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.

Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.

Cognitive impairment(CI)is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory,thinking,and judgment.Its etiology and pathogenesis are complex,and there is currently a lack of specific drug interventions.Metformin,as a first-line hypoglycemic drug for type 2 diabetes,not only lowers blood glucose levels but also improves CI.This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer's disease,diabetes cognitive impairment,cognitive impairment after chemotherapy,in order to provide novel insights and approaches for the treatment of CI-related diseases.Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism,reducing insulin resistance,inhibiting neuroinflammation,improving synaptic plasticity,improving mitochondrial dysfunction,regulating gut microbiota and lipid metabolism,etc.Future research needs to be conducted through interdisciplinary collaboration,fully integrating multiple omics data,and combining advanced technologies to further reveal their mechanisms of effect.

Objective:To explore the rehabilitation effects of individual computer story-version magnanimous therapy (ICSMT) on patients with end-stage renal disease undergoing maintenance hemodialysis (MHD).Methods:A total of 120 patients with end-stage renal disease receiving MHD treatment at the Department of Nephrology Hemodialysis Center of Huadu District People's Hospital of Guangzhou from August 2022 to April 2024 were selected as the study subjects.They were randomly divided into control group ( n=60, receiving routine clinical treatment) and ICSMT group ( n=60, receiving routine clinical treatment combined with ICSMT for psychological intervention) by random number table method.The patients in the two groups were evaluated by the self-rating anxiety scale (SAS), self-rating depression scale (SDS), enterprising and magnanimous questionnaire (EMQ), the short-form-36 health survey (SF-36), and activity of daily living scale (ADL) before intervention and at 4-week post-intervention.Blood pressure, blood urea nitrogen (BUN), hemoglobin (Hb), and serum albumin (ALB) levels were also measured before the intervention and at the 4-week post-intervention.The clinical global impression scale (CGI) was used to evaluate clinical efficacy before the intervention, at the 2-week post-intervention, and at the 4-week post-intervention.Statistics analysis was performed using SPSS 29.0.1.0(171). Independent-samples t-test, paired t-test, Mann-Whitney U test and Wilcoxon signed-rank test were used for statistical analysis. Results:After 4 weeks of intervention, the SAS and SDS in the ICSMT group (49.0 (48.0, 50.0), 50.0 (49.0, 51.0)) were significantly lower than those in the control group (51.0 (50.0, 52.0), 52.0 (51.0, 53.0)) (both P<0.001). The enterprising subscore of the EMQ in the ICSMT group (35.0 (32.0, 37.0)) was significantly higher than that in the control group (31.0 (29.0, 34.0)) ( P<0.001). Furthermore, the differences of enterprising and magnanimous subscores between the two groups before and after intervention in the ICSMT group (2.0 (1.0, 4.0), 1.0 (-1.0, 2.0))were significantly higher than those in the control group (-1.0 (-1.0, 0), -1.0 (-1.2, 0)) (both P<0.05). Systolic and diastolic blood pressure values in the ICSMT group (130 (126, 134) mmHg, 85 (80, 88) mmHg)were significantly lower than those in the control group (145 (138, 152) mmHg, 93 (88, 99) mmHg)(1 mmHg=0.133 kPa) after 4 weeks of intervention(both P<0.05). After 4 weeks of intervention, the level of BUN in the ICSMT group (5.5 (3.7, 8.4) mmol/L) was significantly lower than that in the control group (9.1 (6.8, 11.4) mmol/L), while the level of Hb and ALB in the ICSMT group ((115.0±10.0)g/L, (38.3±3.2)g/L)were significantly higher than those in the control group ((104.0±12.0)g/L, (37.1±2.9)g/L) (all P<0.05). After 4 weeks of intervention, the physical functioning, role-physical, general health, vitality, social functioning, role-emotional, and mental health subscores of SF-36 in ICSMT group were all significantly higher than those in the control group (all P<0.05). After 4 weeks of intervention, the score of ADL in the ICSMT group (15.42±1.58)was significantly lower than that in the control group (16.78±2.06) ( t=-4.08, P<0.05). At the 2-week post-intervention and the 4-week post-intervention, the severity of illness (SI) and global improvement (GI) in the ICSMT group were significantly lower than those in the control group, while the efficacy index (EI) in the ICSMT group was significantly higher than that in the control group (all P<0.05). Conclusion:ICSMT can effectively promote the physical, psychological, and social functional rehabilitation of end-stage renal disease patients undergoing MHD, significantly improving their quality of life.

