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.

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.

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.

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 changes in the levels of serum visinin-like protein-1(VILIP-1)and soluble triggering receptor expressed on myeloid cells-1(sTREM-1)in patients with acute cerebral hem-orrhage(ACH)and their correlation with the degree of neurological deficits and prognosis.Methods Totally 115 cases of ACH patients admitted to this hospital from January 2021 to January 2023 were selected as the ACH group,and another 115 healthy volunteers with physical examination in the same period were selected as the control group.The ACH patients were divided into mild deficit group(39 cases),moderate deficit group(46 cases)and severe deficit group(30 cases)according to the degree of neurological deficit assessed by the national institutes of health stroke scale(NIHSS).Patients with ACH were divided into a poor prognosis group(27 cases)and a good prognosis group(88 cases)after 90 d of follow-up according to the prognosis as-sessed by the modified Rankin scale.Serum VILIP-1 and sTREM-1 levels were measured by enzyme-linked immunosorbent assay.Spearman correlation was used to analyze the correlation between NIHSS scores and se-rum VILIP-1 and sTREM-1 levels in ACH patients,a multifactorial Logistic regression model was set up to analyze the factors affecting the prognosis of ACH patients,and the predictive value of serum VILIP-1 and sTREM-1 levels in poor prognosis in ACH patients was analyzed by plotting the receiver operating character-istic(ROC)curve.Results Compared with the control group,serum VILIP-1 and sTREM-1 levels were ele-vated in the ACH group(P＜0.05).Serum VILIP-1 and sTREM-1 levels increased sequentially in the mild-deficiency,moderate-deficiency,and severe-deficiency groups(P＜0.05).Spearman correlation analysis showed a positive correlation between NIHSS scores and serum VILIP-1 and sTREM-1 levels in ACH patients(r=0.792 and 0.781,both P＜0.001).After 90 d of follow-up,the incidence of poor prognosis in 115 ACH patients was 23.48％(27/115).Multifactorial Logistic regression analysis showed that increased hematoma volume and elevated NIHSS score,VILIP-1,and sTREM-1 were independent risk factors affecting the progno-sis of patients with ACH(P＜0.05).ROC curve analysis showed that the area under the curve of serum VIL-IP-1 and sTREM-1 levels combined to predict poor prognosis in ACH patients was 0.872,which was greater than that of serum VILIP-1 and sTREM-1 levels alone,which were 0.784 and 0.772(P＜0.05).Conclusion Ele-vated serum VILIP-1 and sTREM-1 levels in ACH patients are closely associated with increased degree of neurological deficit and poor prognosis,and the combined detection of serum VILIP-1 and sTREM-1 has high predictive value for poor prognosis in ACH patients.

Objective We aimed to investigate the relationship between microscopic pattern of blood stasis and renal pathological grade and related physical and chemical indexes in children with Henoch-Sch?nlein purpura nephritis(HSPN).Methods We conducted a retrospective analysis of 800 HSPN children from the medical records of the First Affiliated Hospital of Henan University of Chinese Medicine.Laboratory indicators(blood routine test,urine routine test,coagulation test,liver function)and renal pathological indicators of them were collected.According to the severity of renal pathological microscopic lesions,the microscopic pattern of blood stasis was divided into three types,including choroidal discord,dead blood coagulation and intracarenal disease accumulation.The classification of renal microscopic pattern of blood stasis and the correlation between laboratory indexes and renal pathological index were analyzed by Spearman grade correlation and binary Logistic regression analysis.Results(ⅰ)There was no statistical difference of the distribution of the renal microscopic pattern of blood stasis in the different traditional Chinese medicine patterns.(ⅱ)There were significant differences in the contents or the grade of albumin and fibrinogen in the HSPN children with different microscopic pattern of blood stasis(all P＜0.05).(ⅲ)The maximum area under the receiver operating characteristic(ROC)curve between fibrinogen and intracarenal disease accumulation was 0.594(95％CI from 0.540 to 0.633,P＜0.001);sensitivity was 0.447,specificity was 0.725;the best threshold on the ROC curve of 0.172 was 3.755 g/L.(ⅳ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the scores of intracarenal disease accumulation type(r=0.176,r=0.315,r=0.656;all P＜0.001).(ⅴ)There were positive correlations between the content of fibrinogen,ISKDC grade and Bohle A grade respectively with the renal microscopic pattern of blood stasis(r=0.157,r=0.377,r=0.429;all P＜0.001).Conclusion The microscopic renal pattern of blood stasis can not only reflect the severity of renal blood stasis,but also reflect the severity and long-term prognosis of renal diseases.Albumin and urinary protein grade can reflect the early stage of the microscopic renal pattern of the blood stasis(choroidal discord).The content of fibrinogen increases with the aggravation of renal microscopic pattern of blood stasis,reflecting the end-stage of HSPN,which has the correlation with the formation and severity of related indexes.Fibrinogen can be used as a laboratory indicator to assist in the diagnosis of irreversible lesionsin the renal pathology of HSPN children.

