OBJECTIVES: Neuropathic pain (NP) is one of the most common forms of chronic pain, yet current treatment options are limited in effectiveness. Peripheral nerve injury activates spinal microglia, altering their inflammatory response and phagocytic functions, which contributes to the progression of NP. Most current research on NP focuses on microglial inflammation, with relatively little attention to their phagocytic function. Early growth response factor 2 (EGR2) has been shown to regulate microglial phagocytosis, but its specific role in NP remains unclear. This study aims to investigate how EGR2 modulates microglial phagocytosis and its involvement in NP, with the goal of identifying potential therapeutic targets. METHODS: Adult male Sprague-Dawley (SD) rats were used to establish a chronic constriction injury (CCI) model of the sciatic nerve. Pain behaviors were assessed on days 1, 3, 7, 10, and 14 post-surgery to confirm successful model induction. The temporal and spatial expression of EGR2 in the spinal cord was examined using real-time quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. Adeno-associated virus (AAV) was used to overexpress EGR2 in the spinal cord, and behavioral assessments were performed to evaluate the effects of EGR2 modulation of NP. CCI and lipopolysaccharide (LPS) models were established in animals and microglial cell lines, respectively, and changes in phagocytic activity were measured using RT-qPCR and fluorescent latex bead uptake assays. After confirming the involvement of microglial phagocytosis in NP, AAV was used to overexpress EGR2 in both in vivo and in vitro models, and phagocytic activity was further evaluated. Finally, eukaryotic transcriptome sequencing was conducted to screen differentially expressed mRNAs, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify potential downstream effectors of EGR2. RESULTS: The CCI model successfully induced NP. Following CCI, EGR2 expression in the spinal cord was upregulated in parallel with NP development. Overexpression of EGR2 via spinal AAV injection enhanced microglial phagocytic activity and increased pain hypersensitivity in rats. Both animal and cellular models showed that CCI or LPS stimulation enhanced microglial phagocytosis, which was further amplified by EGR2 overexpression. Transcriptomic analysis of spinal cord tissues from CCI rats overexpressing EGR2 revealed upregulation of numerous genes associated with microglial phagocytosis and pain regulation. Among them, Lag3 emerged as a potential downstream target of EGR2. CONCLUSIONS EGR2 contributes to the maintenance of NP by enhancing microglial phagocytosis in the spinal dorsal horn.
Animals ; Microglia/metabolism* ; Phagocytosis/physiology* ; Rats, Sprague-Dawley ; Neuralgia/physiopathology* ; Early Growth Response Protein 2/metabolism* ; Male ; Rats ; Spinal Cord/metabolism* ; Sciatic Nerve/injuries*

Objective:To analyze the current status and factors influencing clinician participation in remote patient management in China.Methods:In December 2023, a structured electronic questionnaire was administered to 7 980 clinicians, including 930 cardiologists. The survey assessed clinicians′ participation in online doctor-patient interactions; differences in hospital support across city tiers, hospital grades, professional titles, and departments; and factors influencing the willingness of clinicians to invest time in remote patient management.Results:Among the 7 980 surveyed clinicians, online consultations had the highest participation rate (72.2%). Among cardiologists, participation rates for online consultations, health education, and post-consultation management were 73.3%, 66.9%, and 38.5%, respectively, which were relatively higher than those of other specialties. Hospital-based support for physicians in remote patient management showed significant variations across specialties and regions. Among cardiologists, 68.4% received "encouraging" policies, with the majority falling under "encouragement without incentive policies" (42.6%). In tier 3 cities, the proportion of physicians receiving "encouragement without incentive policies" was the highest (47.9%), while the proportion in the "cautious, requiring reporting" category was the lowest (3.9%). During remote patient management, the proportions of clinicians receiving support from professional teams were highest among those in tier 3 cities (29.6%) and cardiologists (30.5%). A significant interaction effect was observed between hospital policy and specialty (cardiologists vs. all clinicians) regarding physicians′ willingness to invest time in remote patient management ( F=5.95, P<0.001). Among cardiologists, those working in institutions with "encouraging, with incentives" policies reported a significantly longer median weekly investment time (10.0 h) compared to those under "neutral, unrestricted" policies (7.0 h, P<0.001). Cardiologists with team support reported a significant increase in the time they were willing to invest (10 h/week) than those without team support (7.0 h/week, P<0.001), although no significant interaction effect was found when compared with all clinicians ( P=0.186). Cardiologists with a high online income (>5 000 Yuan/month) reported a significantly longer weekly investment time in remote management (25.0 h) compared to those with lower income (<200 yuan/month; 8.0 h, P<0.001). However, whether the income met their personal expectations had no significant effect on their time commitment ( P=0.638). Conclusions:Clinicians from tertiary hospitals and tier 3 cities demonstrated a higher level of engagement in remote patient management. Strengthening hospital policy support, enhancing team-based collaborations, and increasing online income levels may help promote the broader adoption of telemedicine.

