HGI group: HGI<-0.506, medium HGI group: -0.506 ≤ HGI < 0.179, and high HGI group: HGI ≥ 0.179). The primary endpoints includes all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: A total of 321 ACMs, 243 CMs, 774 MACEs, and 854 MACCEs were recorded during a 60-month follow-up period. After adjusting for confounders using a multivariate Cox regression analysis, the patients in the low HGI group had a significantly increased risk of ACM (adjusted HR = 1.683, 95%CI:1.179-2.404, P = 0.004) and CM (HR = 1.604, 95%CI:1.064-2.417, P = 0.024) as compared with patients in the medium HGI group. Similarly, the patients in the high HGI group had an increased risk of MACEs (HR = 1.247, 95% CI: 1.023-1.521, P = 0.029) as compared with patients in the medium HGI group. For ACM, CM, and MACEs, a U-shaped relation were found among these three groups. However, we did not find significant differences in the incidence of MACCEs among these three groups. CONCLUSION: The present study indicates that HGI could be an independent predictor for the risk of mortality and MACEs in patients with CAD.

F13B regulates angiogenesis and tumor progression in hepatocellular carcinoma via the HIF-1α/VEGF pathway.

Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor with a poor prognosis. This research aimed to investigate the role of F13B in HCC and its underlying mechanisms. Through comprehensive bioinformatics analysis of the GSE120123 and The Cancer Genome Atlas (TCGA)-Liver hepatocellular carcinoma (LIHC) datasets, we identified 220 overlapping prognosis-related genes. Eight key genes, including the previously unreported CCDC170 and F13B in HCC, were identified through Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis. F13B emerged as a significant prognostic factor in HCC, warranting further investigation in subsequent analyses. In vitro experiments showed that F13B expression was notably reduced in HCC cell lines and tissues, particularly in Huh-7 and SMMC-7721 cells. Overexpression of F13B inhibited cell invasion, migration, and proliferation, while its knockdown produced the opposite effect. A lactate dehydrogenase (LDH) activity assay in human umbilical vein endothelial cells (HUVECs) demonstrated that F13B overexpression reduced vascular endothelial growth factor (VEGF)-induced cytotoxicity, whereas knockdown increased it. Further analysis revealed that F13B negatively regulates VEGFA expression, affecting HUVEC proliferation. In HUVECs, F13B overexpression reversed VEGF-induced upregulation of key angiogenesis markers, including phospho-VEGF receptor 2 (p-VEGFR2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), as well as AKT/mTOR signaling proteins, phospho-Akt (p-AKT), and phospho-mTOR (p-mTOR). Additionally, F13B negatively regulated VEGFA and hypoxia-inducible factor 1 A (HIF1A) under hypoxic conditions, counteracting the hypoxia-induced increase in cell viability. These findings suggest that F13B regulates angiogenesis through the HIF-1α/VEGF pathway and plays a crucial role in HCC progression. Our results highlight the potential of F13B as a therapeutic target in HCC, providing novel insights into the molecular mechanisms of HCC and its prognostic significance.

Designing Zero-Dimensional Cadmium-Based Organic-Inorganic Hybrids: The Role of Halogen Doping in Modulating Multifunctional Properties.

Advances in materials science are increasingly dependent on the development of multifunctional materials capable of improving system efficiency and reducing the environmental impact. In this study, two zero-dimensional (0D) cadmium-based organic-inorganic hybrid materials (BEMPD)2CdBr4 (BEMPD-Br, 1) and (BEMPD)2CdBr2Cl2 (BEMPD-ClBr, 2) (BEMPD = 1-(2-bromoethyl)-1-methylpiperidine) were prepared by halogen doping. Compound 2 is a mixed halide in which there are two halogen sites, Cl and Br, and in a disordered state, which has a regulatory effect on the structural distortion and properties of the compound. The Curie temperatures of compounds 1 and 2 are 348 and 390 K, respectively, and the UV-vis absorption spectra showed that the direct band gaps of compounds 1 and 2 were 4.68 and 4.8 eV, respectively. In addition, room-temperature photoluminescence experiments show broadband emission peaks at 717 and 683 nm for compounds 1 and 2, respectively, with fluorescence lifetimes of 2.414 and 3.915 µs. These 0D hybrids provide an avenue for the development of smart materials and optoelectronic devices, and also provide positive clues for manipulating the properties of organic-inorganic hybrid compounds.