Objective We investigated the effects of Xueguan Ruanhua Pills(XGRHW) on ferroptosis in ApoE-/- atherosclerotic mice through the nuclear factor E2 related factor 2 (Nrf2)/xCT/glutathione peroxidase 4 (GPX4) signaling pathway.Methods Ten male C57BL/6J mice in the normal group were fed normal chow. Additionally, 50 ApoE-/- mice were fed high-fat chow for 12 weeks, and were divided into the following five groups (10 mice per group): the model group, the XGRHW low-dose (2.34g/kg) group, the XGRHW high-dose (4.68 g/kg) group, the XGRHW high-dose combined with the Nrf2 inhibitor ML385 (0.03 g/kg) group, and the ferrostatin-1 (1 mg/kg) group. Drugs were administered for 6 weeks. The blood levels of four types of lipids were detected by an automatic lipid analyzer, lipid deposition in the aorta was observed by Oil Red O staining, histomorphological changes in the aortic sinus were observed by HE staining, the serum levels of Fe2+, MDA, GSH, and SOD were determined by colorimetric assays, and the expression levels of FTH1 and FTL in the aortic sinus were observed by immunofluorescence. The protein levels of Nrf2, xCT, and GPX4 in mouse aortic tissues were detected by Western blotting. The ultrastructural changes of aortic mitochondria were observed by transmission electron microscopy.Results Compared with the normal group, mice in the model group showed obvious lipid plaque deposition in the aorta, severely calcified lesions in the aortic sinus, elevated serum levels of TC, TG, LDL-C, Fe2+, and MDA, decreased levels of HDL-C, SOD, and GSH (P<0.01), and decreased protein expressions of aortic Nrf2, xCT, and GPX4 as well as the iron storage proteins FTH1 and FTL (P<0.01), and serve damage to mitochondrial structure and morphology. Compared with the model group, the relative aortic plaque area was decreased, calcified lesions in the aortic sinus were decreased, serum levels of TC, TG, LDL-C, Fe2+, and MDA were decreased, and HDL-C, SOD, and GSH levels were increased in the XGRHW low-dose and high-dose and ferrostatin-1 groups (P<0.05 or P<0.01), and Nrf2, xCT, GPX4, and the iron storage proteins FTH1 and FTL were upregulated in aortic tissues (P<0.05 or P<0.01), and mitochondrial structure approaching normal. In the XGRHW high-dose+ML385 group, compared with the XGRHW high-dose group, the levels of blood lipids and lipid peroxidation were increased and the protein levels of Nrf2, xCT, and GPX4 in aortic tissue and the iron storage proteins FTH1 and FTL were decreased (P<0.01), and mitochondrial structure was damaged indicating that ML385 could inhibit the therapeutic effect of the XGRHW in atherosclerotic mice.Conclusion The XGRHW can improve blood lipid levels and reduce the degree of arterial plaque lesions in atherosclerotic mice, and its mechanism of action may be related to activation of the Nrf2/xCT/GPX4 pathway to inhibit ferroptosis.

Objective To analyze the predictive value of serum micro RNA(miR)-411-5p and micro RNA(miR)-485-5p levels in preeclampsia(PE)pregnant women combined with ultrasound blood flow indicators for perinatal outcomes.Methods A total of 88 pregnant women with PE who were enrolled in the obstetric card and underwent cesarean section in Beijing Nuclear Industry Hospital from January 2020 to December 2021 were selected as the study subjects(PE group).In addition,90 normal pregnant women who delivered by cesarean section due to other reasons in the same period were regarded as the control group.The differences of pulsitility index(PI)and resistance index(RI)were compared between the two groups.The serum levels of miR-411-5p and miR-485-5p were measured and compared between the two groups by real time fluorescent quantitative PCR(qRT-PCR).According to the different perinatal outcomes of PE patients,they were grouped into good outcome group and poor outcome group.The differences of PI,RI,miR-411-5p and miR-485-5p between the two groups were compared.The predictive effect of PI,RI,miR-411-5p,miR-485-5p and combined detection on the adverse perinatal outcome of PE patients was analyzed by the receiver operating characteristic(ROC)curve method.Results The RI(0.79±0.08)and PI values(1.82±0.08)of pregnant women in the PE group were higher than those in the control group(0.66±0.06,1.38±0.15),the serum levels of miR-411-5p(0.32±0.09)and miR-485-5p(0.26±0.03)were lower than those in the control group(1.01±0.08,1.02±0.09),and the differences were statistically significant(t=12.283,24.339,54.091,75.231,all P＜0.001).The RI(0.83±0.08)and PI(1.86±0.09)values of PE patients in the poor outcome group were higher than those in the good outcome group(0.70±0.07,1.71±0.07),the serum levels of miR-411-5p(0.27±0.02)and miR-485-5p(0.24±0.02)were lower than those in the good outcome group(0.45±0.04,0.31±0.04),and the differences were statistically significant(t=11.545,12.428,37.840,14.716,all P＜0.001).The areas under the curve of ultrasound blood flow index RI and PI to predict the adverse perinatal outcome of PE patients were 0.838(sensitivity was 90.8％,specificity was 65.2％),and 0.758(sensitivity was 50.8％,specificity was 91.3％),respectively.The areas under the curve of serum miR-411-5p and miR-485-5p in predicting adverse perinatal outcome of PE patients were 0.830(sensitivity was 90.8％,specificity was 73.9％),and 0.769(sensitivity was 95.4％,specificity was 61.9％),respectively.The area under the curve of the four combined tests to predict the adverse perinatal outcome of PE patients was 0.976(sensitivity was 98.5％,specificity was 91.3％).Conclusion The levels of miR-411-5p and miR-485-5p in serum of PE pregnant women were decreased,and the combination of miR-411-5p and miR-485-5p and ultrasound blood flow indicators PI and RI may predict the perinatal fetal outcome of PE pregnant women.

