Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

Objective To understand the economic losses due to healthcare-associated infection(HAI)in patients after Da Vinci robotic thoracic surgery,and provide basis for preventing and controlling HAI after robotic surgery.Methods Patients who underwent Da Vinci robotic surgery from April 2019 to April 2023 were retrospective stu-died.Patients were divided into HAI group and non-HAI group based on the occurrence of postoperative infection.Through 1∶1 propensity score matching(PSM),31 cases were included in each group,economic losses of two groups of patients were compared.Results A total of 921 patients who underwent Da Vinci robotic thoracic surgery were included in the study,51 cases with HAI(HAI group)and 870 without HAI(non-HAI group).After 1∶1 PSM,31 cases were included in each group.Four covariates were compared between two groups of patients before PSM,namely gender,age,comorbidities,and the American Society of Anesthesiologists(ASA)grading,all with statistically significant differences(all P＜0.05).After PSM,distribution of the above covariates reached equilib-rium between the two groups(both P＞0.05).The median total expense for HAI group before PSM during hospi-talization was 88 711.72 Yuan,while 78 509.46 Yuan for the non-HAI group.The direct economic losses caused by HAI after Da Vinci robot surgery was 10 202.26 Yuan,mainly increased by expense of medicine,nursing,laborato-ry diagnosis,etc.Difference in western medicine expense was the highest(8 839.12 Yuan),out of which expense of antimicrobial agents accounted for the highest proportion(73.55％).Difference in daily hospitalization expense between HAI-group and non-HAI group was 502.38 Yuan.Length of hospital stay of patients in HAI group and non-HAI group were(21.59±10.62)and(13.92±9.21)days,respectively,with statistical differences(all P＜0.05).Conclusion The occurrence of HAI in patients undergoing Da Vinci robotic thoracic surgery leads to direct economic losses,with obvious increases in expenses of nursing,laboratory diagnosis,western medicine(mainly an-timicrobial agents).Length of hospital stay of patients also prolongs.

Objective To re-assess the Meta-analyses/network Meta-analyses on baloxavir marboxil in the treat-ment of influenza,and provide evidence-based reference for clinical use of baloxavir marboxil.Methods Meta-ana-lyses/network Meta-analyses on baloxavir marboxil in the treatment of influenza were retrieved from PubMed,Em-base,Cochrane Library,China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases,with re-trieval time from the inception of each database to December 11,2023.Literatures were screened according to the inclusion and exclusion criteria.Information of included literatures was extracted,and the methodological quality,reporting quality and evidence quality of the included literatures were assessed by assessment of multiple systematic reviews 2(AMSTAR-2)scale,preferred reporting items for systematic reviews and Meta-analyses(PRISMA)statement,as well as grading of recommendations,assessment,development,and evaluation(GRADE)system,respectively.Results A total of 7 Meta-analyses/network Meta-analyses were included.The results showed that in terms of alleviation time of influenza symptoms,the efficacy of baloxavir marboxil was not inferior to oseltamivir,peramivir,and zanamivir.In terms of the decrease in influenza virus titer 48 hours after medication,baloxavir mar-boxil was superior to oseltamivir and zanamivir.In terms of safety,baloxavir marboxil had a lower risk of drug-re-lated adverse events than oseltamivir,and was comparable to peramivir and zanamivir.The overall assessment result of methodological quality of AMSTAR-2 scale was relatively low,with 2 literatures being classified as low-level and 5 as extremely low-level.PRISMA scores ranged 15.5-22.The quality of overall report was moderate.Two lite-ratures were scored＞21,and the reports were relatively complete.There were 5 literatures with scores ranging 15-21,and the reports had certain deficiencies.The GRADE evidence quality grading results showed that among the in-cluded 199 outcome indicators,4 indicators were high-level evidence,49 were moderate-level evidence,118 indica-tors were low-level evidence,and 28 indicators were extremely low-level evidence.Conclusion Baloxavir marboxil is comparable to neuraminidase inhibitors in the alleviation time of influenza symptoms,superior to oseltamivir and zanamisvir in decreasing virus titer,and has a lower risk of adverse drug events(especially nausea)than oseltamivir.

