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*

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Oral cavity cancer is the most common type of head and neck squamous cell carcinoma,and patients with locally advanced can-cer are mainly treated via surgical resection,followed by adjuvant radiotherapy.However,over the past decade,therapeutic progress in loc-ally advanced oral cavity cancer has been limited,with the overall survival remaining below 50%.Although many studies have reported high tumor response rates with neoadjuvant chemotherapy and targeted therapy,these findings have not translated into enhanced patient sur-vival.Neoadjuvant immunotherapy has become a research hotspot owing to the success of immunotherapy with immune checkpoint inhib-itors for relapsed and metastatic head and neck squamous cell carcinoma cases,with many ongoing randomized controlled studies focusing on drug discovery.In this review,we discuss the relevant clinical studies and highlight the therapeutic advancements in neoadjuvant immun-otherapy for locally advanced oral cavity cancer.

Objective:To explore the relationship between amniotic fluid and peripheral blood inflammatory factors and the pregnancy outcomes after emergency cervical cerclage, and to identify effective indicators for predicting adverse pregnancy outcomes after the procedure.Methods:A case-control study was conducted, including pregnant women who were hospitalized at Sun Yat-sen Memorial Hospital, from January 1, 2013, to July 31, 2019, and underwent emergency cervical cerclage due to cervical dilatation at gestational age between 16 and 28 weeks. A total of 85 pregnant women who underwent amniocentesis for the detection of amniotic fluid inflammatory factors during the perioperative period were included. Based on whether their baby was perinatal death, the participants were divided into the case group (28 cases with perinatal death) and the control group (57 cases with live births). Univariate logistic regression analysis was performed to identify risk factors associated with adverse pregnancy outcomes, followed by multivariate logistic regression analysis to establish a regression model and nomogram.Results:(1) The levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10 in the amniotic fluid during the perioperative period and postoperative serum C-reactive protein (CRP) were significantly higher in the case group compared to the control group (all P<0.05). The case group underwent emergency cervical cerclage at an earlier gestational age compared to the control group, and their cervical dilation was greater than that of the control group (all P<0.05). However, there were no significant differences in the white blood cell counts, neutrophil percentage, and the level of preoperative CRP in the peripheral blood of pregnant women during the perioperative period (all P>0.05). (2) Univariate logistic regression analysis showed that the levels of amniotic fluid WBC, TNF-α, IL-1β, IL-2 receptor (IL-2R), IL-6, IL-8, IL-10, postoperative CRP in the peripheral blood, gestational age at cerclage and cervical dilation were associated with adverse pregnancy outcomes (all P<0.05). Multivariate regression analysis indicated that only the levels of amniotic fluid WBC and TNF-α were independent risk factors for perinatal death. (3) Based on clinical practice, a multivariate logistic regression model was constructed including the levels of amniotic fluid TNF-α, WBC, gestational age at cervical cerclage, and cervical dilation. A nomogram and calibration curve were plotted, which suggested its good predictive value for adverse pregnancy outcomes. Conclusions:During the perioperative period of emergency cervical cerclage, the levels of amniotic fluid WBC, TNF-α, IL-1β, IL-2R, IL-6, IL-8, IL-10 are associated with adverse pregnancy outcomes, with amniotic fluid WBC and TNF-α showing the closest relationship. However, there is no significant correlation between maternal peripheral hemogram during the perioperative period and adverse pregnancy outcomes. A model constructed by amniotic fluid TNF-α, WBC, cervical cerclage gestational age, and cervical dilation has a good predictive effect on adverse pregnancy outcomes.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Background Exposure to ambient nitrogen dioxide (NO₂) could increase the risks of small for gestational age (SGA) and large for gestational age (LGA). Nevertheless, previous published studies usually use a time period over relatively long durations as the exposure window, such as trimester-specific or gestational months, to identify adverse pregnancy outcomes related susceptible exposure windows for ambient air pollution. At present, no study has explored associations of weekly-specific ambient air NO₂ exposure around pregnancy with SGA and LGA. Objective To evaluate the associations of exposure to ambient NO₂ over the preconception and entire pregnancy period with risks of SGA and LGA, as well as to explore critical windows of NO₂ exposure by refining exposure period to specific weeks. Methods Based on a birth cohort established by the project Environmental and LifEstyle FActors iN metabolic health throughout life-course Trajectories (ELEFANT) situated in Tianjin, 10 916 singleton pregnant women whose dates of the last menstrual period and delivery were both between June 2014 and June 2016, and whose gestational age were within 24-42 completed gestational weeks were included in this study. Each pregnant woman's exposures to ambient NO₂ throughout 12 weeks before pregnancy and pregnancy period were matched with daily average NO₂ concentrations obtained from the Chinese air quality reanalysis datasets (CAQRA). Distributed lag models incorporated in Cox proportional hazard regression models were applied to explore the associations of maternal exposure to weekly ambient NO₂ throughout 12 weeks before pregnancy and pregnancy period with risks of SGA and LGA after controlling for potential confounders including maternal age, ethnicity, educational level, occupation, body mass index before pregnancy, residence, times of gravidity and parity, smoking, alcohol consumption, husband smoking, and season of conception. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated per 3 μg·m⁻³ increase in ambient NO₂ concentrations. Results The average levels of maternal exposure to NO₂ over the preconception, first trimester, second trimester, third trimester, and entire pregnancy periods were (39.6±10.8), (42.7±10.5), (44.8±12.7), (37.7±11.1), and (41.6±4.8) μg·m⁻³, respectively. For a 3 μg·m⁻³ increase in NO₂ over the first trimester, the risk of SGA increased by 19.0% (95%CI: 8.0%-32.0%). For a 3 μg·m⁻³ increase in NO₂ over the preconception, first trimester, and entire pregnancy, the associated risks of LGA increased by 7.0% (95%CI: 1.0%-13.0%), 37.0% (95%CI: 29.0%-46.0%) and 19.0% (95%CI: 9.0%-31.0%), respectively. For SGA, the susceptible exposure windows for NO₂ were observed during the 7^th to 12^th preconceptional weeks and the 6^th to 12^th gestational weeks, with the strongest association found at the 12^th preconceptional week, when the risk of SGA increased by 6.0% (95%CI:3.2%-8.9%) for a 3 μg·m⁻³ increase in NO₂. For LGA, the susceptible exposure windows for NO₂ were observed during the 1^st to 12^th preconceptional weeks and the 1^st to 6^th gestational weeks, with the strongest association found at the 12^th preconceptional week, when the risk of LGA increased by 6.1% (95%CI: 4.5%-7.8%) for a 3 μg·m⁻³ increase in NO₂. Conclusion Exposure to ambient NO₂ is associated with increased risks of both SGA and LGA, and the most susceptible weekly exposure windows are nested within the 12 weeks before pregnancy and early pregnancy.

