This study investigates the neuroprotective potential of extracellular vesicles (EVs) delivering quercetin-3-O-β-d-glucuronic acid (QG-EVs) in cerebral ischemia-reperfusion injury (CIRI). Targeted brain delivery of QG-EVs was confirmed, with neuron cells identified as pivotal in modulating CIRI through single-cell RNA sequencing (scRNA-seq). Activating transcription factor 4 (Atf4) was highlighted as a critical regulatory factor, and in vitro studies revealed that silencing Atf4 diminished the neuroprotective effects of QG-EVs, increasing oxidative stress levels and neuronal apoptosis. In a CIRI mouse model, the knockdown of Atf4 attenuated the protective outcomes provided by QG-EVs, further affirming the role of Atf4 in mediating neuroprotection. Behavioral assessments and protein analysis showed that QG-EVs significantly reduced neuronal damage and pro-apoptotic markers, while improving neurological function via Atf4 upregulation. The outcomes hint at the potential of QG-EVs as a beneficial therapeutic modality to mitigate neuronal damage in CIRI by enhancing Atf4 expression, highlighting its potential for improving ischemic stroke outcomes.

Objective To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation(AF),and to evaluate the predictive value of SNORD55 for prognosis.Methods A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study.Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected.Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients.The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients.The area under the receiver operating characteristic curve(AUC)was utilized to evaluate the discrimination,and the net reclassification index(NRI)and comprehensive discriminant improvement index(IDI)were calculated to evaluate the improvement of reclassification ability.Decision curve analysis(DCA)was applied to analyze the change in clinical net benefit.Results The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients.In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value[0.80(95％CI:0.67～0.93)vs 0.67(95％CI:0.53～0.81),P＜0.05].In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI[54.3(95％CI:10.6～61.9)vs 31.9(95％CI:2.8～47.5),P＜0.05]and IDI[16.1(95％CI:2.4～27.0)vs 7.9(95％CI:0.5～14.8),P＜0.05].The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.Conclusion Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.

Objectives To explore the association of peripheral blood PIWI-interacting RNA,piR-hsa-2700592,with all-cause mortality and stroke outcomes in patients with atrial fibrillation(AF),and to determine whether piR-hsa-2700592 has the potential to be an AF biomarker.Methods A total of 127 patients with non-valvular AF were enrolled,and the relative expression level of plasma piR-hsa-2700592 was detected.Cox proportional hazard regression was used to analyze the correlation between the expression of piR-hsa-2700592 and all-cause death as well as stroke outcome in the patients.Then the molecule expression level was combined with CHA2DS2-VASc score and ABC stroke(or death)score to establish 2 new prediction models,the improvement of the predictive performance was compared and analyzed.Receiver operating characteristic(ROC)curve analysis(area under the curve,AUC),net reclassification index(NRI),and comprehensive discriminant improvement index(IDI)were used to evaluate the predictive performance,and decision curve analysis(DCA)was employed to assess the clinical benefit.Results Multivariate Cox regression analysis showed that the patients with higher expression level of piR-hsa-2700592 in peripheral blood had a higher risk of stroke(HR:2.203,95%CI:1.120～4.332;P=0.022).In the stroke outcome,combination of plasma piR-hsa-2700592 expression level with CHA2DS2-VASc score and ABC stroke score obtained an AUC of 0.70(95%CI:0.55～0.85,P＜0.001)and 0.84(95%CI:0.73～0.96,P=0.02),respectively.But,no significant association was observed between high plasma piR-hsa-2700592 level and all-cause mortality in the AF patients(HR:1.997;95%CI:0.884～4.509;P=0.096).Combination of plasma piR-hsa-2700592 level improved the discriminative capability than the single CHA2DS2-VASc score and ABC stroke score models,with an NRI and IDI value of 44.20%(95%CI:3.40～59.90,P＜0.001)and 8.20%(95%CI:0.60～15.40,P＜0.001),respectively for the new CHA2DS2-VASc score model,and an NRI and IDI value of 44.20%(95%CI:9.80～58.90,P＜0.001)and 10.40%(95%CI:0.70～21.40,P＜0.001),respectively for the new ABC stroke score model.The DCA curve showed that both new prediction models obtained better net clinical benefits.Conclusion High peripheral blood expression of piR-hsa-2700592 is an independent risk factor for stroke in the AF patients,and the indicator has a good predictive value for prognosis of the patients.piR-hsa-2700592 might be used as a potential biomarker in the diagnosis and prevention of cardiovascular diseases.

