Dental pulp stem cells (DPSCs) are a type of adult stem cell with abundant sources, easy accessibility, multipotent differentiation potential, and low immunogenicity. In recent years, they have attracted considerable attention due to their promising applications in repairing neural tissue injuries. Under specific induction conditions, DPSCs can directly differentiate into neuron-like cells and exert neuroprotective, immunomodulatory, anti-inflammatory, and anti-apoptotic effects through the paracrine secretion of neurotrophic and immunomodulatory factors. DPSCs can also be combined with biomaterial scaffolds such as hydrogels, chitosan, and polylactic acid, thereby enhancing neural differentiation efficiency and regenerative outcomes. However, their clinical application in neural repair still faces challenges, including poor microenvironmental adaptability, low differentiation efficiency and controllability, immune rejection, difficulties in large-scale production and quality control, and a lack of standardized operational protocols. Future research should focus on optimizing the adaptability of DPSCs to the injury microenvironment, improving their neural differentiation efficiency, strengthening immune regulation to ensure the safety of allogeneic transplantation, establishing GMP-compliant cell preparation and quality control systems, and developing standardized clinical procedures combined with multicenter trials to validate efficacy, thereby promoting the efficient, safe, and reproducible clinical translation of DPSCs in neural regeneration. This review summarizes the research progress on the neural differentiation of DPSCs, with an emphasis on strategies and molecular mechanisms for promoting neural regeneration, the challenges in clinical translation, and future development directions, aiming to provide a theoretical basis for research on the neural differentiation of DPSCs.

Objective To investigate changes in the microRNA expression profiles of apoptotic vesicles(apoVs)derived from bone marrow mesenchymal stem cells(BMSCs)under a simulated negative pressure environment,and to provide a theoretical basis for understanding the mechanism by which mechanical stress microenvironments influence the progression of osteoarthritis.Methods A negative pressure cellular environment was established using a pressure-loading system.Cell viability and apoptosis were assessed via the CCK-8 assay,Western blotting,and Annexin V-FITC/PI double staining.ApoVs were isolated by differential centrifugation and characterized using transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blotting.Small RNA sequencing was performed using the HiSeq Single-End mode,and differential expression analysis of microRNAs was conducted using DESeq to screen for differentially expressed microRNAs.The differentially screened microRNAs were validated by real-time quantitative PCR.After treating BMSCs with inhibitors of these differentially expressed microRNAs,the effects of the screened microRNAs on BMSCs were detected.Results Compared to apoVs generated by BMSCs under STS chemical treatment,those produced under a-40 kPa pressure environment showed significantly upregulated miR-183-5p and downregulated miR-3473.GO and KEGG enrichment analyses revealed that these differentially expressed microRNAs affected cell activity and inflammatory responses through multiple signaling pathways.Inhibition of miR-183-5p and miR-3473 expression reduced the proliferative activity of BMSCs.After inhibiting miR-183-5p expression,the levels of inflammatory factors increased.Inhibition of miR-3473 expression did not alter the IL-6 expression level,but significantly increased the TNFα expression level.Conclusions MicroRNAs specifically expressed in BMSC-derived apoVs under negative pressure stimulation may act as critical mechanical signaling mediators,regulating inflammatory response processes to participate in the pathogenesis and progression of arthritis.

Objective To investigate changes in the microRNA expression profiles of apoptotic vesicles(apoVs)derived from bone marrow mesenchymal stem cells(BMSCs)under a simulated negative pressure environment,and to provide a theoretical basis for understanding the mechanism by which mechanical stress microenvironments influence the progression of osteoarthritis.Methods A negative pressure cellular environment was established using a pressure-loading system.Cell viability and apoptosis were assessed via the CCK-8 assay,Western blotting,and Annexin V-FITC/PI double staining.ApoVs were isolated by differential centrifugation and characterized using transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blotting.Small RNA sequencing was performed using the HiSeq Single-End mode,and differential expression analysis of microRNAs was conducted using DESeq to screen for differentially expressed microRNAs.The differentially screened microRNAs were validated by real-time quantitative PCR.After treating BMSCs with inhibitors of these differentially expressed microRNAs,the effects of the screened microRNAs on BMSCs were detected.Results Compared to apoVs generated by BMSCs under STS chemical treatment,those produced under a-40 kPa pressure environment showed significantly upregulated miR-183-5p and downregulated miR-3473.GO and KEGG enrichment analyses revealed that these differentially expressed microRNAs affected cell activity and inflammatory responses through multiple signaling pathways.Inhibition of miR-183-5p and miR-3473 expression reduced the proliferative activity of BMSCs.After inhibiting miR-183-5p expression,the levels of inflammatory factors increased.Inhibition of miR-3473 expression did not alter the IL-6 expression level,but significantly increased the TNFα expression level.Conclusions MicroRNAs specifically expressed in BMSC-derived apoVs under negative pressure stimulation may act as critical mechanical signaling mediators,regulating inflammatory response processes to participate in the pathogenesis and progression of arthritis.

