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 improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective To evaluate the efficacy of hypothermia therapy in neonates with hypoxic-ischemic encephalopathy(HIE)through the analysis of amplitude-integrated electroencephalography.Methods A retrospective analysis was conducted on 59 neonates with moderate to severe HIE.They were divided into observation group(n=31,hypothermia therapy)and control group(n=28,conventional therapy)according to different treatment protocols.Chi-square test,independent sample t-test,and one-factor Mann-Whitney U test were used for intergroup difference analysis.Results Significant differences between two groups were observed in lower boundary amplitude after 24 h of treatment,sleep-awake cycle after 72 h of treatment,and total scores after 72 h of treatment(P<0.05).After 48 and 72 h of treatment,the neonates in hypothermia therapy group had obviously lower neuro-specific enolase level than those in control group(P<0.05).Conclusion Early application of hypothermia therapy can significantly improve cerebral function in neonates with HIE and lower the neuro-specific enolase level.

Objective:To design a programmed evaluation process,and to explore its application effect in the management of medical equipment in emergency department.Methods:The information management platform was constructed based on IntelliJ IDEA and Java language with browser and server(B/S)architecture,a programmed evaluation process was designed to manage medical equipment in the emergency department.From 2021 to 2022,27 medical devices in use in the emergency department of Beijing Friendship Hospital,Capital Medical University were selected,the programmed evaluation process and the post-evaluation process were adopted respectively for management according to the different equipment management methods.A total of 800 equipment operation logs sampled were analyzed under the two management methods.The timeliness of equipment management,management effect and satisfaction scores of related management personnel were compared between the two management methods.Results:The average time consumption of equipment warning timeliness,timeliness of maintenance personnel's arrival and timeliness of proposed treatment methods in the programmed evaluation process management were(0.92±0.21)min,(5.43±1.08)min and(15.63±2.27)min,respectively,which were lower than those in post-evaluation process management method,the difference was statistically significant(t=13.810,16.893,16.554,P＜0.05).The failure rate of 400 logs sampled by the programmed evaluation process management method was 2.75%(11/400),which was lower than that of the post-evaluation process management method,the regular maintenance completion rate was 99.75%(399/400),which was higher than that of the post-evaluation process management method,the difference was statistically significant(x2=18.841,10.778,P＜0.05).The equipment maintenance time and equipment maintenance cost of the programmed evaluation process management were(9.32±1.18)days and CNY(201,600±50,500),respectively,which were lower than those of the post-evaluation process management method,and the difference was statistically significant(t=12.663,37.213,P＜0.05).The satisfaction scores of maintenance engineers,medical staff and patients in equipment use management for the programmed evaluation process management were(97.25±2.44),(98.63±4.57)and(97.16±3.09),respectively,which were higher than the post-evaluation process management method,and the differences were statistically significant(t=21.284,8.206,5.933,P＜0.05).Conclusion:The application of programmed evaluation process to the equipment management of emergency department of the hospital can effectively improve and make up for the loopholes and deficiencies in the conventional equipment management,improve the effect of equipment management,reduce the frequency of equipment failure,and ensure the safe and stable operation of equipment.

To summarize the nursing experience of a patient with intestinal fistula after laparoscopic extended radical resection of rectal cancer plus ileostomy.Nursing points include:multi-disciplinary joint formulation of systemic treatment and nursing plan;using fistula isolation technology to isolate and drain digestive fluid;implementing incision segmentation management to promote infection control and tissue growth.After careful treatment and nursing care,the intestinal fistula was closed after 38 days of surgery,and the wound healed after 52 days of surgery.

Immunotherapy has made breakthrough in the field of tumor treatment. How to accurately predict the response of tumor patients to immunotherapy in the early stage is currently a clinical challenge. Nuclear medicine molecular imaging provides a new technological means for early accurate diagnosis, treatment monitoring, early warning of recurrence and metastasis, and guidance for personalized treatment of diseases. Therefore, it plays an irreplaceable role in precise diagnosis and treatment of tumors and patient stratification. This article reviews the progress of molecular imaging research on immune cells and related targets within the tumor microenvironment.

