Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

OBJECTIVE: To compare the clinical efficacy of oblique lateral interbody fusion(OLIF) combined with lateral fixation and transforaminal lumbar interbody fusion(TLIF) in patients with lumbar spinal stenosis. METHODS: Totally 47 patients with lumbar stenosis from November 2018 to December 2021 were analyzed retrospectively and were divided into two groups according to the surgical methods. Among them, 21 cases underwent oblique lumbar interbody fusion supplemental anterolateral screw and rod instrumentation, including 5 males and 16 females, with a mean age of (68.19±6.13) years old ranging 55 to 74 years; the other 26 cases underwent posterior pedicle screw fixation and reduction were recorded, including 8 males and 18 females with a mean age of (65.35±7.64) years old ranging 54 to 78 years. Visual analogue scale(VAS) of pain was recorded to evaluate the degree of low back pain and lower extremity pain. The radiographic parameters were collected to evaluate the efficacy of two approaches including disc height, foraminal height, canal sagittal diameter and cross-sectional area. RESULTS: All operations were completed successfully. The wound healed normally and bone fusion was obtained in the last final follow up. No serious complication was occurred in both groups. One case of dural tear occurred in direct compression group. Four cases of left thigh weakness and pain were recorded in indirect decompression group. The average postoperative follow-up was(21.69±4.37)months in direct compression group, while(20.43±4.80)months in another group. There were no significant difference in bone density, body mass index(BMI), hospital stay, Cobb angel(P>0.05). The differences in intra-operative blood loss, operation time, disc height, foraminal height between two groups were statistically significant(P<0.05). The area and sagittal diameter of the spinal canal in the two groups were significantly improved after surgery(P<0.05). CONCLUSION Both two fusion methods have achieved good clinical results in the treatment of lumbar spinal stenosis, with the advantages of good stability, fast recovery and high fusion rate. Compared with TLIF, the advantage of OLIF has greater advantages in less bleeding and less trauma.
Humans ; Male ; Female ; Spinal Stenosis/surgery* ; Spinal Fusion/methods* ; Aged ; Middle Aged ; Lumbar Vertebrae/surgery* ; Retrospective Studies ; Treatment Outcome

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

As a cheap and effective antibiotic,sulfonamides are often used in animal husbandry.However,their residues in animal-derived foodstuffs will threaten human health.Consequently,a high-performance liquid chromatography(HPLC)method integrated with supramolecular solvent microextraction was successfully established for simultaneous quantification of sulfonamide residues sulfachlorpyridazine,sulfamethoxazole,sulfamethoxypyridazine and sulfadimethoxine in milk matrices.This approach exhibited prominent characteristics of operational simplicity,environmental sustainability,and high extraction efficiency.The supramolecular solvents prepared by tributyl octylphosphine tetrafluoroborate and tetrahydrofuran were employed as extraction solvents.The analytes underwent isolation and concentration via dispersive liquid-liquid microextraction(DLLME)prior to quantitative determination using high-performance liquid chromatography(HPLC).The composition and microscopic morphology of the supramolecular solvent were characterized through a series of analytical techniques,including phase diagram,Fourier transform infrared spectroscopy,scanning electron microscopy,and inverted fluorescence microscopy and so on.The density and pH value of supramolecular solvents were determined.The extraction conditions were optimized through the one-factor experiments.The experimental results demonstrated that under the optimal extraction conditions,the four kinds of sulfonamide antibiotics exhibited excellent linearity within respective detection range(R2 ≥ 0.9998)and the limits of detection(LOD)were 0.67-1.45 μg/L.Compared with literature methods,this approach offered some advantages such as simplicity of operation and less reagent consumption,and could be used for analysis and detection of sulfonamide antibiotic residues in milk samples.The present method provided technical support for food safety regulation and paved a new way for the application of supramolecular solvents in the field of extraction and separation.

