Objective To investigate the in vitro drug release behavior of hydroxyapatite-wedelolactone(Hap-Wed)and its effect on promoting osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods The in vitro release behavior of Hap-Wed fusion materials was detected by chromatographic technique.After the cells were passed continuously up to the third generation,they were divided into:① control group:complete medium;② Os group:osteogenic inducer(1mmol/L dexamethasone,10mmol/L vitamin C,1mol/L β-glycerol phosphate);③ Wed group:1μg/ml Web and osteogenic inducer were added to the complete medium;④ Hap-Web group:1 μg/ml Web,osteogenic inducer and Hap were added to the complete medium.Alkaline phosphates(ALP)activity assay,alizarin red S staining assay,real-time quantitative polymerase chain reaction(RT-qPCR)detection of osteocalcin,Osterix and Runx2 gene expression,analysis of Hap-Wed on BMSCs osteoblast differentiation.Results Hap-Wed fusion material released the drug slowly.Compared with control group,the number of ALP staining and the number of calcified nodules increased significantly in Hap-Wed experimental group.The Hap-Wed experimental group increased gene expression of osteocalcin,Osterix and Runx2.Conclusion Hap-Wed fusion material can slow and effective stimulation of osteoblast differentiation,which may provide a promising application prospect for the future development of the carrier material.

Ischemic stroke is more common in the elderly, characterized by rapid onset, high incidence, high disability rate, and high mortality rate.It often causes severe cellular dysfunction and brain damage, imposing a significant burden on families and society.Death-associated protein kinase 1(DAPK1)is a calcium/calmodulin(Ca 2+ /CaM)-dependent serine/threonine(Ser/Thr)protein kinase that plays a crucial role in regulating brain damage caused by ischemic stroke.Studies have shown that DAPK1 activity is regulated by phosphorylation and mediates the pathophysiological processes of ischemic stroke through multiple signaling pathways, including DAPK1-N-methyl-D-aspartate(DAPK1-NMDA), DAPK1-NMDA), DAPK1-tumor suppressor protein p53(DAPK1-p53), DAPK1-microtubule-associated protein Tau(DAPK1-Tau), and DAPK1-dangerous signaling(DAPK1-DANGER), among others.Blocking these signaling pathways can significantly improve neuronal damage following ischemic stroke.This article reviews the related signaling pathways, mechanisms of action, and progress in targeted drug development of DAPK1 in ischemic stroke, aiming to provide references for future research and treatment of ischemic stroke.

Objective:To investigate the impact of immunosuppressive therapy on the severity of SARS-CoV-2 infection and cytokine levels in pediatric patients with kidney diseases.Methods:A retrospective analysis was conducted on the clinical data of 40 hospitalized pediatric patients who were diagnosed with SARS-CoV-2 infection at the 900th Hospital of PLA Joint Logistic Support Force from December 2022 to February 2023. Based on their immunosuppressive status prior to SARS-CoV-2 infection, these patients were categorized into immunosuppressive group and non-immunosuppressive group. Independent sample t-tests, Mann-Whitney U tests, and χ2 test were employed to compare the clinical baseline characteristics and laboratory data, the severity of SARS-CoV-2 infection, and the levels of cytokines between the 2 groups. Results:Among the 40 patients, 11 were in the immunosuppressive group (aged 13 (8, 14) years, 9 males and 2 females) and 29 in the non-immunosuppressive group (aged 2 (1, 4) years, 15 males and 14 females). In the immunosuppressive group, 2 were asymptomatic cases, 8 were mild cases, and 1 was moderate case, and there was no severe or critical cases. In the non-immunosuppressive group, 8 were mild cases, 5 were moderate, 15 were severe cases, 1 was critical case, and no asymptomatic cases. The underlying diseases in the immunosuppressive group included nephrotic syndrome (6 cases), IgA vasculitis nephritis (2 cases), lupus nephritis (1 case), post-renal transplantation (1 case), and renal failure (1 case), with a mean total immunosuppression score (TIS) of (3.6±1.4) points. In the non-immunosuppressive group, 2 patients had a history of epilepsy, and the remaining 27 cases had no underlying conditions, all with TIS scores of 0. Compared to the children in the non-immunosuppressive group, those in the immunosuppressive group were more likely to exhibit asymptomatic or mild infection, with lower risks of severe disease, cytokine storm, fever, and cough, but a higher risk of fatigue ( OR=1.22, 2.66, 0.48, 0.12, 0.12, 0.13, 1.22; 95% CI 0.93-1.62, 0.99-7.15, 0.33-0.70, 0.03-0.57, 0.03-0.57, 0.03-0.65, 0.93-1.62; all P<0.05). The levels of cytokine IL-6, interferon-α and interferon-γ in the immunosuppressive group were all lower than those in the non-immunosuppressive group ( Z=2.23, 2.51, 2.92, respectively; all P<0.05). Conclusion:Pediatric patients with kidney diseases receiving appropriate immunosuppressive therapy may mitigate the severity of SARS-CoV-2 infection by suppressing the expression of cytokines.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