Objective:To investigate the current awareness of large language models (LLM) among Chinese clinical physicians and analyze the application needs of cardiovascular specialists.Methods:This is a cross-sectional study utilized convenience sampling. In December 2023, a self-designed questionnaire was distributed to 7 980 clinical physicians, including 930 cardiologists. The survey collected demographic information, including work city (categorized as first-tier, new first-tier, second-tier, third-tier, and fourth-tier and below), hospital level, professional title, and department. And the awareness of LLM, and their application demands in clinical decision-making support, information filtering, and scientific research work were also collected. Differences in awareness and application requirements across geographic regions, hospital tiers, professional ranks, and medical departments were analyzed. Besides, specific demands of cardiovascular specialists were further examined.Results:Among the 7 980 clinical physicians, the awareness rate of LLM was 76.3% (6 088/7 980), and the utilization rate was 11.8% (942/7 980). For the 930 cardiologists, the awareness rate was 78.5% (730/930) and the utilization rate was 11.4% (106/930). Significant differences in awareness and utilization rates were observed across city tiers, hospital grades, and departments (all P<0.05). No significant difference was found among professional titles ( P=0.053). Among the 6 088 physicians aware of LLM, demand rates for clinical information filtering, clinical decision support, and research assistance were 87.3% (5 312/6 088), 78.4% (4 774/6 088), and 75.8% (4 616/6 088), respectively. For the 730 cardiologists aware of LLM, these rates were 91.0% (664/730), 79.2% (578/730), and 75.9% (554/730), respectively. Significant differences in demands for clinical information filtering and research assistance were observed across city tiers, hospital grades, professional titles, and departments (all P<0.05), while no significant difference was noted for decision support demands across hospital grades ( P=0.085). In clinical information screening and acquisition, cardiologists from different city tiers exhibited statistically significant differences in the demand for literature interpretation. Similarly, variations in the demand for conference summaries, expert biographies, healthcare policies, and social news were noted among cardiologists with different professional titles, while disparities in patient education and science popularization needs were identified across city tiers and hospital grades (all P<0.05). In clinical decision-making support, cardiologists from diverse city tiers and professional titles demonstrated distinct differences in guideline and consensus inquiries, and those from various city tiers showed varied demands for pharmaceutical and medical device-related content (all P<0.05). For research support, cardiologists across city tiers and professional titles exhibited statistically significant differences in trial protocol design requirements, while those from varying city tiers differed in literature search/analysis and research application procedures. Additionally, physicians from different hospital grades displayed divergent needs for data collection (all P<0.05). Conclusions:The adoption of LLM is significantly influenced by regional disparities, institutional resources, and professional backgrounds. Implementing targeted interventions, such as enhancing technical training, optimizing LLM functionalities, and improving accessibility across diverse healthcare settings, could encourage widespread integration of LLM into clinical practice. Such measures could ultimately enhance the quality and efficiency of medical services in China and foster innovations in healthcare delivery.