Objective To explore the expression levels of serum glycerophospholipid metabolites lysophosphatidylcholine(LPC)18∶3 and lysophosphatidylethanolamine(LPE)16∶1 in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and their correlation with clinical prognosis.Methods A total of 112 AECOPD patients diagnosed and treated in Tangshan People's Hospital from January 2019 to January 2022 were selected as the AECOPD group.According to the 3-month follow-up prognosis of the AECOPD group patients,they were divided into survival group(n=90)and death group(n=22).During the same period,60 stable COPD patients were selected as the stable period group,while 60 healthy individuals in the same period were selected as the control group.High performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)was used to detect serum LPC18∶3 and LPE16∶1 levels in each group.Pearson method was used to analyze their correlation.Logistic regression analysis was used to analyze factors affecting the prognosis of AECOPD patients.Receiver operating characteristic curve was drawn to evaluate the prognostic value of LPC18∶3 and LPE16∶1 in AECOPD patients.The prognosis of AECOPD patients with different serum LPC18∶3 and LPE16∶1 expression groups was compared by K-M curve.Results Serum LPC18∶3(21.67±4.35 μ mol/L),LPE16∶1(16.20±5.17 μ mol/L),PEF％pred,FEV1％pred,and FEV1/FVC％in AECOPD group were lower than those of stable phase group(43.24±6.17 μ mol/L,32.19±5.98 μmol/L)and the control group(68.14±8.78 μ mol/L,44.82±7.44 μ mol/L),with significant differences(F=461.240～1 102.534,all P＜0.05).The serum LPC18:3 and LPE16:1 levels in the AECOPD group were positively correlated with lung function indicators such as PEF％pred,FEV1％pred,and FEV1/FVC％(r=0.603～0.756,allP＜0.05).The course of COPD and PCT of AECOPD patients in the death group were higher than those in the survival group(t=3.961,2.509),while the PEF％pred,FEV1％pred,FEV1/FVC％,serum LPC18∶3(17.20±4.11μ mol/L),and LPE16∶1(10.15±3.03 μ mol/L)in the death group were lower than those in the survival group(22.76±4.35 μ mol/L,17.68±5.22 μ mol/L),with significant differences(t=4.141～6.490,all P＜0.05).Serum LPC18∶3(OR=0.691,95％CI:0.519～0.920)and LPE16∶1(OR=0.586,95％CI:0.382～0.901)were independent protective factors,while the course of COPD(OR=1.510,95％CI:1.203～1.895)and procalcitonin(OR=1.759,95％CI:1.159～2.671)were risk factors affecting the prognosis of AECOPD patients.The area under the curve(95％CI)of combined serum LPC18∶3 and LPE16∶1 for prognosis evaluation of AECOPD patients was better than that of serum LPC18∶3 and LPE16∶1 predicted separately[0.866(0.822～0.907)vs 0.794(0.748～0.830),0.786(0.739～0.836)](Z=3.957,4.195,P=0.002,＜0.001).The mortality risk of AECOPD patients in the low expression group of LPC18∶3 and LPE16∶1 was higher than that in the high expression group of LPC18∶3 and LPE16∶1(log rankx2=4.475,5.763,P=0.034,0.016).Conclusion The serum levels of glycerophospholipid metabolites LPC18∶3 and LPE16∶1 in AECOPD patients were decreased,which were related to lung function status.The combination of the two may effectively evaluate the prognosis of AECOPD patients.