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,with a global prevalence of approximately 30.05% to 32.4% .It is closely associated with various other diseases.In recent years,microRNAs(miRNAs)have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD.miRNAs play significant roles in both lipid metabolism and insulin resistance,exerting specific regulatory functions in the development and progression of NAFLD.miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes.This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism,insulin resistance,and the occurrence and development of NAFLD.

Objective:To research the efficacy and safety of robotic thyroidectomy and bilateral modified radical neck dissection through bilateral axillo-breast approach (BABA) .Methods:We retrospectively analyzed the clinical data of 37 patients with thyroid cancer who received bilateral modified radical neck dissection through the BABA at the Department of Thyroid and Breast Surgery of the 960th Hospital of the People’s Liberation Army from Jan. 2014 to Jan. 2023. There were 24 females and 13 males, and the average age of the patients was (33,22±10.53) years old. The tumor diameter, number of lymph node dissection and metastasis in the central and lateral regions, average operation time, average hospital stay, complications, and aesthetic score were recorded. SPSS 25.0 software was used for statistical analysis, and the measurement data was calculated using mean ± standard deviation ( ± s), and the counting data was expressed in percentages and numbers. Results:A total of 37 thyroid cancer patients underwent robotic bilateral regional lymph node dissection. The 37 patients received total thyroidectomy, bilateral central compartment and cervical lateral regional lymph node dissection. All the pathological types were papillary carcinoma, with a maximal tumor diameter of (1.47±0.85) cm. The average number of central lymph nodes dissected was 19.46±8.84, and there were (10.24±5.95) metastases; The average number of lymph nodes removed from the bilateral cervical region was 38.92±14.21, and there were (7.92±5.84) metastases. The average operation time was (288.05±77.09) min, the average length of stay in the hospital was (10.76±3.92) days, and the average length of stay in the hospital following surgery was (8.03±2.08) days. These patients had no permanent hypoparathyroidism, permanent recurrent laryngeal nerve palsy, infection, accessory nerve injury and phrenic nerve injury after operation. Transient hypoparathyroidism occurred in 15 patients, transient recurrent laryngeal nerve palsy occurred in 1 patient, and chyle leak occurred in 2 patients. One month after surgery, the aesthetic score was 9.51±0.69.Two patients were found lymph node metastases during the (27.81±15.10) months of follow-up, and received robotic cervical lymph node dissection with BABA.Conclusion:For carefully chosen thyroid cancer patients with bilateral lateral cervical region lymph node metastases, robotic bilateral cervical lymph node regional dissection via BABA is safe and feasible, and good cosmetic results can be obtained.

Refractory angina is characterized by recurrent and persistent angina with a duration of not less than three months， which is related to reversible ischemia and hypoxia caused by coronary stenosis and obstruction. It mainly involves obstructive coronary artery disease and non-obstructive coronary artery disease with coronary artery spasm and coronary microvascular dysfunction. “Stasis and toxin” play an important role in the pathogenesis of cardiovascular diseases. The pathogenesis of stasis and toxin is stubborn filthy turbidity featured by slow accumulation and sudden onset，and rapid changes，which coincides with the characteristics of refractory angina which is complex and changeable，prolonged and difficult to cure. The pathogenesis of refractory angina involves a combination of underlying deficiency and excessive manifestation， with "stasis and toxin" playing a crucial role as an important pathological factor in the whole process of refractory angina. Traditional Chinese medicine （TCM） employs a holistic approach known as "activating blood circulation and removing toxins"， which is supplemented by various methods to tonify Qi and warm Yang， nourish the kidneys and invigorate the spleen， clear heat and transform phlegm. This approach applies anti-inflammatory measures， regulates lipid metabolism， inhibits oxidative stress and thrombus formation， protects endothelial function in blood vessels， as well as establishes collateral circulation for the prevention and treatment of refractory angina. Therefore，based on the theory of "stasis and toxin"，combined with TCM theory and modern medical research，this paper discusses the pathogenesis of refractory angina and the prevention and treatment strategy of TCM，and elucidates the reasons for the difficulty in curing refractory angina and the relationship between refractory angina and common angina pectoris，coronary microvascular dysfunction，coronary artery spasm and obstructive coronary artery disease，hoping to provide certain theoretical basis and clinical ideas for the prevention and treatment of refractory angina with TCM.