Objective To analyze the effect of LINC00894 on the malignant biological behavior of liver cancer cells by regulating the microRNA(miR)-495-3p/RAS associated binding protein 23(Rab23)axis.Methods Cancer and adjacent tissues of 53 patients with liver cancer who undergoing surgery from January 2023 to November 2023 were collected.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of LINC00894,miR-495-3p and Rab23 in tissues and in vitro cultured cells Huh7,SMMC-7721,HepG2 and L-02.Cells Huh7 were randomly separated into Huh7 group,NC group,si-LINC00894 group,anti-NC group,and anti-miR-495-3p group.CCK-8,flow cytometry and Transwell were used to compare the cell proliferation,apoptosis,migration and invasion of each group.Western blot was used to detect the expression of Rab23 and proliferation-related proteins in cells.The relationship between LINC00894 and miR-495-3p,miR-495-3p and Rab23 was analyzed and verified by dual luciferase reporter gene assay.Results The mRNA and protein expression of LINC00894 and Rab23 were higher in cancer tissues and cells of liver cancer patients,while the mRNA expression of miR-495-3p was lower(P＜0.05).The apoptosis rate of si-LINC00894 group was higher than that of Huh7 group and NC group,and the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells were lower than those in Huh7 group and NC group(P＜0.05);the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells in the anti-miR-495-3p group were higher than those in the anti-NC group and si-LINC00894 group,the apoptosis rate of cells was lower than that in the anti NC group and si-LINC00894 group(P＜0.05).The luciferase activity in the WT-LINC00894+miR-495-3p group was lower than that in the WT-LINC00894+miR-NC group(P＜0.05),the luciferase activity in the WT-Rab23+miR-495-3p group was lower than that in the WT-Rab23+miR-NC group(P＜0.05).Conclusion Downregulation of LINC00894 can promote the expression of miR-495-3p,inhibit the expression of Rab23,and thus exert the inhibitory effect on the malignant biological behavior of liver cancer cells.

Objective To analyze the effect of LINC00894 on the malignant biological behavior of liver cancer cells by regulating the microRNA(miR)-495-3p/RAS associated binding protein 23(Rab23)axis.Methods Cancer and adjacent tissues of 53 patients with liver cancer who undergoing surgery from January 2023 to November 2023 were collected.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of LINC00894,miR-495-3p and Rab23 in tissues and in vitro cultured cells Huh7,SMMC-7721,HepG2 and L-02.Cells Huh7 were randomly separated into Huh7 group,NC group,si-LINC00894 group,anti-NC group,and anti-miR-495-3p group.CCK-8,flow cytometry and Transwell were used to compare the cell proliferation,apoptosis,migration and invasion of each group.Western blot was used to detect the expression of Rab23 and proliferation-related proteins in cells.The relationship between LINC00894 and miR-495-3p,miR-495-3p and Rab23 was analyzed and verified by dual luciferase reporter gene assay.Results The mRNA and protein expression of LINC00894 and Rab23 were higher in cancer tissues and cells of liver cancer patients,while the mRNA expression of miR-495-3p was lower(P＜0.05).The apoptosis rate of si-LINC00894 group was higher than that of Huh7 group and NC group,and the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells were lower than those in Huh7 group and NC group(P＜0.05);the absorbance at 24 h,48 h,and 72 h,numbers of migrating and invading cells,and expression of Rab23 in cells in the anti-miR-495-3p group were higher than those in the anti-NC group and si-LINC00894 group,the apoptosis rate of cells was lower than that in the anti NC group and si-LINC00894 group(P＜0.05).The luciferase activity in the WT-LINC00894+miR-495-3p group was lower than that in the WT-LINC00894+miR-NC group(P＜0.05),the luciferase activity in the WT-Rab23+miR-495-3p group was lower than that in the WT-Rab23+miR-NC group(P＜0.05).Conclusion Downregulation of LINC00894 can promote the expression of miR-495-3p,inhibit the expression of Rab23,and thus exert the inhibitory effect on the malignant biological behavior of liver cancer cells.