Objective To observe the value of changes of neutrophil-to-lymphocyte ratio(NLR)before and after the first interventional treatment of hepatocellular carcinoma(HCC)for predicting patient's overall survival(OS).Methods Totally 92 HCC patients who underwent the first time TACE or TACE+hepatic artery infusion chemotherapy(HAIC)were retrospectively enrolled.The patients were divided into NLR ratio(NLRR)＜1.29 group(n=54)and≥1.29 group(n=38)based on the ratio of NLR after to before treatment,also ΔNLR＜0.87 group(n=60)and≥0.87 group(n=32)based on the difference of NLR after and before treatment.Clinical data were compared between groups,survival analysis was performed,and the value of NLRR and ΔNLR for predicting OS were analyzed.Results No significant difference of clinical data was found between NLRR＜1.29 and≥1.29 groups,nor between ΔNLR＜0.87 and≥0.87 groups(all P＞0.05).The median OS of 92 patients was 30.90 months,which in NLRR＜1.29 group(55.10 months)was longer than that in NLRR≥1.29 group(22.30 months,P=0.005),while in ΔNLR＜0.87 group(55.10 months)was longer than that in ΔNLR≥0.87 group(14.20 months,P=0.003).Cox regression analysis showed that the maximum diameter of tumor≥5 cm,distant metastasis,ascites,NLRR≥1.29 and ΔNLR≥0.87 were all independent risk factors of OS(all P＜0.05).Taken 1.29 and 0.87 as the best cut-off value,respectively,the area under the curve of NLRR and ΔNLR for predicting OS was 0.620 and 0.610,respectively.Conclusion NLRR and ΔNLR were helpful for predicting OS of HCC patient after the first interventional treatment.

BACKGROUND:Duhuo Jisheng Decoction is a classic prescription for the treatment of rheumatoid arthritis,but its specific mechanism is not clear.Extracellular vesicles have the powerful function of inter-cell communication and signal transmission,and may be the signal carrier for the Decoction.OBJECTIVE:To explore the effects of serum extracellular vesicles treated with Duhuo Jisheng Decoction on the proliferation,migration,invasion,and apoptosis of rheumatoid arthritis fibroblast-like synovial cells.METHODS:The rheumatoid arthritis fibroblast-like synovial cell model was established by co-culturing with tumor necrosis factor-α in vitro.The experiment was divided into five groups:normal group,model group,serum treated with Duhuo Jisheng Decoction group,extracellular vesicles treated with Duhuo Jisheng Decoction group,and extracellular vesicles treated with normal saline group.The optimal concentration and time of drug-containing serum and extracellular vesicles were screened by CCK-8 assay.Expression of inflammatory cytokines in the supernatants of cells in each group was detected by ELISA.The migration ability of rheumatoid arthritis fibroblast-like synovial cells was detected by scratch assay.The invasive ability of cells was measured by Transwell Invasion assay.Hoechst staining was adoped to detect cell apoptosis.The expression levels of apoptosis-related genes and proteins were detected by qRT-PCR and western blot assay.RESULTS AND CONCLUSION:(1)The optimal volume fraction of serum treated with Duhuo Jisheng Decoction was 10%and optimal mass concentration of extracellular vesicles treated with Duhuo Jisheng Decoction was 10 ng/mL;the optimal time for the interaction between the two was 24 hours.(2)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could suppress the expression of inflammatory factors of rheumatoid arthritis fibroblast-like synovial cells(P<0.05),scratch healing(P<0.05),migration and invasion(P<0.05).Moreover,the inhibition of extracellular vesicles treated with Duhuo Jisheng Decoction was more significant(P<0.05).(3)Drug-containing serum and extracellular vesicles treated with Duhuo Jisheng Decoction promoted the apoptosis of rheumatoid arthritis fibroblast-like synovial cells.(4)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could increase the expression of proapoptotic factors Caspase-3,Caspase-9,and Bax(P<0.05)and decrease the expression of antiapoptotic factor Bcl-2(P<0.05).Moreover,extracellular vesicles treated with Duhuo Jisheng Decoction had a more significant regulatory effect on apoptosis-related factors.Above findings indicate that extracellular vesicles treated with Duhuo Jisheng Decoction can inhibit the excessive proliferation,migration,and invasion of rheumatoid arthritis fibroblast-like synovial cells and promote their apoptosis.