Objective To investigate the current situation of competency and professional activities of pediatric rehabilitation thera-pists in Jiangsu,Shanghai and Zhejiang. Methods A questionnaire survey was conducted on 168 pediatric rehabilitation therapists in Jiangsu,Shanghai and Zheji-ang,from December,2022 to February,2023,and the general information and the competency were obtained.A total of 35 pediatric rehabilitation therapists were interviewed one-on-one,from October,2022 to January,2023,using thematic framework. Results A total of 162 effective questionnaires were collected.The level of competency of pediatric rehabilitation thera-pists was(3.44±0.87);and it was higher in professional literacy(3.90±0.77)and practice(3.83±0.77),and lower in management and leadership(2.92±1.44),and research(2.14±1.64).Latent class analysis showed that the thera-pists could be divided into four categories,of which the"medium competency"accounted for the most proportion(34.57%),and"low learning and research"was the least(8.64%).The interviews identified problems of compe-tency such as maintaining communication with children's families and managing self-professional development. Conclusion Self-reported rehabilitation competency levels of pediatric rehabilitation therapists in three provinces and cit-ies are above three points in all four dimensions,except for the management and leadership dimension,where the score is below three points.

Objective To investigate the application of susceptibility weighted imaging(SWI)and diffusion tensor imaging(DTI)parameters in clinical diagnosis and prognosis evaluation of mild traumatic brain injury(mTBI).Methods Forty-four mTBI patients were enrolled for observation group,and 32 healthy volunteers were selected as controls.All the patients underwent conventional magnetic resonance imaging(MRI),SWI and DTI scanning of the brain.Fractional anisotropy(FA)and apparent diffusion coefficient(ADC)were measured in regions of interest(frontal lobe,genu of corpus callosum,external capsule,internal capsule,thalamus,splenium of corpus callosum,and semioval center).The Glasgow outcome Scale-Extended for traumatic brain injury(GOSE)-TBI was used to evaluate the prognosis at 6 months after discharge.FA and ADC values were compared between two groups by t-test.Correlations between imaging parameters and prognosis were analyzed by Spearman test.Results SWI showed microhemorrhages in 88.6%mTBI patients,with a mean number of 2.36±1.26(range 0-5)and a mean area of(349.48±225.82)mm2.The mean GOSE-TBI score was 7.50±0.51(range 7-8)in the observation group at 6 months after discharge,with 50.00%(22/44)of the patients scored 8.The hemorrhage area was negatively correlated with the GOSE-TBI score(P<0.001).The FA values of the frontal lobe,genu of corpus callosum and left internal capsule in the observation group were significantly lower than those in the control group(P<0.05).There was no significant difference in the FA value of the thalamus between the two groups(P>0.05).The FA values of the frontal lobe and genu of corpus callosum were positively correlated with the GOSE-TBI score(P<0.001).The FA values of the internal capsule and corpus callosum splenium were negatively correlated with the GOSE-TBI score(P<0.05).There was no significant difference in the ADC values between the two groups(P>0.05).Conclusion SWI can sensitively detect microbleeds in mTBI patients.DTI shows mild white matter injury in mTBI patients.FA value is related to the GOSE-TBI score,and is a sensitive index for evaluating the severity and prognosis of mTBI.