Objective:To analyze the current status and factors influencing clinician participation in remote patient management in China.Methods:In December 2023, a structured electronic questionnaire was administered to 7 980 clinicians, including 930 cardiologists. The survey assessed clinicians′ participation in online doctor-patient interactions; differences in hospital support across city tiers, hospital grades, professional titles, and departments; and factors influencing the willingness of clinicians to invest time in remote patient management.Results:Among the 7 980 surveyed clinicians, online consultations had the highest participation rate (72.2%). Among cardiologists, participation rates for online consultations, health education, and post-consultation management were 73.3%, 66.9%, and 38.5%, respectively, which were relatively higher than those of other specialties. Hospital-based support for physicians in remote patient management showed significant variations across specialties and regions. Among cardiologists, 68.4% received "encouraging" policies, with the majority falling under "encouragement without incentive policies" (42.6%). In tier 3 cities, the proportion of physicians receiving "encouragement without incentive policies" was the highest (47.9%), while the proportion in the "cautious, requiring reporting" category was the lowest (3.9%). During remote patient management, the proportions of clinicians receiving support from professional teams were highest among those in tier 3 cities (29.6%) and cardiologists (30.5%). A significant interaction effect was observed between hospital policy and specialty (cardiologists vs. all clinicians) regarding physicians′ willingness to invest time in remote patient management ( F=5.95, P<0.001). Among cardiologists, those working in institutions with "encouraging, with incentives" policies reported a significantly longer median weekly investment time (10.0 h) compared to those under "neutral, unrestricted" policies (7.0 h, P<0.001). Cardiologists with team support reported a significant increase in the time they were willing to invest (10 h/week) than those without team support (7.0 h/week, P<0.001), although no significant interaction effect was found when compared with all clinicians ( P=0.186). Cardiologists with a high online income (>5 000 Yuan/month) reported a significantly longer weekly investment time in remote management (25.0 h) compared to those with lower income (<200 yuan/month; 8.0 h, P<0.001). However, whether the income met their personal expectations had no significant effect on their time commitment ( P=0.638). Conclusions:Clinicians from tertiary hospitals and tier 3 cities demonstrated a higher level of engagement in remote patient management. Strengthening hospital policy support, enhancing team-based collaborations, and increasing online income levels may help promote the broader adoption of telemedicine.

Objective:To investigate the current awareness of large language models (LLM) among Chinese clinical physicians and analyze the application needs of cardiovascular specialists.Methods:This is a cross-sectional study utilized convenience sampling. In December 2023, a self-designed questionnaire was distributed to 7 980 clinical physicians, including 930 cardiologists. The survey collected demographic information, including work city (categorized as first-tier, new first-tier, second-tier, third-tier, and fourth-tier and below), hospital level, professional title, and department. And the awareness of LLM, and their application demands in clinical decision-making support, information filtering, and scientific research work were also collected. Differences in awareness and application requirements across geographic regions, hospital tiers, professional ranks, and medical departments were analyzed. Besides, specific demands of cardiovascular specialists were further examined.Results:Among the 7 980 clinical physicians, the awareness rate of LLM was 76.3% (6 088/7 980), and the utilization rate was 11.8% (942/7 980). For the 930 cardiologists, the awareness rate was 78.5% (730/930) and the utilization rate was 11.4% (106/930). Significant differences in awareness and utilization rates were observed across city tiers, hospital grades, and departments (all P<0.05). No significant difference was found among professional titles ( P=0.053). Among the 6 088 physicians aware of LLM, demand rates for clinical information filtering, clinical decision support, and research assistance were 87.3% (5 312/6 088), 78.4% (4 774/6 088), and 75.8% (4 616/6 088), respectively. For the 730 cardiologists aware of LLM, these rates were 91.0% (664/730), 79.2% (578/730), and 75.9% (554/730), respectively. Significant differences in demands for clinical information filtering and research assistance were observed across city tiers, hospital grades, professional titles, and departments (all P<0.05), while no significant difference was noted for decision support demands across hospital grades ( P=0.085). In clinical information screening and acquisition, cardiologists from different city tiers exhibited statistically significant differences in the demand for literature interpretation. Similarly, variations in the demand for conference summaries, expert biographies, healthcare policies, and social news were noted among cardiologists with different professional titles, while disparities in patient education and science popularization needs were identified across city tiers and hospital grades (all P<0.05). In clinical decision-making support, cardiologists from diverse city tiers and professional titles demonstrated distinct differences in guideline and consensus inquiries, and those from various city tiers showed varied demands for pharmaceutical and medical device-related content (all P<0.05). For research support, cardiologists across city tiers and professional titles exhibited statistically significant differences in trial protocol design requirements, while those from varying city tiers differed in literature search/analysis and research application procedures. Additionally, physicians from different hospital grades displayed divergent needs for data collection (all P<0.05). Conclusions:The adoption of LLM is significantly influenced by regional disparities, institutional resources, and professional backgrounds. Implementing targeted interventions, such as enhancing technical training, optimizing LLM functionalities, and improving accessibility across diverse healthcare settings, could encourage widespread integration of LLM into clinical practice. Such measures could ultimately enhance the quality and efficiency of medical services in China and foster innovations in healthcare delivery.