Objective To quantify the intraretinal fluid(IRF)volume in patients with diabetic macular edema(DME)using a deep learning-based three-dimensional segmentation model and to investigate the relationship of IRF volume with visual function and retinal biomarkers based on optical coherence tomography(OCT).Methods A total of 37 pa-tients(42 eyes)with DME who received treatment in the Ophthalmology Department of Sichuan Provincial People's Hospi-tal from July 2022 to September 2024 were prospectively included in this study.A three-dimensional segmentation model was used to automatically quantify the IRF volume within a 6 mm × 6 mm OCT scan at baseline and at the last follow-up.The correlation of visual acuity with IRF volume,central subfield thickness(CST),disorganization of the retinal inner lay-ers(DRIL),hyperreflective foci(HRF),external limiting membrane(ELM),ellipsoid zone(EZ),and vitreomacular in-terface abnormality(VMIA)was analyzed at baseline and the last follow-up.Additionally,the correlation of IRF volume with CST,DRIL,HRF,ELM,EZ,and VMIA was analyzed at both time points.Furthermore,the correlation of the visual acuity at the last follow-up with the IRF volume,CST,DRIL,HRF,ELM,EZ,and VMIA at baseline was analyzed.Results Compared with the baseline value,patients exhibited a significant increase in the best corrected visual acuity(BCVA)(logMAR),a significant decrease in the IRF volume and CST,a significant reduction in the HRF,a significant re-covery in the DRIL,ELM,and EZ(all P＜0.05),and no significant changes in the VMIA(P=1.000)at the last follow-up.At baseline,the BCVA was negatively correlated with the IRF volume,CST,DRIL,and HRF,but positively correlated with the ELM and EZ(all P＜0.05);there was no correlation between the BCVA and VMIA(P=0.069).At the last follow-up,the BCVA was negatively correlated with the DRIL,HRF,and VMIA,but positively correlated with the ELM and EZ(all P＜0.01);the BCVA did not correlate with the IRF volume and CST(P=0.419 and 0.994).At baseline,the IRF volume was positively correlated with the CST(P＜0.001)but negatively correlated with the ELM and EZ(P＜0.01);the IRF vol-ume did not correlate with the DRIL,HRF,and VMIA(all P＞0.05).At the last follow-up,the IRF volume was positively correlated with the CST and HRF(all P＜0.01);however,it was not correlated with the DRIL,ELM,EZ,and VMIA(all P＞0.05).The BCVA at the last follow-up was positively correlated with the BCVA,ELM,and EZ at baseline,but negative-ly correlated with the IRF volume,CST,DRIL,HRF,and VMIA at baseline(all P＜0.05).Conclusion The baseline IRF volume in DME patients is an important influencing factor of visual acuity at baseline and the last follow-up.Hence,the IRF volume may serve as a potential biomarker in the management of DME.

Objective:To evaluate the topological alterations of resting-state brain networks in patients with idiopathic generalized epilepsy with generalized tonic-clonic seizure (IGE-GTCS) using minimum spanning tree (MST) based on graph theoretic analysis, and to further analyze the relationships between topological features, duration, and antiepileptic drug response.Methods:This study was a cross-sectional study. Retrospectively, 75 IGE-GTCS patients and 37 healthy controls (HC) who underwent brain MR imaging at the Affiliated of Nanjing University Medical School Drum Tower Hospital from January 2013 to December 2020 were enrolled. IGE-GTCS patients were grouped into well-controlled subgroup (WC; n=55) and drug-resistant subgroup (DR; n=20) according to their response to antiepileptic drugs. Firstly, the time series correlations between 116 regions of the whole brain of each subject were calculated to construct functional connectivity matrices. For each functional connectivity matrix, the Kruskal algorithm was used to MST, and the topological metrics of each MST were calculated, including leaf fraction, tree hierarchy, and diameter. The comparison of MST topological metrics between the two groups was performed using two-sample t-test. Pearson correlation analysis was used to calculate the correlation between disease duration and MST metrics in the WC subgroup and the DR subgroup. Results:Compared with the HC group, the MST leaf fraction ( t=2.27, P=0.025) increased in the IGE-GTCS patient group, and the diameter decreased ( t=-2.24, P=0.027), there was no statistically significant difference in tree hierarchy between IGE-GTCS patient group and HC group ( t=0.98, P=0.328). The MST leaf fraction ( t=-2.39, P=0.019) and tree hierarchy ( t=-2.24, P=0.027) in the WC subgroup was decreased compared with the DR subgroup, while there was no statistically significant difference in diameter between WC subgroup and DR subgroup ( P=0.093). The correlation analysis showed the MST diameter in WC subgroup was significantly correlated with disease duration ( r=0.452, P<0.001), while the MST diameter in DR subgroup was not significantly correlated with disease duration ( r=-0.062, P=0.847). Conclusions:Patients with IGE-GTCS exhibit specific alterations in the global topology of brain network, characterized by increased centralization and efficiency. The effective antiepileptic drug treatment is associated with a recovery of brain network abnormalities.