BACKGROUND:Duhuo Jisheng Decoction is a classic prescription for the treatment of rheumatoid arthritis,but its specific mechanism is not clear.Extracellular vesicles have the powerful function of inter-cell communication and signal transmission,and may be the signal carrier for the Decoction.OBJECTIVE:To explore the effects of serum extracellular vesicles treated with Duhuo Jisheng Decoction on the proliferation,migration,invasion,and apoptosis of rheumatoid arthritis fibroblast-like synovial cells.METHODS:The rheumatoid arthritis fibroblast-like synovial cell model was established by co-culturing with tumor necrosis factor-α in vitro.The experiment was divided into five groups:normal group,model group,serum treated with Duhuo Jisheng Decoction group,extracellular vesicles treated with Duhuo Jisheng Decoction group,and extracellular vesicles treated with normal saline group.The optimal concentration and time of drug-containing serum and extracellular vesicles were screened by CCK-8 assay.Expression of inflammatory cytokines in the supernatants of cells in each group was detected by ELISA.The migration ability of rheumatoid arthritis fibroblast-like synovial cells was detected by scratch assay.The invasive ability of cells was measured by Transwell Invasion assay.Hoechst staining was adoped to detect cell apoptosis.The expression levels of apoptosis-related genes and proteins were detected by qRT-PCR and western blot assay.RESULTS AND CONCLUSION:(1)The optimal volume fraction of serum treated with Duhuo Jisheng Decoction was 10%and optimal mass concentration of extracellular vesicles treated with Duhuo Jisheng Decoction was 10 ng/mL;the optimal time for the interaction between the two was 24 hours.(2)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could suppress the expression of inflammatory factors of rheumatoid arthritis fibroblast-like synovial cells(P<0.05),scratch healing(P<0.05),migration and invasion(P<0.05).Moreover,the inhibition of extracellular vesicles treated with Duhuo Jisheng Decoction was more significant(P<0.05).(3)Drug-containing serum and extracellular vesicles treated with Duhuo Jisheng Decoction promoted the apoptosis of rheumatoid arthritis fibroblast-like synovial cells.(4)Compared with the model group,serum treated with Duhuo Jisheng Decoction,extracellular vesicles treated with Duhuo Jisheng Decoction,and extracellular vesicles treated with normal saline could increase the expression of proapoptotic factors Caspase-3,Caspase-9,and Bax(P<0.05)and decrease the expression of antiapoptotic factor Bcl-2(P<0.05).Moreover,extracellular vesicles treated with Duhuo Jisheng Decoction had a more significant regulatory effect on apoptosis-related factors.Above findings indicate that extracellular vesicles treated with Duhuo Jisheng Decoction can inhibit the excessive proliferation,migration,and invasion of rheumatoid arthritis fibroblast-like synovial cells and promote their apoptosis.

OBJECTIVE To promote the application of drones in emergency rescue and related fields， expand “low-altitude+ medical” rescue services， and advance the standardization of “low-altitude+medical” distribution services. METHODS The Consensus on Low-altitude Transport and Delivery Services for Emergency Medicines via Drones （2025 Edition） （hereinafter referred to as the Consensus） was jointly initiated by the Division of Therapeutic Drug Monitoring， Chinese Pharmacological Society and the Expert Committee on Precision Medication of the Guangdong Pharmaceutical Association. Guangzhou Red Cross Hospital served as the leading unit， organizing 53 multidisciplinary experts nationwide to participate in drafting and reviewing. A nominal group technique was employed to discuss and finalize the consensus outline， resulting in a preliminary draft. Delphi method was employed， and 11 external review experts were invited to conduct the evaluation. After the experts’ opinions were analyzed and integrated， the Consensus was finalized. RESULTS & CONCLUSIONS The finalized Consensus includes its purpose， principles， and applicable scenarios， basic requirements， and operational procedures for low-altitude transport and delivery of emergency medications； distribution requirements and precautions for controlled substances， fragile medications， and temperature-sensitive medications； and recommendations for emergency medications supplies suitable for the low-altitude transportation and distribution. The release of this Consensus is expected to provide guidance and support for the standardization of “low-altitude+medical” distribution services and the application of low-altitude economy in the healthcare sector.

[Objective]To investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/6J mice were randomly divided into saline group(Saline)and hypertension group(Ang Ⅱ,which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps),and supplemented daily with nicotinamide mononucleotide(300 mg/kg),a precursor of NAD+.Blood pressure,endothelial relaxation function and pulse wave velocity were measured after 4 weeks.Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro.mtROS levels were detected by immunofluorescence staining.RT-PCR was used to detect the mRNA expression of mtDNA,SIRT3 and isocitrate dehydrogenase 2(IDH2).8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of p-eNOS,eNOS,SIRT3 and IDH2 were detected by Western blot.[Results]NMN supplementation reduced blood pressure(P<0.001)and improved endothelial function and arterial stiffness(P<0.001)in hypertensive mice.In vitro,NMN improved endothelial function in Ang Ⅱ-stimulated endothelial cells(P<0.05)and attenuated mitochondrial oxidative stress levels(P<0.001).Mechanistically,NMN elevated SIRT3 activity(P<0.001),which subsequently enhanced IDH activity(P<0.001)and reduced oxidative stress levels in endothelial cells.Conversely,knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function(P<0.001).[Conclusion]NAD+lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.