AIM:To investigate the effects of semaglutide on inflammation and autophagy in hu-man AC16 cardiomyocytes under hypoxia/reoxy-genation conditions.METHODS:AC16 cells were randomly divided into four groups:control(CON),hypoxia/reoxygenation(H/R),hypoxia/reoxygen-ation+semaglutide(H/R+SEM),and hypoxia/reoxy-genation+semaglutide+3-MA(H/R+SEM+3-MA).All groups except CON underwent 8 hours of hypoxia followed by 12 hours of reoxygenation.Cell viabili-ty was measured by CCK-8.Levels of IL-1β and TNF-α were assessed by ELISA.Western blot analysis evaluated AMPK,p-AMPK,mTOR,p-mTOR,ULK1,p-ULK1,Beclin-1,and LC3.Autophagosomes were an-alyzed using laser confocal microscopy and trans-mission electron microscopy.The structure of au-tophagosome and autolysosome was observed by transmission electron microscopy.RESULTS:IL-1βand TNF-α levels increased significantly in the H/R group compared to CON(P＜0.01)but decreased in the H/R+SEM group(P＜0.01).In the H/R+SEM+3-MA group,inflammatory levels increased com-pared to the H/R+SEM(P＜0.05).Compared with the CON group,p-AMPK/AMPK and p-ULK1/ULK1 ratios increased significantly in the H/R group(P＜0.05,P＜0.01).The ratios further increased in the H/R+SEM group compared to H/R(P＜0.05,P＜0.01).But the two ratios decreased in the H/R+SEM+3-MA group compared to H/R+SEM(P＜0.01,P＜0.05).The pmTOR/mTOR had the opposite trend to the two previous ratios.The expression of Beclin1 and LC3 were significantly increased in group H/R com-pared to CON(P＜0.05),and which further in-creased in the H/R+SEM group compared to H/R(P＜0.01).But the two indicators decreased in the H/R+SEM+3-MA group compared to H/R+SEM(P＜0.01,P＜0.05).Laser confocal microscopy revealed increased autophagosome numbers in H/R group compared to CON(P＜0.05),and which further in-creased in the H/R+SEM group compared to H/R(P＜0.01).While the H/R+SEM+3-MA group showed a decrease compared to H/R+SEM(P＜0.05).CON-CLUSION:Semaglutide may moderate regulate au-tophagy through AMPK/mTOR/ULK1 pathway,re-duce the release of inflammatory factors,and alle-viate hypoxia/reoxygenation-induced inflammatory injury.

Objective To explore the effects and mechanisms of Sanzi Sijun Formula(SSF)in non-alcoholic fatty liver disease(NAFLD)through network pharmacology,molecular docking and molecular dynamics simulation;To carry out experimental validation in vivo and in vitro.Methods The active components and target genes of SSF were screened using TCMSP,TCMIP and TCMIO databases.NAFLD-related targets were screened using the GeneCards database,and the intersection targets were obtained to construct a protein-protein interaction network and screen for core targets.The intersection targets were imported into the DAVID database for GO and KEGG enrichment analysis.Molecular docking was performed using AutoDock Vina software between the key active components of SSF and core targets,and molecular dynamics simulations were conducted using Gromacs 2022 for 100 ns.C57BL/6J mice NAFLD model was established by diet induction.SSF was administered by gavage for 8 weeks.Liver histopathological changes and the levels of non-esterified fatty acids(NEFA)were detected.In vitro NAFLD model was established by inducing AML12 cells with palmitic acid(PA)for 24 hours.SSF-containing serum was added to incubate simultaneously.The lipid accumulation and cell viability were detected.The core targets of SSF intervention in the in vitro and in vivo NAFLD models were verified by RT-qPCR and Western blot.Results Network pharmacological analysis identified 75 active components in SSF and revealed 179 shared targets between these components and NAFLD.Ten main active components including arachidonate,12-senecioyl-2E,8E,10E-atractylodin,cerebrosterol,glycyrrhizol B and sinapic acid,etc.as well as 8 core targets were identified.GO enrichment analysis of targets mainly involved protein phosphorylation,inflammatory response,and apoptosis,while the KEGG enrichment analysis mainly included AGE-RAGE,TNF,AMPK,PPAR and NF-κB signaling pathways.Molecular docking demonstrated that the major active components of SSF exhibited favorable binding affinity and stability with the core targets.Molecular dynamics simulation confirmed the stability of the complex of glyasperin B with AKT1,SIRT1,STAT3,PPARG,and TNF.SSF alleviated the pathological damage of liver tissues in mice NAFLD model,reduced NAS score and NEFA levels in liver tissues(P<0.05).Additionally,SSF reversed lipid accumulation and decreased cell viability of PA-induced AML12 cells(P<0.01).Further in vivo and in vitro experiments demonstrated that SSF significantly reversed the elevated mRNA levels of TNF-α,IL-6,IL-1β and PPARγ and protein expression of STAT3(P<0.05,P<0.01)in NAFLD models,up-regulated the protein levels of SIRT1 and p-Akt/Akt(P<0.05,P<0.01).Conclusion SSF can improve NAFLD of both in vitro and in vivo models.The regulation of multiple targets,such as AKT,SIRT1,STAT3 and PPARG,by its multiple active components,and adjustment of multiple approaches,such as lipid metabolism disorder,inflammatory responses,are involved in the potential underlying mechanisms.