Objective:To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Methods:Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing , multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.Results:A heterozygous deletion variant, c. 4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. Thevariant was classified as pathogenic(PVS1 + PM2+ PM6)according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father’s TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA. Conclusion:The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients .

A 13-year-old male patient presented with skin abnormalities for more than 10 years and slow growth in body height for more than 5 years. Since the age of 6 months, erythema and scales had occurred on the extremities, and gradually spread to the trunk and face; brown pigmentation and punctate depigmentation appeared after subsidance of the erythema and scales, accompanied by dental caries, thickened palms and soles, nail thickening and peeling. Since the age of 6 years, the patient had presented with slow growth in body height, gonadal dysgenesis, sparse eyebrows and eyelashes, flat cheekbones and lameness in walking. In the past 10 years, neutrophil count had been found to be continuously lower than the normal reference value. Blood routine examination showed a neutrophil count of 1.1 × 10 9/L and a neutrophil proportion of 0.345; serum level of testosterone in the patient (< 0.087 nmol/L) was lower than normal levels. DNA was extracted from the peripheral blood of the patient and his parents, and gene mutation analysis was carried out by using whole-exome sequencing technology. Genetic testing showed compound heterozygous mutations in the USB1 gene of the patient, including the c.450-2A>G mutation inherited from his mother and the c.335de1G mutation inherited from his father, and the c.335de1G mutation had not been reported in China and other countries.

Objective:To evaluate the effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) on migraine.Methods:Database of PubMed, Embase, Cochrane, CNKI, Wangfang digital journals were searched for randomized controlled trials (RCTs) of CGRP-mAbs in treatment of migraine. Quality of enrolled literature was assessed by the software of Review Manager 5.3 and software of StataMP14 was employed to conduct meta analysis.Results:A total of 13 RCTs were included, including 6 218 adult migraine patients (experimental group: 2 679 patients, placebo group: 3 539 patients). Meta analysis suggested that CGRP-mAbs for preventive treatment of migraine significantly reduced the monthly migraine days from baseline (standardized mean difference (SMD)=-0.35, 95% CI-0.4--0.3) and monthly acute migraine-specific medication consumption from baseline (SMD=-0.38, 95% CI-0.43--0.32), as compared with placebo group. CGRP-mAbs for preventive treatment of migraine significantly increased the ≥50% reduction from baseline in migraine days per month ( RR=1.65, 95% CI 1.54-1.76). The adverse events were similar between the CGRP-mAbs group and placebo group ( RR=1.06, 95% CI 1.01-1.10). Conclusion:CGRP-mAbs are effective and safe for preventive treatment of migraine.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a kind of autoimmune disease aiming at NR1 subunit of NMDA receptor. In the early stage, functional damage is the main cause. Electroencephalogram (EEG) can reflect the abnormal brain function by recording the changes of EEG signals. The common EEG patterns of anti NMDA receptor encephalitis are slow wave abnormality, epileptic discharge, a large number of β activity, extreme delta brush, etc. Here we review the waveform characteristics, origin, pathogenesis and clinical value of EEG in patients with NMDA receptor encephalitis.
Anti-N-Methyl-D-Aspartate Receptor Encephalitis ; physiopathology ; Electroencephalography ; Humans ; Research ; trends