Atherosclerosis is a vascular disease characterized by arterial occlusion formed by the pathological accumulation of pathological vascular cells and apoptotic cell debris. Atherosclerotic vulnerable plaque is an important pathological basis for inducing severe thrombotic cardiovascular events， and the study of its etiology and pathogenesis has always been a hot issue in the field of cardiovascular research. Efferocytosis is a new type of programmed death cell removal， which refers to the process of macrophages phagocytosing and degrading apoptotic cells to prevent secondary necrosis. It is a key homeostatic mechanism in the body's physiological process. In the pathological state， the dysfunction of efferocytosis causes the pathological accumulation of apoptotic cells and necrotic debris， leading to the occurrence of secondary cell necrosis and the continuous release of intracellular toxic content and inducing inflammatory regression disorders and cholesterol metabolism disorders， which are closely related to the occurrence and development of atherosclerotic vulnerable plaques. The theory of ''blood stasis and toxin'' is an important theory of traditional Chinese medicine （TCM） to explain the occurrence and development of atherosclerosis. Atherosclerosis starts from the pathological state of blood stagnation. Prolonged blood stagnation leads to blood stasis and toxic substances. Blood stasis and toxic pathogens interact with each other in blood vessels and eventually form plaques in blood vessels. The theory of ''blood stasis and toxin causing a catastrophe'' is an important understanding of the occurrence and development of acute cardiovascular events. From the perspective of TCM theory， the pathophysiological mechanism of efferocytosis is similar to the etiology and pathogenesis of the ''blood stasis and toxin'' in TCM. Therefore， this paper took the theory of ''blood stasis and toxin'' as the breakthrough point to explore the mechanism of efferocytosis in atherosclerotic vulnerable plaques， and proposed a detoxification and blood circulation method to regulate cell burial to prevent and treat atherosclerotic vulnerable plaques. The research strategy aims to provide new ideas and theoretical basis for the prevention and treatment of atherosclerosis by detoxification and blood circulation.

Objective:To investigate the influences of SCN3A gene polymorphism(c.905A>G/p.N302S and c. 1441C>T/p.L481L) on the efficacy of valproic acid sodium in the treatment of Zhuangzu epilepsies.Methods:Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)technique and the way of direct sequence, the SCN3A gene c. 905A>G/p.N302S and c. 1441C>T/p.L481L genotypes in peripheral blood were detected in 244 epileptic patients (85 cases in effective group and 139 cases of ineffective group) in the standardized treatment of valproic acid sodium.The blood concentration of valproic acid sodium was detected by LC-MS.Evaluating the correlation between the genotype and alleles of two groups of patients and the efficacy of valproic acid sodium and analyzing the difference of valproic acid sodium's blood concentration between different genotypes.The linkage disequilibrium of c. 905A>G/p.N302S and c. 1441C>T/p.L481L were analyzed by software SHEsis.Results:The allele and genotype distribution in c. 905A>G/p.N302S loci between effective group(A, G allele: 50.6%, 49.4%, AA, AG, GG genotype: 27.1%, 47.1%, 25.8%) and ineffective group(A, G allele: 37.4%, 62.6%, AA, AG, GG genotype: 16.6%, 41.7%, 41.7%) had statistically significant difference(χ 2=7.501, P=0.006; χ 2=7.907, P=0.019). There was no significant difference in allele and genotype distribution of c. 1441C>T/p.L481L loci between effective group(C, T allele: 47.1%, 52.9%, CC, CT, TT genotype: 23.5%, 47.1%, 29.4%) and ineffective group(C, T allele: 38.8%, 61.2%, CC, CT, TT genotype: 18.7%, 40.3%, 41.0%)(χ 2=2.920, P=0.088; χ 2=3.099, P=0.212). Compared with the AA + AG genotype, the GG genotype at c. 905A>G/p.N302S locus significantly reduced the efficacy of valproic acid sodium ( OR=2.051, 95% CI=1.136-3.703). Compared with genotypes AA+ AG, there were no significant differences in blood concentration of genotype GG of c. 905A>G/p.N302S ( t=3.256, P=0.137). Compared with genotypes CC+ CT, there were no significant differences in blood concentration of genotype TT of c. 1441C>T/p.L481L( t=4.628, P=0.082). c.905A>G/p.N302S and c. 1441C>T/p.L481L were without linkage disequilibrium. Conclusion:These results suggest that the single nucleotide polymorphisms of c. 905A>G/p.N302S in SCN3A genes may play a role in the resistivity of valproic acid sodium in Zhuangzu epilepsies.