OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Polycythemia vera (PV) is a BCR-ABL1-negative myeloproliferative neoplasm characterized by the proliferation of all three hematopoietic cell lines to varying degrees. It is commonly associated with mutations such as JAK2 V617F or mutations in exon 12 of the JAK2 gene. These genetic alterations contribute to a range of clinical manifestations, including thrombosis, bleeding tendencies, splenomegaly, and disturbances in microcirculation. Phlebotomy serves as a first-line therapeutic approach for PV by reducing hematocrit levels to a target below 45%, which effectively decreases blood viscosity and thereby lowers the risk of thrombosis. As such, phlebotomy plays a crucial role in the management of PV. This review systematically summarizes recent research advances on phlebotomy for PV, aiming to support the development of individualized treatment approaches for patients with PV.

Objective: To reveal the molecular basis of the cisAB (p. Met266Leu) glycosyltransferase by studying a proband with cisAB subtype and his family. Methods: A male newborn was selected as the research subject. Tube methods were used to identify ABO blood types of the proband and his family members. PCR-SSP detection, ABO gene sequencing, and cloning analysis were performed on the proband and some family members. The inheritance pattern of the subtype gene in the family was determined through pedigree analysis. Homology modeling was used to analyze the impact of amino acid variations on the structure of the transferase, and molecular docking was used to demonstrate the bifunctional activity of the transferase and the donor-receptor binding conformation. Results: Serological tests showed that the proband and his father had enhanced anti-H agglutination, and the grandmother had a forward and reverse discrepancy. Sequencing of the proband revealed heterozygous variations of c. 297A>G, c. 526C>G, c. 657C>T, c. 703G>A, c. 803G>C, and c. 930G>A compared with A1. 01 (compared with B. 01, lacking the c. 796C>A variation, namely harboring the c. 796A>C variation) and c. 261delG. Combined with cloning analysis, the proband's genotype was determined to be ABO cisAB (c. 796A>C)/ABO O. 01. 01, the father's genotype was ABO cisAB (c. 796A>C)/ABO O. 01. 02, and the grandmother's genotype was ABO cisAB (c. 796A>C)/ABO B102. Pedigree analysis indicated that the cisAB allele in this newborn was inherited from his father and grandmother rather than a natural mutation. Homology modeling showed that the side chain orientation and intermolecular forces of Leu266 in the cisAB (p. Met266Leu) transferase changed, and molecular docking demonstrated that the "binding pocket" of the active center of the variant enzyme could accommodate both UDP-GalNAc and UDP-Gal, indicating that the cisAB enzyme structure has bifunctional activity. Conclusion: The bifunctional activity of this cisAB (p. Met266Leu) enzyme is related to the nucleotide variation of c. 796A>C, and molecular docking indicates that the enzyme has dual affinity for A/B sugar donors.

Objective:To investigate the epidemiological characteristics of sepsis-associated encephalopathy (SAE) in patients with sepsis, analyze its risk factors and build a prediction model, which provides evidence for early clinical identification of SAE patients and improvement of clinical outcomes.Methods:A retrospective observational study was conducted. Sepsis patients admitted to the critical care medical center of the First Affiliated Hospital of Xinjiang Medical University from February 2022 to February 2023 were enrolled. According to whether SAE occurred, the patients were divided into sepsis group and SAE group. The 24 patients without sepsis in the same period were used as controls (non-sepsis group). Demographic data, relevant scores and laboratory test indicators at admission to intensive care unit (ICU), and prognostic indicators were collected. Univariate and multivariate Logistic regression analysis was used to analyze the risk factors for sepsis and SAE. Receiver operator characteristic curve (ROC curve) was drawn. The predictive value of each risk factor for sepsis and SAE.Results:A total of 130 patients with sepsis were included, of which 52 had SAE, and the incidence of SAE was 40.00%. There were significant differences in the length of ICU stay and total length of stay among all groups, while there were no significant differences in hospitalization cost and mechanical ventilation time. Multivariate Logistic regression analysis showed that pulmonary infection [odds ratio ( OR) = 46.817, 95% confidence interval (95% CI) was 5.624-389.757, P = 0.000], acute physiology and chronic health evaluation Ⅱ (APACHEⅡ: OR = 1.184, 95% CI was 1.032-1.358, P = 0.016), sequential organ failure assessment (SOFA: OR = 9.717, 95% CI was 2.618-36.068, P = 0.001), Charson comorbidity index (CCI: OR = 4.836, 95% CI was 1.860-12.577, P = 0.001), hemoglobin (Hb: OR = 0.893, 95% CI was 0.826-0.966, P = 0.005), glutamyltranspeptidase ( OR = 1.026, 95% CI was 1.008-1.045, P = 0.006) were independent risk factors for sepsis in ICU patients. Pulmonary infection ( OR = 28.795, 95% CI was 3.296-251.553, P = 0.002), APACHEⅡ score ( OR = 1.273, 95% CI was 1.104-1.467, P = 0.001), SOFA score ( OR = 8.670, 95% CI was 2.330-32.261, P = 0.001), CCI ( OR = 5.141, 95% CI was 1.961-13.475, P = 0.001), Hb ( OR = 0.922, 95% CI was 0.857-0.993, P = 0.031), glutamyltranspeptidase ( OR = 1.020, 95% CI was 1.002-1.038, P = 0.030) were independent risk factors for SAE in sepsis patients. ROC curve analysis showed that the area under the curve (AUC) of pulmonary infection, APACHEⅡ score, SOFA score, CCI, Hb, and glutamyltranspeptidase for predicting sepsis were 0.792, 0.728, 0.987, 0.933, 0.720, and 0.699, respectively; the AUC of the combined prediction of the above 6 variables for sepsis was 1.000, with a sensitivity of 100% and a specificity of 100%. The AUC predicted by pulmonary infection, APACHEⅡ score, SOFA score, CCI, and Hb for SAE were 0.776, 0.810, 0.907, 0.917, and 0.758, respectively; the AUC of the combined prediction of the above 5 variables for SAE was 0.975, with a sensitivity of 97.3% and a specificity of 93.1%. Conclusions:Sepsis is more severe when accompanied by encephalopathy. Pulmonary infection, Hb, APACHEⅡ score, SOFA score and CCI were independent risk factors of SAE. The combination of the above five indicators has good predictive value for early screening and prevention of the disease.