Objective To construct a regional collaborative cloud-based treatment model treatment model for patients with severe road traffic injuries,and to preliminarily evaluate the differences in nursing timeliness indicators and outcomes.Methods The regional collaborative cloud-based treatment platform includes 4 ports,including public security traffic police,pre-hospital emergency center,regional trauma center triage,and regional trauma center resuscitation unit.This forms a standardized real-time interactive treatment process between regional medical services and police for patients with severe road traffic injuries.Using a concurrent control study design,241 patients with severe road traffic injuries admitted to the emergency department of a regional trauma center in Zhejiang Province from May 2022 to May 2024 were selected as the study subjects.Among them,120 patients treated with the regional real-time collaborative cloud-based treatment model were designated as an experimental group,while 121 patients treated with the original trauma care process were designated as a control group.The differences in timeliness indicators and outcomes between the 2 groups were compared.Results The study included 241 patients with severe trauma.After the application of the regional collaborative cloud-based treatment model,the time from the scene of the accident to the hospital,the proportion of information early waming,completion time of pre-examination and triage,waiting time of the trauma team,the time of the first CT,the length of multidisciplinary consultation,and the time for completing hospitalization procedures in the experimental group were shorter than those in the control group(P＜0.05),the proportion of information early waming in the experimental group was 100％(120/120),and the proportion of information early waming in the control group was 52.1％(63/121).The difference between the two groups was statistically significant(P＜0.001).The survival rate of the experimental group was 90.8％(109/120),and that of the control group was 86.0％(104/121).There was no significant difference between the two groups(x2=1.399,P=0.237).Conclusion The regional collaborative cloud-based treatment model improves the timeliness and standardization of the treatment of patients with severe road traffic injury,which has certain reference significance and promotion value.

To summarize the emergency nursing experience of 1 patient with neck suicide complicated with airway obstruction and hemorrhagic shock.Nursing points:to ensure airway safety and establish artificial airway;to optimize airway management and implement early sedation and wake-up;to control injury bleeding and limited fluid resuscitation;to establish a micro blood station in the emergency department and start a high-dose blood transfusion procedure;to carry out the refined target body temperature management to reduce complications;to optimize speech communication strategies and implement early psychological care.After 7 days of careful treatment and nursing,the patient's condition improved and recovered.After 2 months of follow-up,the patient recovered well.

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

Objective To construct a regional collaborative cloud-based treatment model treatment model for patients with severe road traffic injuries,and to preliminarily evaluate the differences in nursing timeliness indicators and outcomes.Methods The regional collaborative cloud-based treatment platform includes 4 ports,including public security traffic police,pre-hospital emergency center,regional trauma center triage,and regional trauma center resuscitation unit.This forms a standardized real-time interactive treatment process between regional medical services and police for patients with severe road traffic injuries.Using a concurrent control study design,241 patients with severe road traffic injuries admitted to the emergency department of a regional trauma center in Zhejiang Province from May 2022 to May 2024 were selected as the study subjects.Among them,120 patients treated with the regional real-time collaborative cloud-based treatment model were designated as an experimental group,while 121 patients treated with the original trauma care process were designated as a control group.The differences in timeliness indicators and outcomes between the 2 groups were compared.Results The study included 241 patients with severe trauma.After the application of the regional collaborative cloud-based treatment model,the time from the scene of the accident to the hospital,the proportion of information early waming,completion time of pre-examination and triage,waiting time of the trauma team,the time of the first CT,the length of multidisciplinary consultation,and the time for completing hospitalization procedures in the experimental group were shorter than those in the control group(P＜0.05),the proportion of information early waming in the experimental group was 100％(120/120),and the proportion of information early waming in the control group was 52.1％(63/121).The difference between the two groups was statistically significant(P＜0.001).The survival rate of the experimental group was 90.8％(109/120),and that of the control group was 86.0％(104/121).There was no significant difference between the two groups(x2=1.399,P=0.237).Conclusion The regional collaborative cloud-based treatment model improves the timeliness and standardization of the treatment of patients with severe road traffic injury,which has certain reference significance and promotion value.

