Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To compare the cost-effectiveness between sodium valproate and levetiracetam in the treatment of childhood epilepsy and provide an economic basis for clinical medication choices. Methods A cost-effectiveness analysis was conducted using a decision tree model to compare the effectiveness and drug costs of sodium valproate and levetiracetam in treating childhood epilepsy. Single-factor sensitivity analysis and probabilistic sensitivity analysis were used to assess the impact of parameter variations on the study results. Results The treatment cost of levetiracetam was significantly higher than that of sodium valproate. The incremental cost-effectiveness ratio （ICER） of levetiracetam compared to sodium valproate was ¥8 628.43. Sensitivity analysis results were consistent with the base-case analysis. The probabilistic sensitivity analysis showed that, over a 6-month treatment period, levetiracetam became a more cost-effective option when the willingness-to-pay （WTP） threshold was ¥9,000 or higher. One-way sensitivity analysis revealed that the price of levetiracetam was the most influential factor affecting the ICER. Conclusion When the WTP per effective pediatric epilepsy case is ¥9,000 or higher, levetiracetam demonstrates a cost-effectiveness advantage.

Artificial intelligence (AI) has been widely used in all walks of life, including healthcare, and has shown great application value in the auxiliary diagnosis of pulmonary nodules in the medical field. In the face of a large amount of lung imaging data, clinicians use AI tools to identify lesions more quickly and accurately, improving work efficiency, but there are still many problems in this field, such as the high false positive rate of recognition, and the difficulty in identifying special types of nodules. Researchers and clinicians are actively developing and using AI tools to promote their continuous evolution and make them better serve human health. This article reviews the clinical application and research progress of AI-assisted diagnosis of pulmonary nodules.

Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

Aim To investigate the effect of quercetin(Que)on podocyte inflammatory injury and the under-lying mechanism.Methods MPC5 cells were divided into normal glucose group(NG),mannitol group(MA),high glucose group(HG)and high glucose+quercetin group(HG+Que).Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry.The expression of SIRT1,STAT3,apoptosis-related proteins(Bax,Bcl-2,caspase-3)and pyroptosis pro-tein GSDME was detected by Western blot.The ex-pression levels of inflammatory factors(IL-6,TNF-α,IL-18,IL-1β)in cell supernatants were detected by ELISA.Then small interfering RNA technology was used to knockdown SIRT1 expression.To further eval-uate the biological significance of SIRT1 in response to high glucose and Que treatment,negative control group(HG+si-NC+Que)and SIRT1 interference group(HG+si-SIRT1+Que)were added in the presence of high glucose and Que.Results Compared with the high glucose group,40 μmol·L-1 Que could alleviate the apoptosis of MPC5 cells induced by high glucose,decrease the expression of apoptosis related protein Bax and caspase-3,as well as increase the expression of anti-apoptotic protein Bcl-2;ELISA results showed that Que could decrease the expression of TNF-α,IL-6,IL-1 β and IL-18 induced by high glucose.Mechanical-ly,Que could alleviate the inhibitory effect of high glu-cose on the expression of SIRT1,and further decrease the activation of STAT3 and N-GSDME,and inhibit pyroptosis.Compared with the si-NC group,si-SIRT1 group could reverse the protective effect of Que on the high glucose induced inflammatory damage of podo-cytes,the expression of apoptotic proteins Bax and caspase-3 increased,while the expression of anti-apop-totic protein Bcl-2 decreased.At the same time,the levels of inflammatory cytokines TNF-α,IL-6,IL-1 βand IL-18 in supernatants increased,and the expres-sion of STAT3 and N-GSDME increased.Conclusion Que could inhibit pyroptosis and relieve the inflam-matory damage of podocytes through SIRT1/STAT3/GSDME pathway.

Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60～175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2～6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27～88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50～315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.

Coronary chronic total occlusion(CTO)presents one of the most formidable challenges in percutaneous coronary intervention(PCI).Left ventricular systolic dysfunction(LVSD)is frequently observed in patients undergoing CTO-PCI,who often present with more complex coronary artery lesions and a higher burden of comorbidities,leading to an elevated risk of PCI-related complications.The clinical benefits of revascularization for these patients remain controversial.How to optimize the CTO-PCI strategy and postoperative management to improve patient outcomes represents an urgent issue.This review comprehensively summarizes the clinical characteristics,interventional benefits,interventional strategies,postoperative management,as well as the short-and long-term outcomes for patients with LVSD and CTO,aiming to provide a reference for optimizing the outcome of PCI in this unique and challenging patient subgroup.