ObjectivePeripheral nerve injury is a common clinical condition that can impair the regulatory function of target organs, leading to functional disability; severe injuries may even result in lifelong disability. Therefore, how to effectively promote the morphological and functional reconstruction of injured peripheral nerves has become a critical scientific issue that urgently needs to be addressed. This study biomimicked the highly oriented structure and electrophysiological properties of peripheral nerves and investigated the feasibility and effectiveness of combining electrical stimulation (ES) with oriented conductive substrates for the repair of injured peripheral nerves at the cellular level. MethodsPolydimethylsiloxane (PDMS) substrates with oriented microgroove structures of varying widths (0, 5, 10, and 20 μm) were fabricated using silicon wafers with micropatterned grooves as templates. Graphene-based conductive patterned substrates (GCPSs) with oriented microgrooves were then constructed via soft lithography and designated as GCPS 0, GCPS 5, GCPS 10, and GCPS 20 according to the groove width. The GCPSs were prepared from collagen/polycaprolactone (PCL) matrices containing 1.0 wt% graphene, and their morphology, wettability, and conductivity were characterized. Mesenchymal stem cells (MSCs) viability, proliferation, adhesion, and orientation on the substrates were evaluated before ES treatment. Then, ES at a frequency of 2 Hz and field strengths of 10, 20, or 50 mV/cm were applied to the cells for 10 min daily, over 3 or 7 consecutive days. Neural differentiation was assessed by morphological observation, immunofluorescence staining, and analysis of neural lineage-related markers. ResultsThe oriented microgroove PDMS substrates supported long-term MSCs growth, guided cells to align along the groove direction, and promoted a morphological transition toward neural-like cells, exhibiting the capacity to induce MSCs differentiation toward the neural lineage. Microgroove structures effectively guided the alignment of MSCs and promoted the development of a more elongated, neural-like morphology, with the most pronounced morphological changes observed on grooves of 10 and 20 μm in width. Meanwhile, the incorporation of graphene endowed the GCPSs with favorable electrical conductivity, though the groove width did not significantly affect the conductive performance. The GCPSs showed good cytocompatibility with MSCs, and cell proliferation on these substrates exhibited a time-dependent pattern, with no significant effect observed from groove width. The inductive effect of ES combined with GCPSs on MSCs differentiation toward specific neural lineages was co-regulated by ES intensity (0, 10, 20, and 50 mV/cm) and microgroove width. ES at 10 mV/cm and 20 mV/cm promotes MSCs differentiation toward neurons on microgrooved substrates of various widths (5, 10, and 20 μm); under the same ES intensities, microgrooves with widths of 5 μm and 10 μm are more favorable for MSCs differentiation toward glial cells/SCs. Notably, low-intensity ES (10 or 20 mV/cm) combined with GCPS 10 significantly enhanced the neural differentiation of MSCs. Neurotrophic factor secretion levels by MSCs cultured on various GCPS substrates after 3 d of ES application was further detected. There were no significant differences in nerve growth factor‑β (NGF‑β) and brain-derived neurotrophic factor (BDNF) concentrations among the GCPS 5, GCPS 10, and GCPS 20 substrates, and these levels were not affected by variations in ES intensity. Under ES at 10 mV/cm, the glial cell line-derived neurotrophic factor (GDNF) concentration in each GCPS substrate was higher than that in the corresponding non-ES group on the same substrate. However, as ES intensity increased, the GDNF concentration decreased to varying degrees. ConclusionThis study demonstrates that the combined strategy of “oriented topographical structure+ES” can effectively promote the neural differentiation of MSCs and holds promise for accelerating the repair process of peripheral nerve injuries.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective To investigate the classification capability of a deep learning classification model based on biparametric mag-netic resonance imaging(bpMRI)for clinically significant prostate cancer(csPCa)and clinically insignificant prostate cancer(cisPCa).Methods A retrospective analysis was conducted on the data of 565 prostate bpMRI patients.A deep learning classification model was established for csPCa.The patients were randomly divided into training set(452 cases)and internal test set(113 cases)at a ratio of 8︰2.Internal validation was performed,followed by external validation(external validation set)using data from 120 patients across four different hospitals.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve,F1 score,precision,sensi-tivity,specificity,accuracy,and calibration curves were used to evaluate the model.Decision curve analysis(DCA)was also applied to assess the clinical benefit of the model.Results The deep learn-ing classification model for csPCa classification demonstrated the following performance across the training set,internaltest set,and external validation set:sensitivity of 0.986,0.887,and 0.750;specificity of 0.967,0.850,and 0.976;precision of 0.963,0.839,and 0.818;accuracy of 0.974,0.862,and 0.792;F1 score of 0.974,0.862,and 0.783;and AUC of 0.998,0.896,and 0.883,respec-tively.The calibration curves for all three datasets showed high consistency between predicted and actual probabilities.DCA indicated that the highest net benefit threshold probabilities for the training set,internal test set,and external validation set were 0.2-0.7,0.2-0.6,and 0.2-0.5,respectively.Conclusion The deep learning classification model demonstrated excellent performance in classifying csPCa and exhibited good generalizability,which is worhty of clinical application.