The prevalence of 12-month suicidal ideation and associated factors among university students in China: Findings from a three-wave cross-sectional study from 2021 to 2023.

BACKGROUND: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China. METHODS: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation. RESULTS: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation. LIMITATIONS: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students. CONCLUSIONS: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population.

CRISPR/Gal4BD-Cas donor adapting systems based on miniaturized Cas proteins for improved gene editing.

Targeted precise point editing and knock-in can be achieved by homology-directed repair(HDR) based gene editing strategies in mammalian cells. However, the inefficiency of HDR strategies seriously restricts their application in precision medicine and molecular design breeding. In view of the problem that exogenous donor DNA cannot be efficiently recruited autonomously at double-stranded breaks(DSBs) when using HDR strategies for gene editing, the concept of donor adapting system(DAS) was proposed and the CRISPR/Cas9-Gal4BD DAS was developed previously. Due to the large size of SpCas9 protein, its fusion with the Gal4BD adaptor is inconvenient for protein expression, virus vector packaging and in vivo delivery. In this study, two novel CRISPR/Gal4BD-SlugCas9 and CRISPR/Gal4BD-AsCas12a DASs were further developed, using two miniaturized Cas proteins, namely SlugCas9-HF derived from Staphylococcus lugdunensis and AsCas12a derived from Acidaminococcus sp. Firstly, the SSA reporter assay was used to assess the targeting activity of different Cas-Gal4BD fusions, and the results showed that the fusion of Gal4BD with SlugCas9 and AsCas12a N-terminals had minimal distraction on their activities. Secondly, the HDR efficiency reporter assay was conducted for the functional verification of the two DASs and the corresponding donor patterns were optimized simultaneously. The results demonstrated that the fusion of the Gal4BD adaptor binding sequence at the 5'-end of intent dsDNA template (BS-dsDNA) was better for the CRISPR/Gal4BD-AsCas12a DAS, while for the CRISPR/Gal4BD-SlugCas9 DAS, the dsDNA-BS donor pattern was recommended. Finally, CRISPR/Gal4BD-SlugCas9 DAS was used to achieve gene editing efficiency of 24%, 37% and 31% respectively for EMX1, NUDT5 and AAVS1 gene loci in HEK293T cells, which was significantly increased compared with the controls. In conclusion, this study provides a reference for the subsequent optimization of the donor adapting systems, and expands the gene editing technical toolbox for the researches on animal molecular design breeding.

Hybrids of 3-Hydroxypyridin-4(1H)-ones and Long-Chain 4-Aminoquinolines as Potent Biofilm Inhibitors of Pseudomonas aeruginosa Potentiate Tobramycin and Polymyxin B Activity.

The biofilm formation of Pseudomonas aeruginosa involves multiple complex regulatory pathways; thus, blocking a single pathway is unlikely to achieve the desired antibiofilm efficacy. Herein, a series of hybrids of 3-hydroxypyridin-4(1H)-ones and long-chain 4-aminoquinolines were synthesized as biofilm inhibitors against P. aeruginosa based on a multipathway antibiofilm strategy. Comprehensive structure-activity relationship studies identified compound 30b as the most valuable antagonist, which significantly inhibited P. aeruginosa biofilm formation (IC50 = 5.8 µM) and various virulence phenotypes. Mechanistic studies revealed that 30b not only targets the three quorum sensing systems but also strongly induces iron deficiency signals in P. aeruginosa. Furthermore, 30b demonstrated a favorable in vitro and in vivo safety profile. Moreover, 30b specifically enhanced the antibacterial activity of tobramycin and polymyxin B in in vitro and in vivo combination therapy. Overall, these results highlight the potential of 30b as a novel anti-infective candidate for treating P. aeruginosa infections.

The Fluorinated NAD Precursors Enhance FK866 Cytotoxicity by Activating SARM1 in Glioblastoma Cells.