Objective:To investigate the effects of Apelin-13 regulatory peptide on neuronal cell pyroptosis in mice modeled with cerebral ischemia-reperfusion(I/R).Methods:We prepared a mouse cerebral I/R model using middle cerebral artery embolization and Reperfusion(MCAO/R).The HT22 cell injury model was prepared by the oxygen glu-cose deprivation/reoxygenation(OGD/R),and Apelin-13 treatment was also given.Neurological function was assessed by neurological deficit score;hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphologic changes of the infarcted area of the mice;and 2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;The expression of NOD-like receptor thermoprotein structural domain-related protein 3(NLRP3),gasdermin D(GSDMD),caspase-1,apoptosis-associated speck-like protein(ASC),interleukin 1β(IL-1β),and interleukin 18(IL-18)in brain tissues from infarcted areas or HT22 cells was detected by Western Blot,and IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA)in serum of mice and culture supema-tants;The cell viability and cell damage of HT22 were detected by CCK-8 kit and lactate dehydrogenase(LDH)assay kit,respectively;caspase-1 activity was measured by caspase-1 activity kit in HT22 cells;and the expression of caspase-1 and GSDMD was observed by immunofluorescence staining in HT22 cells.Results:Apelin-13 significantly improved neurological function and cerebral infarct volume in I/R mice,and attenuated pathological damage in the in-farcted area.It also reduced the serum levels of IL-1β and IL-18.In addition,Apelin-13 reduced the expression of mol-ecules such as NLRP3,GSDMD,caspase-1,IL-1β,and IL-18 in the cerebral infarct area of mice.In vitro experiments showed that Apelin-13 significantly increased the viability of OGD/R-treated HT22 cells,decreased caspase-1 activity,and reduced the LDH content,as well as decreased the expression of molecules such as NLRP3,GSDMD,caspase-1,IL-1β,IL-18,and so on,in OGD/R-treated HT22 cells.Conclusion:Apelin-13 inhibits pyroptosis through the NL-RP3/caspase-1/GSDMD pathway in cerebral ischemia/reperfusion mice and thus exerts neuroprotective effects.

Objective:To investigate whether Lycium barbarum polysaccharides(LBP)can inhibit ferroptosis through the solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4)pathway and thus alleviate cerebral ischemia-reperfusion(I/R)injury.Methods:The mouse model of cerebral I/R injury was established by mid-dle cerebral artery occlusion(MCAO)and treated with Lycium barbarum polysaccharides(LBP).The mice were ran-domly divided into three groups:sham group,I/R group,and I/R+LBP group.2,3,5triphenyltetrazolium chloride(TTC)staining was used to observe the volume of cerebral infarcts;Neurological function was assessed by neurological deficit score;The superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA),and Fe2+detection kit to detect the changing levels of SOD,GSH,MDA,and Fe2+;Western Blot detects the expression of ferroptosis-related keys GPX4,SLC7A11,and Nrf2.Results:LBP can reduce the cerebral infarction volume and improve the neurological function.LBP increases the content of SOD and GSH and reduces the content of MDA in I/R injured mice.Western Blot results show that the expression levels of ferroptosis-related proteins GPX4,SLC7A11,and Nrf2 in the brain tissue of the I/R group were significantly lower than those of the Sham group.After LBP treatment,the levels of GPX4,SLC7A11,and Nrf2 in the LBP+I/R group were significantly higher than those of the I/R group.Conclusion:LBP at-tenuates cerebral I/R injury by inhibiting ferroptosis through the SLC7A11/GPX4 pathway.LBP has a neuroprotective effect on cerebral I/R injury and is a potential neuroprotective agent.

As a new clinical trial mode,decentralized & digitalized clinical trial(DCT)is based on digital health equipment and uses internet and artificial intelligence technologies to complete the screening,registration,randomization,intervention,evaluation and follow-up of subjects,which is helpful to improve efficiency and reduce trial costs.The DCT mode has been applied to evaluate the treatment and management effects of cardiovascular diseases such as atrial fibrilla-tion,heart failure,coronary heart disease,and hypertension,showing broad development prospects and application space.This article will provide a brief introduction to representative DCT in the global cardiovascular disease field,and look for-ward to the application prospects of this model,providing reference and guidance for accelerating the development of cardio-vascular DCT in China.