Objective:To evaluate the clinical value of three-dimensional(3D) printing-assisted fenestrated/branched endovascular aortic repair (F/B-TEVAR) for the treatment of endoleak after open surgery for type A aortic dissection.Methods:A multi-center retrospective case series analysis was conducted on 16 patients with anastomotic leakage following Stanford type A aortic dissection open repair, admitted to 12 medical centers between January 2019 and December 2023. All surgeries were led by the vascular surgery team from Department of Vascular Surgery, Nanjing Drum Tower Hospital. The study included 12 males and 4 females, with an age of (58.1±8.2) years (range: 42 to 75 years). Preoperative patient-specific 3D-printed models or 3D parametric surface topological guides were created based on aortic CT angiography data. These models assisted intraoperative external positioning of fenestration sites, combined with stent diameter selection and inner branch techniques to complete endovascular repair. Surgical procedures, complications, and clinical outcomes were evaluated, with follow-up CT imaging to assess efficacy.Results:All patients successfully underwent surgery without conversion to open repair. One patient had distal stent migration from a prior open repair, requiring intraoperative coverage of the main stent window and conversion to an in situ fenestration procedure. The mean operative time was (332.6±111.2)minutes (range: 80 to 460 minutes). No renal failure, paraplegia, or branch artery loss occurred. Postoperative follow-up ( M(IQR)) was 18(18) months(range: 6 to 36 months), with follow-up rates of 16/16 at 6 months, 10/16 at 12 months, 8/16 at 24 months, and 2/16 at 36 months. During follow-up, endoleak occurred in 3 patients, cerebral infarction in 1 patient, and death in 1 patient. The remaining patients demonstrated stable stent positioning, patent branches, and no endoleak. Conclusion:3D technology-guided F/B-TEVAR shows favorable mid-to short-term outcomes in treating anastomotic leakage after open repair of type A aortic dissection.

Objective:To explore the risk factors of acute Kemmochi type V anterior talofibular ligament (ATFL) injury in X-ray negative children and their predictive efficacy .Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 children with X-ray negative ATFL injury, who were treated at the outpatient department of Jinan Children′s Hospital from June 2023 to March 2025, including 55 boys and 37 girls, aged 5-14 years [8.8(7.0, 11.0)years]. The cause of injury was low-energy ankle sprain and X-ray examination showed no fracture, ie, X-ray negative. According to the Kemmochi classification for ATFL injury, the injury was classified as type V (Kemmochi type V group) in 42 patients and type I-IV (non-Kemmochi type V group) in 50. Gender, age, side of injury, time from injury to first visit, physical examination at the first visit [positive result of ankle inversion test, weight-bearing ability assessment, visual analogue score (VAS)], X-ray examination at the first visit (presence of os subfibulare), and musculoskeletal ultrasound examination at the first visit (swelling degree of ATFL, ankle joint effusion, enhanced blood flow signal of ATFL) were recorded in both groups. Univariate analysis and binary Logistic regression analysis were used to evaluate and determine the independent risk factors for X-ray negative Kemmochi type V ATFL injury in children. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive efficacy of each independent risk factor for Kemmochi type V ATFL injury. Results:Univariate analysis showed significant differences between the two groups in age, VAS, ATFL swelling degree, and ankle joint effusion ( P<0.05) but no significant differences in gender, side of injury, time from injury to the first visit, positive result of ankle inversion test, weight-bearing ability assessment, presence of os subfibulare or enhanced blood flow of ATFL ( P>0.05). Binary Logistic regression analysis indicated that age ( OR=0.79, 95% CI 0.65, 0.97, P<0.05) and ATFL swelling degree ( OR=6.97, 95% CI 1.38, 35.32, P<0.05) were significantly correlated with Kemmochi type V ATFL injury in X-ray negative children. ROC curve analysis showed that the AUC for age and ATFL swelling degree were 0.65(95% CI 0.54, 0.75) and 0.78(95% CI 0.68, 0.86) and the AUC for age combined with ATFL swelling degree was 0.83(95% CI 0.74, 0.90). The optimal threshold values of age and ATFL swelling degree were 9.3 years and 1.0 mm. Conclusions:Age and ATFL swelling degree are independent risk factors for Kemmochi type V ATFL injury in X-ray negative children. Both age and ATFL swelling degree have relatively high independent predictive efficacy, and the combined predictive efficacy of the two is even higher.