Glioblastoma, a formidable brain tumor characterized by dysregulated NAD metabolism, poses a significant therapeutic challenge. The NAMPT inhibitor FK866, which induces NAD depletion, has shown promise in controlling tumor proliferation and modifying the tumor microenvironment. However, the clinical efficacy of FK866 as a single drug therapy for glioma is limited. In this study, we aim to disrupt NAD metabolism using fluorinated NAD precursors and explore their synergistic effect with FK866 in inducing cytotoxicity in glioblastoma cells. The synthesized analogue of nicotinamide riboside (NR), ara-F nicotinamide riboside (F-NR), inhibits nicotinamide ribose kinase (NRK) activity in vitro, reduces cellular NAD levels, and enhances FK866's cytotoxicity in U251 glioblastoma cells, indicating a collaborative impact on cell death. Metabolic analyses reveal that F-NR undergoes conversion to fluorinated nicotinamide mononucleotide (F-NMN) and other metabolites, highlighting the intact NAD metabolic pathway in glioma cells. The activation of SARM1 by F-NMN, a potent NAD-consuming enzyme, is supported by the synergistic effect of CZ-48, a cell-permeable SARM1 activator. Temporal analysis underscores the sequential nature of events, establishing NAD depletion as a precursor to ATP depletion and eventual massive cell death. This study not only elucidates the molecular intricacies of glioblastoma cell death but also proposes a promising strategy to enhance FK866 efficacy through fluorinated NAD precursors, offering potential avenues for innovative therapeutic interventions in the challenging landscape of glioblastoma treatment.

Advantages of metagenomic next-generation sequencing in the management of ANCA-associated vasculitis patients with suspected pulmonary infection as a rule-out tool.

OBJECTIVE: Pulmonary infection is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). It is sometimes difficult to differentiate pulmonary infection from pulmonary involvement of vasculitis in AAV patients. Fiberoptic bronchoscopy and bronchoalveolar lavage fluid (BALF) assays are useful diagnostic methods. In addition to conventional microbiological tests (CMTs), metagenomic next-generation sequencing (mNGS) facilitates rapid and sensitive detection of various pathogens. The current study aimed to evaluate the advantages of additional BALF mNGS in the management of pulmonary infection in AAV patients. METHODS: 27 patients with active AAV and suspected pulmonary infection whose BALF samples were tested by mNGS and CMTs and 17 active AAV patients whose BALF were tested by CMTs alone were retrospectively recruited. The results of microbiological tests, and adjustments of treatment following BALF mNGS, were described. The durations of antimicrobial treatment and in-hospital mortality in patients were compared. RESULTS: Among the 27 patients whose BALF samples were tested by mNGS, 25.9% of patients did not have evidence of pathogenic microorganism in their BALF samples, 55.6% had polymicrobial infections, including bacteria, fungi and viruses. Of these 27 patients, 40.7% did not have evidence of pathogenic microorganism in their BALF or serum samples according to CMTs. Patients in the BALF mNGS/CMT group received a significantly shorter duration of antibacterial and total antimicrobial treatment than patients in the CMT alone group (17.3 ± 14.7 vs. 27.9 ± 19.0 days, P = 0.044; 18.9 ± 15.0 vs. 29.5 ± 17.7 days, P = 0.040, respectively). Fewer patients in the BALF mNGS/CMT group died than in the CMT alone group (4/27 vs. 7/17, P = 0.049). CONCLUSION: Compared with CMT alone, additional mNGS tests may shorten the duration of antimicrobial treatment and possibly decrease death from severe infection by providing precise and quick diagnosis of infection.

Effect of Cyclic Warm-Rolling Technique on Mechanical Properties of MoCu30 Thin Plates with Heterogeneous Structure.

By employing a cyclic warm rolling technique, MoCu30 alloy sheets of different thicknesses were prepared to investigate the effects of various rolling reduction rates on the microstructure and mechanical properties of MoCu30 alloys. Additionally, the evolution of microscale heterogeneous deformation during the tensile process was observed based on DIC technology. This study reveals that Mo-Cu interfaces at different deformation rates exhibit an amorphous interlayer of 0.5-1.0 µm thickness, which contributes to enhancing the bond strength of Mo-Cu interfaces. As the rolling reduction rate increased, the grain size of the MoCu30 alloy gradually decreased, whereas the dislocation density and hardness increased. Furthermore, the yield strength and tensile strength of the MoCu30 alloy increased gradually, whereas the elongation decreased. At a deformation rate of 74% (2 mm), the yield strength, tensile strength, and elongation of the MoCu30 alloy were 647.9 MPa, 781.8 MPa, and 11.7%, respectively. During the tensile process of Mo-Cu dual-phase heterogeneous material, a unique hierarchical strain banding was formed, which helps to suppress strain localization and prevent premature plastic instability.

Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study.

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (ß: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.

Melatonin mitigates cadmium toxicity by promoting root development, delaying root senescence, and regulating cadmium transport in cotton.

Cd ions are absorbed and transported from the soil by crop roots, which are the first organ to be exposed to Cd. This results in an increase in cadmium ions in crops, significantly affecting crop growth and yield. Exogenous melatonin (MT) can help reduce cadmium (Cd) stress in cotton, but the specific contribution of roots to this process remains unclear. In order to address this knowledge gap, an in-situ root phenotyping study was conducted to investigate the the phenotype and lifespan of roots under cadmium stress (Cd) and melatonin treatment (Cd + MT). The results showed that MT alleviated the decreases in plant height, leaf area, SPAD value, stem diameter, stomatal conductance and net photosynthetic rate under Cd stress, which further promoted the biomass accumulation in various cotton organs. What is more, the Cd + MT treatment increased root volume, surface area, and length under Cd stress by 25.63 %, 10.58 %, and 21.89 %, respectively, compared with Cd treatment. Interestingly, compared to Cd treatment, Cd + MT treatment also significantly extended the lifespan of roots and root hairs by 6.68 days and 2.18 days, respectively. In addition, Cd + MT treatment reduced the transport of Cd from roots to shoots, particularly to bolls, and decreased the Cd bioconcentration factor in bolls by 61.17 %, compared to Cd treatment. In conclusion, these findings show that applying MT externally helps reduce Cd stress by delaying root senescence, promoting root development and regulating Cd transport. This method can be an effective approach to managing Cd stress in cotton.

Prognostic role of the stromal cell derived factor-1 in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: Stromal cell derived factor-1 (SDF-1) plays a pivotal role in the recruitment of stem cells to injured livers. However, the changes of SDF-l in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) have yet to be elucidated. AIM: To study the SDF-1 changes in patients with HBV-related ACLF. METHODS: 30 patients with HBV-related ACLF, 27 patients with chronic hepatitis B and 20 healthy individuals are involved in our study. The SDF-l mRNA expression in liver tissue was detected by quantitative real-time polymerase chain reaction. Immunohistochemical staining was performed to illustrate the expression of SDF-l, CXC receptor 4 (CXCR4) and Ki67. The serum SDF-l concentrations were also detected by enzyme-linked immunosorbent assays. RESULTS: The expression of SDF-1 mRNA from ACLF patients was remarkably higher than that from other patients (both P < 0.05). The expression of SDF-l, CXCR4 and Ki67 from ACLF were the highest among the three groups (all P < 0.01). The serum SDF-l levels in ACLF patients were significantly lower than that in other patients (both P < 0.01). Moreover, in ACLF patients, the serum SDF-1 Levels were positively correlated with serum total bilirubin and international normalized ratio. In addition, the serum SDF-l levels in survival were significantly lower compared with the non-survivals (P < 0.05). The area under the curve for the serum SDF-1 level in predicting 28-d mortality was 0.722 (P < 0.05). CONCLUSION: This study provides the SDF-1 changes in patients with HBV-related ACLF. The SDF-1 Level at admission may serve as a promising prognostic marker for predicting short-term prognosis.

Effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries.

BACKGROUND: The rotator cuff is located below the acromion and deltoid muscles and comprises multiple tendons that wrap around the humeral head, maintaining shoulder joint stability. AIM: To explore the effect of electroacupuncture combined with rehabilitation techniques on shoulder function in patients with rotator cuff injuries. METHODS: We selected 97 patients with rotator cuff injuries treated in the People's Hospital of Yuhuan from February 2020 to May 2023. Patients were grouped using the envelope method. RESULTS: After treatment, the study group's treatment effective rate was 94.90% (46/49 patients), significantly higher than that in the control group (79.17%, 38/48 cases; P < 0.05). Before treatment, there was no difference in Constant Murley Score (CMS) scores, shoulder mobility, or 36-Item Short Form Health Survey (SF-36) scale scores (P > 0.05). Compared with those before treatment, the CMS scores (including pain, daily living ability, shoulder mobility, and muscle strength), all aspects of shoulder mobility (forward flexion, posterior extension, external rotation, internal rotation), and SF-36 scale scores (including physiological, psychological, emotional, physical, vitality, and health status) were higher in both groups after treatment and significantly higher in the study group (P < 0.05). There was no difference in the occurrence of complications between the two treatment groups (P > 0.05). CONCLUSION: Electroacupuncture combined with rehabilitation techniques has a good treatment effect on patients with rotator cuff injuries, helps accelerate the recovery of shoulder function, improves the quality of life, and is highly safe.

