Human umbilical cord mesenchymal stem cell （hUC-MSC） as a cell-based therapeutic strategy have demonstrated significant application potential in the field of intervention for neurodegenerative disease （NDD） due to their advantages such as self-renewal， multi-directional differentiation， and low immunogenicity. hUC-MSC effectively intervenes in the pathological features and neurological functions of various disease models such as Alzheimer disease， Parkinson’s disease， amyotrophic lateral sclerosis， and multiple sclerosis primarily through multiple mechanisms such as homing and differentiation， mediating paracrine actions and releasing exosomes， as well as immune regulation and anti-inflammation. Some clinical studies have also preliminarily verified their safety and effectiveness. Currently， its research still faces challenges such as immune rejection reactions requiring further observation， long-term safety needing evaluation， mechanisms of action not being fully elucidated， and slow progress in clinical trials. Future research needs to establish pharmaceutical standards for hUC-MSC， deepen their pharmacological mechanisms and clinical trials， ultimately providing new and effective drug treatment options for patients with NDD.

Background: The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis. Methods: A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms. Results: CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis. Conclusions CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

The development of atherosclerosis （AS） is closely associated with endothelial dysfunction and mitochondrial metabolic abnormalities. These alterations are fundamentally characterized by metabolic reprogramming， in which the tricarboxylic acid （TCA） cycle serves as a central regulatory hub. Disruption of the homeostasis of TCA cycle intermediates， including succinate， α -ketoglutarate， and itaconate， contributes to AS progression through multiple mechanisms， such as the modulation of oxidative stress， inflammation， and glucose and lipid metabolic networks. Owing to their multi-target and multi-pathway regulatory properties， bioactive compounds derived from traditional Chinese medicine （TCM） have demonstrated unique advantages in correcting metabolic dysregulation. Flavonoids， glycosides， and other bioactive constituents of TCM can target key enzymes and metabolites involved in the TCA cycle， thereby restoring aberrant metabolic reprogramming， alleviating endothelial injury induced by oxidative stress， inflammation， and glucose and lipid metabolic disorders， ultimately improving metabolic homeostasis and attenuating the progression of AS.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Objective To investigate the effects of implant length,diameter,and abutment angle on bone stress distributions around maxillary central incisors,and determine the optimal parameter combination.Methods A three-dimensional(3D)model of the maxilla was reconstructed based on CBCT data.Using an orthogonal table,a total of 16 dental implant 3D models were established,varying in length,diameter,and abutment angle.These models were assembled with the maxillary and rigid-body models.Finite element analysis was performed using the transient dynamics module of ANSYS.Orthogonal experiments and one-way analysis of variance(ANOVA)were conducted on the obtained stress data.Results The implant diameter showed a statistically significant effect on the maximum von Mises stress in cortical bone(P=0.010),while implant length(P=0.229)and abutment angle(P=0.844)did not demonstrate a statistical significance.The optimal parameter combination for cortical bone stress was 5.0 mm implant diameter,12 mm implant length,and 0° abutment angle.In cancellous bone,implant length(P=0.001),diameter(P=0.011),and abutment angle(P=0.013)all had statistically significant effects on the maximum von Mises stress.The optimal parameter combination for cancellous bone stress was 14 mm implant length,5.0 mm implant diameter,and 5° abutment angle.Conclusions Implant diameter significantly affects the stress of both cortical and cancellous bone.Clinically,a larger diameter should be preferred to reduce the stress peak.Implant length is the next most important factor,while abutment angle has the least effect.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To construct three photosensitive fusion proteins between protein G C3 domain and Avitag for site-spe-cific biotinylation of goat IgG.Methods:DNA sequences of protein G C3 domain with amber codon mutation and C-terminal containing 1,2,3 Avitag were obtained by chemical synthesis,respectively,and sub-cloned into pTXB1 plasmid to construct three fusion pro-tein expression vectors.Three plasmids and pEVOL-pBpF plasmid were co-transformed into competent bacterium E.coli BL21,respec-tively.Target fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were prepared using genetic codon extension technology,and were purified by His Trap Chelating HP column,then biotinylated by Avitag/BirA system.Photo-conjugation efficiency,crosslink site and antigen-binding activity of photo-conjugates were investigated by SDS-PAGE,control experiment,and competitive ELISA.Results:Three expression vectors were successfully constructed,and three designed photoactivatable fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were successfully expressed with molecular weights consistent with their theoretical values.Heavy-chain conjugation efficiencies of biotinylated fusion protein with goat IgG were 85%with Fc-specific conjugation,and conjugates maintained its antigen-binding activity after photo-conjugation.Conclusion:CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 fusion proteins are successfully prepared,and mediates by those photosensitive fusion proteins,biotins molecules are conjugated to Fc fragment of goat IgG,results site-specific biotinylation of goat IgG.

Objective:To construct three photosensitive fusion proteins between protein G C3 domain and Avitag for site-spe-cific biotinylation of goat IgG.Methods:DNA sequences of protein G C3 domain with amber codon mutation and C-terminal containing 1,2,3 Avitag were obtained by chemical synthesis,respectively,and sub-cloned into pTXB1 plasmid to construct three fusion pro-tein expression vectors.Three plasmids and pEVOL-pBpF plasmid were co-transformed into competent bacterium E.coli BL21,respec-tively.Target fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were prepared using genetic codon extension technology,and were purified by His Trap Chelating HP column,then biotinylated by Avitag/BirA system.Photo-conjugation efficiency,crosslink site and antigen-binding activity of photo-conjugates were investigated by SDS-PAGE,control experiment,and competitive ELISA.Results:Three expression vectors were successfully constructed,and three designed photoactivatable fusion proteins CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 were successfully expressed with molecular weights consistent with their theoretical values.Heavy-chain conjugation efficiencies of biotinylated fusion protein with goat IgG were 85%with Fc-specific conjugation,and conjugates maintained its antigen-binding activity after photo-conjugation.Conclusion:CBpa-Avitag,CBpa-(Avitag)2 and CBpa-(Avitag)3 fusion proteins are successfully prepared,and mediates by those photosensitive fusion proteins,biotins molecules are conjugated to Fc fragment of goat IgG,results site-specific biotinylation of goat IgG.