Objective·To explore the effect of online courses combined with the teach-back method among patients with laryngectomy and their family caregivers.Methods·Convenience sampling was used to select patients with laryngectomy treated in the Department of Otolaryngology,Shanghai Changhai Hospital from July 2022 to June 2023 and their family caregivers.The participants were divided into a control group and an observation group using the random number table method.The intervention was conducted in two different wards.General information of the two groups of patients and caregivers was collected.After admission,the control group watched offline videos recorded by the department.The videos introduced laryngocarcinoma-related knowledge and standard procedures of airway stoma care,suctioning,nasal feeding,etc.,which were divided into 4 sessions with 30 min each.The patients watched one session per week.The observation group watched the same videos(8 lessons)online on their own after admission,while the nursing staff used the teach-back method for health education,consolidating 2 lessons once a week,45 min/session for 4 weeks.The effectiveness of the intervention was evaluated by using Caregiver Preparedness Scale(CPS),Family Caregiver Task Inventory(FCTI),and Chinese Quality of Life Instruments for Cancer Patients-Head and Neck Cancer(QLICP-HN)at baseline(1st week),before discharge(4th week),and one month after discharge(8th week),as well as the incidence of adverse events during home care.Results·The study included a total of 120 pairs of patients and caregivers,with 60 pairs in each group.Five pairs in each group were excluded due to various reasons,leaving a total of 55 pairs in each group.There were no statistically significant differences between the two groups in terms of general information of the patients and the caregivers,QLICP-HN scores of the patients,and CPS and FCTI scores of the caregivers at baseline(P＞0.05).Before discharge and 1 month after discharge,the CPS scores of the caregivers and the QLICP-HN scores of the patients in the observation group were significantly higher than those in the control group,and the FCTI scores were significantly lower(lower scores indicating better nursing care),with statistically significant differences(P＜0.05).Within 1 month after discharge,the incidence of adverse home care events in the observation group was lower than that in the control group(5.5%vs 29.1%),and the difference was statistically significant(P＜0.05).Conclusion·The online courses combined with the teach-back method help improve the readiness to care and caregiving competence of family caregivers of post-laryngectomy patients,improve patients'quality of life,and reduce the incidence of adverse events during home care.

ObjectiveTo observe the effect of Hedysari Radix polysaccharide （HRP） on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription protein 3 （STAT3） signaling pathway in diabetic nephropathy db/db mice. MethodFifty db/db mice were randomly divided into model group， irbesartan group （irbesartan suspension， 22.75 mg·kg^-1）， and high-， medium-， and low-dose HRP groups （HRP suspension， 200， 100， 50 mg·kg^-1） according to the body weight， with 10 mice in each group. Another 10 C57BL/6 mice were assigned to the normal group. The mice were treated with corresponding drugs by gavage， while those in the normal group and the model group received distilled water at 5 mL·kg^-1. The mice in the six groups were administered once a day by gavage for 12 consecutive weeks. The uric acid （UA）， triglycerides （TG）， and total cholesterol （TC） were detected. Periodic acid-Schiff （PAS） staining and Masson staining were used to observe the pathological changes in kidney tissues. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the protein and mRNA expression levels of JAK2， STAT3， suppressor of cytokine signaling 3 （SOCS3）， and tumor necrosis factor-α （TNF-α） in the kidney. ResultAfter 12 weeks of treatment， compared with the normal group， the model group showed significant pathological ultrastructural changes in kidney tissues and increased UA， TG， and TC levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed improvement in pathological ultrastructure of kidney tissues and reduced UA， TG， and TC levels （P<0.05， P<0.01）. Compared with the normal group， the model group showed a decrease in SOCS3 protein and mRNA expression levels and an increase in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.01）. Compared with the model group， the high- and medium-dose HRP groups and the irbesartan group showed an increase in SOCS3 protein and mRNA expression levels and a decrease in JAK2， STAT3， and TNF-α protein and mRNA expression levels （P<0.05， P<0.01）. ConclusionHRP can alleviate renal damage in diabetic nephropathy to a certain extent， and its mechanism may be related to the inhibition of the activation of the JAK2/STAT3 signaling pathway.

Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.
Hydrogels/chemistry* ; Microfluidics/methods* ; Microspheres ; Regenerative Medicine ; Tissue Engineering/methods*