Heparin is an effective treatment for preventing liver failure after hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most important causes of death following liver resection. Heparin, an established anticoagulant, can protect liver function through a number of mechanisms, and thus, prevent liver failure. AIM: To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy. METHODS: The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC-III) v1. 4 pinpointed patients who had undergone hepatectomy for liver cancer, subdividing them into two cohorts: Those who were injected with heparin and those who were not. The statistical evaluations used were unpaired t-tests, Mann-Whitney U tests, chi-square tests, and Fisher's exact tests to assess the effect of heparin administration on PHLF, duration of intensive care unit (ICU) stay, need for mechanical ventilation, use of continuous renal replacement therapy (CRRT), incidence of hypoxemia, development of acute kidney injury, and ICU mortality. Logistic regression was utilized to analyze the factors related to PHLF, with propensity score matching (PSM) aiming to balance the preoperative disparities between the two groups. RESULTS: In this study, 1388 patients who underwent liver cancer hepatectomy were analyzed. PSM yielded 213 matched pairs from the heparin-treated and control groups. Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples. Further analysis in the matched cohorts confirmed a significant association, with heparin reducing the risk of PHLF (odds ratio: 0.518; 95% confidence interval: 0.295-0.910; P = 0.022). Additionally, heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations, diminished requirements for respiratory support and CRRT, and lower incidences of hypoxemia and ICU mortality. CONCLUSION: Liver failure is an important hazard following hepatic surgery. During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure. This indicates that heparin may provide a hopeful option for controlling PHLF.

Deletion of GPR81 activates CREB/Smad7 pathway and alleviates liver fibrosis in mice.

BACKGROUND: Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis. METHODS: The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-ß1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-ß1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation. RESULTS: CCl4 exposure or TGF-ß1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-ß1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-ß1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs. CONCLUSION: GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.

FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα-CPT1a pathway.

OBJECTIVES: Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator, FTY720, in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation. METHODS: The effects of FTY720 in EAV were evaluated by quantifying haematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary haemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analysed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis). RESULTS: FTY720 treatment significantly attenuated renal injury and pulmonary haemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferator-activated receptor (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1a (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis. CONCLUSION: FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα-CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment.

Effects of polystyrene microspheres on the swimming behavior and metabolism of grass carp (Ctenopharyngodon idella).

Microplastics (MPs) are a heterogeneous class of pollutants fouling aquatic environments and they are hazardous to aquatic organisms. This study investigated the size-dependent effects of polystyrene microspheres (PSMPs) on the swimming ability, metabolism, and oxidative stress of juvenile grass carp (Ctenopharyngodon idella). Test fish were exposed to four sizes of PSMPs (0.07, 0.5, 5, and 20-µm), and swimming ability was tested after different exposure times (2, 7, and 15 days). To measure the effect on swimming ability, critical swimming speed (Ucrit) was determined, and to assess metabolic effects, oxygen consumption (MO2), routine metabolic rate (RMR), maximum oxygen consumption (MMR), and excess post-exercise oxygen consumption (EPOC) were determined. To assess the effects on oxidative stress, the activities of two antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were determined in the liver and gills of test fish. After exposure to 20 µm PSMPs, there was a significant drop in Ucrit compared to the control group (P<0.05), with decreases of 22 % on Day 2 and Day 7, and 21 % on Day 15. The RMR and MMR increased significantly (P<0.05), the RMR by 23.9 % on Day 2 and the MMR by 17.2 % on Day 2 and on Day 15, 44.7 % and 20.0 % respectively. The EPOC decreased with exposure time, by 31 % (0.07-µm), 45 %-(0.5-µm), 49 % (5-µm), and 57 % (20-µm) after 15 days. Exposure to the larger PSMPs increased CAT and SOD activity more than the smaller PSMPs and the increases began with SOD activity in the gills. The larger PSMPs were consistently more harmful to juvenile grass carp than the smaller PSMPs. Our results clearly show that PSMPs have detrimental effects on juvenile grass carp and provide additional scientific evidence that environmental monitoring and regulation of microplastic pollution is necessary.