Objective To investigate the classification capability of a deep learning classification model based on biparametric mag-netic resonance imaging(bpMRI)for clinically significant prostate cancer(csPCa)and clinically insignificant prostate cancer(cisPCa).Methods A retrospective analysis was conducted on the data of 565 prostate bpMRI patients.A deep learning classification model was established for csPCa.The patients were randomly divided into training set(452 cases)and internal test set(113 cases)at a ratio of 8︰2.Internal validation was performed,followed by external validation(external validation set)using data from 120 patients across four different hospitals.The area under the curve(AUC)of the receiver operating characteristic(ROC)curve,F1 score,precision,sensi-tivity,specificity,accuracy,and calibration curves were used to evaluate the model.Decision curve analysis(DCA)was also applied to assess the clinical benefit of the model.Results The deep learn-ing classification model for csPCa classification demonstrated the following performance across the training set,internaltest set,and external validation set:sensitivity of 0.986,0.887,and 0.750;specificity of 0.967,0.850,and 0.976;precision of 0.963,0.839,and 0.818;accuracy of 0.974,0.862,and 0.792;F1 score of 0.974,0.862,and 0.783;and AUC of 0.998,0.896,and 0.883,respec-tively.The calibration curves for all three datasets showed high consistency between predicted and actual probabilities.DCA indicated that the highest net benefit threshold probabilities for the training set,internal test set,and external validation set were 0.2-0.7,0.2-0.6,and 0.2-0.5,respectively.Conclusion The deep learning classification model demonstrated excellent performance in classifying csPCa and exhibited good generalizability,which is worhty of clinical application.

Objective To explore the risk factors for recurrence after unilateral biportal endoscopy in patients with lumbar disc herniation.Methods Clinical data of 156 patients with lumbar disc herniation were retrospectively analyzed.All the patients underwent unilateral biportal endoscopy treatment.Follow up for 2 years after surgery,and the recurrence rate of all patients was recorded.The clinical characteristics of patients in the recurrent and non recurrent groups were compared,the factors influencing postoperative recurrence were analyzed by multivariate Logistic regression.Results After a 2-year follow-up,a total of 22 patients experienced recurrence,with a recurrence rate of 14.10%(22/156).The results of multivariate Logistic analysis showed that,the age>60 years old,fiber ring break>5 mm,incomplete nucleus pulposus removal,and postoperative intervertebral motion>10 ° were independent risk factors for recurrence after unilateral biportal endoscopy in patients with lumbar disc herniation(P<0.05).Conclusion Age>60 years old,fiber ring break>5 mm,incomplete removal of the nucleus pulposus,and postoperative intervertebral motion>10 ° were independent risk factors for recurrence after unilateral biportal endoscopy in patients with lumbar disc herniation,and prevention should be strengthened.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae. Guanxinning Tablet (GXNT), which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong, has significant antithrombotic activity, but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear. In this paper, the main active components, potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro, network pharmacology analysis, molecular docking technology and molecular biology experiments. The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner. Using network pharmacology analysis, it was revealed that salvianolic acid B, tanshinone IIA, caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein (HMGB1), tumor necrosis factor (TNF), interleukin 6 (IL6) and AKT serine/threonine kinase 1 (AKT1). HMGB1 signaling pathway is one of its key common mechanisms. Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets. In summary, this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae. The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2023187g1549).