Objective:To test the reliability and validity of the general procrastination scale (GPS) in the application of middle school students.Methods:The Chinese version of GPS, the irrational procrastination scale(IPS), and the Maslach burnout inventory(MBI) were utilized to survey 10 825 middle school students in Harbin City through stratified random sampling, and 4 498 students were retested after 4 weeks. Statistical analysis was performed using SPSS 27.0 and Mplus 8.0.Results:The entries were well differentiated.Exploratory and confirmatory factor analysis indicated that GPS was composed of two factors, including active avoidance and lack of planning.The model fit was good (CFI=0.914, TLI=0.901, RMSEA=0.069, SRMR=0.072). GPS was positively correlated with the total scores of IPS and MBI ( r=0.753, 0.677, both P<0.001). The Cronbach's α coefficient of GPS was 0.864, the folded half reliability was 0.870, and the retest reliability after 4 weeks was 0.756. Conclusion:The GPS has good reliability and validity among middle school students, which provides a standard for measuring the procrastination level of middle school students and carrying out related research.

Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

Objective:To analyze the clinical features of postpartum hepatitis flares in pregnant women with hepatitis B virus (HBV) infection.Methods:A retrospective study was conducted. Patients who met the enrollment criteria were included. Liver function and HBV virology tests were collected from pregnant women with chronic HBV infection at delivery, 6, 24, 36, and 48 weeks after delivery through the hospital information and test system. Additionally, antiviral therapy types and drug withdrawal times were collected. Statistical analysis was performed on all the resulting data.Results:A total of 533 pregnant women who met the inclusion criteria were included, with all patients aged (29.5±3.7) years old. A total of 408 cases received antiviral drugs during pregnancy to interrupt mother-to-child transmission. There was no significant difference in the levels of alanine aminotransferase (ALT, z ?=?-1.981, P ?=?0.048), aspartate aminotransferase (AST, z ?=?-3.956, P ?

Objective To investigate the relationship of miRNA gene polymorphisms with blood pressure(BP)responses to the sodium and potassium diet intervention.Methods In 2004,we recruited 514 participants from 124 families in seven villages of Baoji,Shaanxi Province,China.All subjects were given a three-day normal diet,followed by a seven-day low-salt diet,a seven-day high-salt diet,and finally a seven-day high-salt and potassium supplementation.A total of 19 miRNA single nucleotide polymorphisms(SNPs)were selected for analysis.Results Throughout the sodium-potassium dietary intervention,the BP of the subjects fluctuated across all phases,showing a decrease during the low-salt period and an increase during the high-salt period,followed by a reduction in BP subsequent to potassium supplementation during the high-salt diet.MiR-210-3p SNP rs 12364149 was significantly associated with systolic BP(SBP),diastolic BP(DBP)and mean arterial pressure(MAP)responses to low-salt diet.MiR-4638-3p SNP rs6601178 was significantly associated with SBP while miR-26b-3p SNP rs115254818 was significantly associated with MAP responses to low-salt intervention.In addition,miR-26b-3p SNP rs115254818 was significantly correlated with SBP,DBP and MAP responses to high-salt intervention.MiR-1307-5p SNPs rs1 1191676 and rs2292807 were associated with SBP and MAP responses to high-salt diet.MiR-4638-3p SNP rs6601178,miR-210-3p SNP rs12364149,miR-382-5p SNP rs4906032 and rs4143957 were significantly associated with SBP response to high-salt diet.In addition,miR-26b-3p SNP rs115254818 was significantly associated with SBP,DBP and MAP responses to potassium supplementation.MiR-1307-5p SNPs rs11191676,rs2292807,and miR-19a-3p SNP rs4284505 were significantly associated with SBP responses to high-salt and potassium supplementation.Conclusion miRNA gene polymorphisms are associated with BP response to sodium and potassium,suggesting that miRNA genes may be involved in the pathophysiological process of salt sensitivity and potassium sensitivity.