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

The gut microbiota regulates intestinal nutrient absorption, participates in modulating host glucolipid metabolism, and contributes to ameliorating glucolipid metabolism disorder. Dysbiosis of the gut microbiota can compromise the integrity of the intestinal mucosal barrier, induce inflammatory responses, and exacerbate insulin resistance and abnormal lipid metabolism in the host. Dangua Humai Oral Liquid, a hospital-developed formulation for regulating glucolipid metabolism, has been granted a national invention patent and demonstrates significant clinical efficacy. This study aimed to investigate the effects of Dangua Humai Oral Liquid on gut microbiota and the intestinal mucosal barrier in a mouse model with glucolipid metabolism disorder. A glucolipid metabolism disorder model was established by feeding mice a high-glucose and high-fat diet. The mice were divided into a normal group, a model group, and a treatment group, with eight mice in each group. The treatment group received a daily gavage of Dangua Humai Oral Liquid(20 g·kg~(-1)), while the normal group and model group were given an equivalent volume of sterile water. After 15 weeks of intervention, glucolipid metabolism, intestinal mucosal barrier function, and inflammatory responses were evaluated. Metagenomics and untargeted metabolomics were employed to analyze changes in gut microbiota and associated metabolic pathways. Significant differences were observed between the indicators of the normal group and the model group. Compared with the model group, the treatment group exhibited marked improvements in glucolipid metabolism disorder, alleviated pathological damage in the liver and small intestine tissue, elevated expression of recombinant claudin 1(CLDN1), occluding(OCLN), and zonula occludens 1(ZO-1) in the small intestine tissue, and reduced serum levels of inflammatory factors lipopolysaccharides(LPS), lipopolysaccharide-binding protein(LBP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). At the phylum level, the relative abundance of Bacteroidota decreased, while that of Firmicutes increased. Lipid-related metabolic pathways were significantly altered. In conclusion, based on the successful establishment of the mouse model of glucolipid metabolism disorder, this study confirmed that Dangua Humai Oral Liquid effectively modulates gut microbiota and mucosal barrier function, reduces serum inflammatory factor levels, and regulates lipid-related metabolic pathways, thereby ameliorating glucolipid metabolism disorder.
Animals ; Gastrointestinal Microbiome/drug effects* ; Mice ; Intestinal Mucosa/microbiology* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred C57BL ; Humans ; Glycolipids/metabolism* ; Lipid Metabolism/drug effects* ; Administration, Oral ; Disease Models, Animal

Objective:To analyze the associated factors and cumulative effects of cardiometabolic multimorbidity (CMM) among residents in southern Xinjiang.Methods:A stratified random cluster sampling method was used to conduct questionnaire surveys, physical examinations and laboratory tests among the personnel of the 51st Brigade, 3rd Division, Xinjiang, in 2016. The multivariate logistic regression, multivariate linear regression, restricted cubic spline, and network analysis methods were used to study the association of lifestyle (smoking, alcohol consumption and physical activity), socioeconomic (occupation, education and marital status) and clinical factors (waist circumference, body mass index and family history) with CMM.Results:A total of 12 773 study subjects were included. The prevalence of cardiovascular metabolic diseases among residents in southern Xinjiang was 52.49%. Specifically, the prevalence rates of dyslipidemia, hypertension, coronary heart disease, diabetes, and stroke were 31.14%, 29.95%, 6.78%, 6.26%, and 2.47%, respectively, and the prevalence of CMM was 19.06%. Multivariate logistic regression analysis revealed that the associations between clinical and socioeconomic factors and CMM significantly increased with higher scores. Specifically, the OR rose from 1.75 (clinical factors) and 1.07 (socioeconomic factors) on a score of 1 to 4.41 and 1.93 on a score of 3, respectively. The association between lifestyle factors and CMM was only observed at higher scores ( OR=1.26, 95% CI:1.07~1.62). The trend test using the scores of each group as continuous variables in the model showed that the risk of disease increased with the accumulation of clinical, socioeconomic and lifestyle factors (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear relationship between the total number of associated factors and CMM ( Poverall<0.05 and Pnon-linear<0.05). Network analysis identified hypertension (strength=0.42) as the “core node” among the five diseases. When analyzing the three types of influencing factors, hypertension (strength=0.68), dyslipidemia (strength=0.47), coronary heart disease (strength=0.37), and clinical factors (strength=0.53) emerged as “core nodes”. In the network of nine associated factors, abnormal waist circumference and BMI (strength=0.90 and 0.84) were identified as “key factors”, while hypertension (strength=0.68) and dyslipidemia (strength=0.52) were identified as “key diseases”. Conclusion:The prevalence of CMM among residents in southern Xinjiang is high, and there is a cumulative effect of multiple factors. Hypertension and dyslipidemia are key diseases in the multimorbidity network, while abnormal BMI and waist circumference are key associated factors.