Objective:To explore the clinical efficacy of "four-step" aortic valve anatomic repair for bicuspid aortic valve(BAV) with aortic regurgitation(AR).Methods:From August 2021 to November 2024, a total of 298 consecutive patients with BAV-AR underwent aortic valve anatomic repair(AVr) in Shanghai Zhongshan Hospital Fudan University, 266 males and 32 females, with age of 39(29.5, 48.5) years. All patients underwent " four-step" three-dimensional anatomic repair of the aortic annulus and leaflets, 129(43.3%) patients via upper mini-sternotomy and 169(56.7%) patients via conventional median sternotomy, with the main steps including: (1) deep dissecting and annuloplasty of the virtual basal ring(VBR); (2) symmetrical repairing of leaflets; (3) replacement or remodeling of the sinus of Valsalva; (4) annuloplasty of the sinotubular junction(STJ). Basal and perioperative data were retrospectively collected, and statistical analysis was performed in conjunction with follow-up data.Results:All patients successfully underwent anatomical repair without transferring to valve replacement during operation. Among them, 43 patients underwent aortic root reimplantation technique(Reimplantation group), while 255 patients underwent modified aortic root sleeve remodeling technique(Sleeve group). The median cardiopulmonary bypass time for the Reimplantation and Sleeve groups were 154(134, 169) minutes and 111(95, 129) minutes, respectively( P<0.05); the median aortic cross-clamp time were 112(100, 131) minutes and 80(67, 94) minutes, respectively( P<0.05). Preoperative TEE showed 35 patients(81.4%) and 229 patients(89.8%) with moderate and severe AR in Reimplantation and Sleeve groups, respectively. Postoperative TEE showed 41 patients(95.3%) with no/trace AR and 2 patients(4.7%) with central mild AR in Reimplantation group, while 212 patients(83.1%) with no/trace AR and 43 patients(16.9%) with central mild AR in Sleeve group. Follow-up was completed in all patients, with a median follow-up of 12.9(4.7, 21.2) months. Echocardiography was obtained in 271 patients(90.9%) at the latest follow-up, including no/trace AR in 167 patients(56.0%), mild AR in 89 patients(29.9%), moderate AR in 14 patients(4.7%), and severe AR in 1 patient(0.3%). Conclusion:Aortic valve anatomic repair by standardized "four-step" approach is safe and reproducible. Satisfied short- and mid-term outcome have obtained in selected BAV-AR patients.

Objective:To investigate the clinical manifestations, gene mutation characteristics, imaging and video electroencephalogram (VEEG) characteristics of patients with dentatorubral-pallidoluysian atrophy (DRPLA).Methods:The clinical data of 9 patients with genetically diagnosed DRPLA in the Neurology Center, Beijing Tiantan Hospital, Capital Medical University from January 2018 to January 2023 were collected, and the clinical data of DRPLA patients reported in China were retrieved and summarized.Results:A total of 45 cases were included. The clinical characteristics were summarized as follows: (1) The male to female ratio of 45 patients was 1.00∶1.25, and the age of onset was (28.11±14.58) years. (2) The main clinical symptoms of juvenile type, early-onset adult type and late-onset adult type were analyzed, and the results showed that the frequency of seizures in juvenile type (16/17) was higher than that in early-onset adult type (8/21) and late-onset adult type (2/7), with statistically significant difference (χ 2=15.971, P<0.001). In addition, the frequency of cognitive impairment in juvenile type (16/17) was also higher than that in early-onset adult type (15/21) and late-onset adult type (2/7), also with statistically significant difference (χ 2=10.177, P=0.005). Cognitive impairment, language disorder and involuntary movement were common in early-onset adult patients, and about half of the patients had ataxia. Ataxia and language disorder were more common in late-onset adult patients, while seizures and cognitive impairment were rare. (3) In imaging, cerebellum and brainstem atrophy was the most common, followed by cortical atrophy and white matter lesions. (4) The number of trinucleotide (CAG) repeats was 53-79, and there was a significant negative correlation between the number of CAG repeats and the age of onset ( r=-0.765, P<0.001), that means the younger the age of onset, the higher the number of CAG repeats. (5) In terms of electrophysiology, 21 patients provided complete VEEG data, of which slowed activity (52%, 11/21) and generalized discharge (71%, 15/21) were more common, and focal discharge (33%, 7/21) was uncommon. Conclusions:DRPLA patients can present with epilepsy, cerebellar ataxia, and other clinical manifestations. Brainstem and cerebellar atrophy and white matter lesions can be relatively characteristic in imaging. In terms of electrophysiology, slowed activity and generalized discharge are more common. DRPLA patients are easy to be misdiagnosed in clinical practice and genetic confirmation helps confirm the diagnosis.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.