The liver regenerative capacity is crucial for patients with end-stage liver disease following partial hepatectomy (PHx). The specific bacteria and mechanisms regulating liver regeneration post-PHx remain unclear. This study demonstrated dynamic changes in the abundance of Parabacteroides distasonis (P. distasonis) post-PHx, correlating with hepatocyte proliferation. Treatment with live P. distasonis significantly promoted hepatocyte proliferation and liver regeneration after PHx. Targeted metabolomics revealed a significant positive correlation between P. distasonis and β-hydroxybutyric acid (BHB), as well as hyodeoxycholic acid and 3-hydroxyphenylacetic acid in the gut after PHx. Notably, treatment with BHB, but not hyodeoxycholic acid or 3-hydroxyphenylacetic acid, significantly promoted hepatocyte proliferation and liver regeneration in mice after PHx. Moreover, STAT3 inhibitor Stattic attenuated the promotive effects of BHB on cell proliferation and liver regeneration both in vitro and in vivo. Mechanistically, P. distasonis upregulated the expression of fatty acid oxidation-related proteins, and increased BHB levels in the liver, and then BHB activated the STAT3 signaling pathway to promote liver regeneration. This study, for the first time, identifies the involvement of P. distasonis and its associated metabolite BHB in promoting liver regeneration after PHx, providing new insights for considering P. distasonis and BHB as potential strategies for promoting hepatic regeneration.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Objective:To evaluate the clinical value of holographic imaging-based digital localization technology in robot-assisted partial nephrectomy（RAPN）for the treatment of completely endophytic renal tumors.Methods:A retrospective analysis was conducted on the clinical data of 23 patients with completely endophytic renal tumors who underwent RAPN at the First Affiliated Hospital of Xiamen University between December 2022 and December 2024. Patients were divided into two groups based on the use of holographic imaging：the holographic imaging group（16 cases）and the conventional group（7 cases）. There was no statistically significant difference between the holographic imaging group and the conventional group in terms of age［（41.9 ± 13.4）years vs.（46.9 ± 13.4）years］，body mass index［（25.6 ± 4.8）kg/m2 vs.（24.7 ± 3.1）kg/m2］，maximum tumor diameter［（3.1 ± 0.9）cm vs.（3.0 ± 9.0）cm］，tumor volume［（13.2 ± 9.0）cm3 vs.（34.9 ± 9.9）cm3］，R.E.N.A.L. score［（9.4 ± 1.2）points vs.（9.9 ± 0.7）points］，PADUA score［（10.4 ± 0.7）points vs.（9.4 ± 0.7）points］，proportion of T 1a stage patients［12 cases（75.0%）vs. 6 cases（85.7%）］and preoperative serum creatinine［（67.4 ± 9.5）μmol/L vs.（78.0 ± 16.0）μmol/L］. In the holographic group，holographic models were reconstructed based on preoperative enhanced CT or MRI images and used for preoperative planning and intraoperative localization. In the conventional group，surgeons relied on preoperative CT or MRI images for cognitive fusion during RAPN. Perioperative parameters such as warm ischemia time，operative time，tumor localization time，positive surgical margin rate，and renal function were compared between the two groups. Results:The operative time in the holographic group was significantly shorter than that in the conventional group［（152.8 ± 12.9）min vs.（218.4 ± 105.5）min， P = 0.001］. Warm ischemia time［（26.9 ± 3.4）min vs.（30.7 ± 3.8）min， P < 0.001］，localization time［（4.2 ± 0.9）min vs.（8.9 ± 1.7）min， P < 0.001］，and estimated blood loss［（47.0 ± 17.7）ml vs.（128.6 ± 87.8）ml， P < 0.001］were also significantly lower in the holographic group. In the conventional group，one patient underwent radical nephrectomy，while no patient in the holographic imaging group required conversion to radical nephrectomy. No cases of positive surgical margins were identified in either group. Serum creatinine levels measured one month after surgery showed no statistically significant differences between the two groups［（79.5 ± 15.7）μmol /L vs.（104.9 ± 22.5）μmol /L］. Conclusions:The application of holographic imaging-based digital localization technology in RAPN for completely endophytic renal tumors significantly reduces operative time，localization time，warm ischemia time，and intraoperative blood loss. This technology improves surgical efficiency and success rates，offering distinct clinical advantages.