Objective:To investigate the iodine nutrition status of pregnant women in Zhejiang Province, explore the impact of salt industry system reform on iodine nutrition level of pregnant women, and provide scientific basis for prevention and treatment of iodine deficiency disorders.Methods:From 2016 to 2021, a multi-stage stratified sampling method was used to select 100 pregnant women from 90 counties (cities, districts) in Zhejiang Province each year as survey subjects. Salt samples were collected from pregnant women's families, and one random urine sample was taken for salt iodine and urinary iodine level testing, respectively.Results:A total of 56 581 samples of household edible salt were collected from pregnant women, with a median salt iodine level of 23.20 mg/kg. Among them, 7 961 were non iodized salt, 45 803 were qualified iodized salt, and 2 817 were unqualified iodized salt. The iodized salt coverage rate was 85.93% (48 620/56 581), and the qualified iodized salt consumption rate was 80.95% (45 803/56 581). The proportion of non iodized salt increased from 10.05% (897/8 928) in 2016 to 15.09% (1 461/9 679) in 2021 (χ 2trend = 95.16, P < 0.001). A total of 56 581 urine samples were collected from pregnant women, with a median urinary iodine level of 130.50 μg/L. Among them, the proportions of urinary iodine levels < 150, 150 - 249, 250 - 499, and ≥500 μg/L were 58.32% (32 996/56 581), 27.24% (15 410/56 581), 12.24% (6 926/56 581), and 2.21% (1 249/56 581), respectively. The median urinary iodine level of pregnant women in inland areas was significantly higher than that in coastal areas ( Z = 19.15, P < 0.001). Furthermore, urinary iodine levels exhibited a non-linear decline as age increased (χ 2regression = 12.65, P < 0.001; χ 2partial = 22.65, P < 0.001) and as pregnancy progressed (χ 2regression = 37.28, P < 0.001; χ 2partial = 18.89, P < 0.001). Conclusions:The overall iodine nutrition status of pregnant women in Zhejiang Province is in a state of iodine deficiency (< 150 μg/L), and there is a greater risk in coastal areas compared to inland areas. However, in the context of the reform of the salt industry system, it is still necessary to strengthen the quality supervision of iodized salt, provide scientific iodine supplementation education, promote specialized iodized salt for pregnant women, and strengthen interventions for prevention and control of iodine deficiency disorders.

Cysteine protease inhibitor SN(Cystatin SN , CST1), a member of the type 2 cystatins superfamily, regulates tumor biological activities by modulating cysteine protease activity. CST1 is abnormally expressed in digestive system neoplasms, such as esophageal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer. CST1 influences tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through signaling pathways including Wnt, STAT3, and PI3K-AKT. Its expression levels significantly correlated with tumor stage, metastasis, and patient prognosis, suggesting its potiential as a novel biomarker for early diagnosis, therapeutic evaluation, and prognosis in digestive system neoplasms. This article systematically reviews the molecular characteristics of CST1, its mechanisms of action in digestive system neoplasms, clinical significance, and explores its potential as a therapeutic target.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective:Evaluate To evaluate the efficacy of eccentric mixing in correcting EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) and platelet (PLT) count.Methods:A case-control study was conducted using EDTA-PTCP patient samples collected from the First Affiliated Hospital of Harbin Medical University from April 1st, 2024, to December 27th, 2024, including 82 cases with mean age 57.98±17.28 years old. EDTA-PTCP was defined as PLT≥3 under microscopy. Samples underwent eccentric mixing at 500 r/min or 3000 r/min for durations ranging from 0.5 to 13 minutes to determine the optimal PLT disaggregation protocol. Repeated-measures ANOVA and paired t-tests were used to analyze PLT results. While chi-square tests were used to compare effective disaggregation rates under the optimal eccentric mixing method and sodium citrate anticoagulation. Statistical significance was defined as P<0.05. Results:Eccentric mixing at 3000 r/min for 10 minutes significantly elevated PLT counts to (135.6±63.91)×10 9/L, compared with untreated group (47.72±25.47)×10 9/L ( t=5.74, P<0.001). Blood analyzer showed that 3000 r/min for 10 minutes method did not alter red blood cell (4.32±0.76 vs. 4.27±0.75)×10 12/L nor white blood cell (6.17±2.22 vs. 6.36±2.14)×10 9/L counts compared with untreated group, in which red blood cell (4.27±0.75)×10 12/L ( t=0.40, P=0.690) and white blood cell(6.36±2.14)×10 9/L ( t=0.48, P=0.630). The eccentric mixing achieved a disaggregation rate of 92.68% while sodium citrate anticoagulation 63.41%, with significant differenct (χ2=20.5, P<0.001). Conclusion:Eccentric mixing at 3000 r/min for 10 minutes effectively disaggregates platelets in EDTA-PTCP, correcting PLT counts without affecting other blood cells. This technique outperforms anticoagulant replacement strategies, offering a more efficient solution for clinical use as an alternative for changing anticoagulant.