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

Objective To explore the safety and efficacy of radiofrequency catheter ablation(RCFA)in patients with persistent atrial fibrillation(AF)/atrial flutter(AFL)and heart failure(HF)with left ventricular ejection fraction≤35％.Methods This study is a retrospective study.Patients with persistent AF/AFL and HF with left ventricular ejection fraction≤ 35％admitted to Beijing Anzhen Hospital from January 2018 to March 2024 were enrolled.The perioperative characteristics and complications changes in echocardiographic parameters,and follow-up outcomes were analyzed.Results A total of 45 patients were enrolled with a mean age of(56±13)years and a mean LVEF of(28±4)％.The ablation strategy was circumferential pulmonary vein isolation and empirical linear ablation.The operation time and fluoroscopy time were 120(120,163)min and 5(4,10)min respectively.The patients mainly underwent linear ablation including circumferential pulmonary vein isolation(38,84.4％),cavotricuspid isthmus(37,82.2％),roofline(34,75.6％),mitral isthmus(34,75.6％).21(46.7％)patients underwent ehtanol infusion into the vein of Marshall.24(53.3％)patients underwent electrocardioversion.All patients restored sinus rhythm immediately after RFCA and had no perioperative complications.After a median follow-up of 22.9(7.8,31.0)months,2 patients died of cardiovascular disease,1 patient underwent heart transplantation,14(33.3％)patients were readmitted for cardiovascular disease,and 10 patients(23.8％)had recurrence of AF.The mean LVEF of the 28 patients who obtained LVEF at the last follow-up increased from(28±4)％to(51±14)％,and the average improvement of LVEF was(23±13)％(P＜0.0001).15 of these patients had complete recovery of left ventricular systolic function(LVEF≥ 50％).Conclusions RFCA is safe and effective for patients with persistent AF/AFL and HF with LVEF ≤ 35％,and can improve patient's cardiac function and significantly increase LVEF.

Objective To explore the safety and efficacy of radiofrequency catheter ablation(RCFA)in patients with persistent atrial fibrillation(AF)/atrial flutter(AFL)and heart failure(HF)with left ventricular ejection fraction≤35％.Methods This study is a retrospective study.Patients with persistent AF/AFL and HF with left ventricular ejection fraction≤ 35％admitted to Beijing Anzhen Hospital from January 2018 to March 2024 were enrolled.The perioperative characteristics and complications changes in echocardiographic parameters,and follow-up outcomes were analyzed.Results A total of 45 patients were enrolled with a mean age of(56±13)years and a mean LVEF of(28±4)％.The ablation strategy was circumferential pulmonary vein isolation and empirical linear ablation.The operation time and fluoroscopy time were 120(120,163)min and 5(4,10)min respectively.The patients mainly underwent linear ablation including circumferential pulmonary vein isolation(38,84.4％),cavotricuspid isthmus(37,82.2％),roofline(34,75.6％),mitral isthmus(34,75.6％).21(46.7％)patients underwent ehtanol infusion into the vein of Marshall.24(53.3％)patients underwent electrocardioversion.All patients restored sinus rhythm immediately after RFCA and had no perioperative complications.After a median follow-up of 22.9(7.8,31.0)months,2 patients died of cardiovascular disease,1 patient underwent heart transplantation,14(33.3％)patients were readmitted for cardiovascular disease,and 10 patients(23.8％)had recurrence of AF.The mean LVEF of the 28 patients who obtained LVEF at the last follow-up increased from(28±4)％to(51±14)％,and the average improvement of LVEF was(23±13)％(P＜0.0001).15 of these patients had complete recovery of left ventricular systolic function(LVEF≥ 50％).Conclusions RFCA is safe and effective for patients with persistent AF/AFL and HF with LVEF ≤ 35％,and can improve patient's cardiac function and significantly increase LVEF.