Patients with Takayasu arteritis combined with aortic valve disease often have a poor prognosis following surgical valve replacement, frequently encountering complications such as perivalvular leakage, valve detachment, and anastomotic aneurysm. This article presents a high-risk case wherein severe aortic valve insufficiency associated with Takayasu arteritis was successfully managed through transcatheter aortic valve implantation via the transapical approach. The patient had satisfactory valve function with no complications observed during the six-month postoperative follow-up. This case provides a minimally invasive and feasible alternative for the clinical management of such high-risk patients.

Objective To explore the anesthesia management experience in the interventional treatment of pediatric congenital heart diseases (CHD) percutaneously guided by transthoracic echocardiography (TTE) on a mobile operating platform. Methods From March to July 2023, a total of 13 patients from remote areas underwent interventional treatment for CHD on the mobile operating platform of Fuwai Yunnan Cardiovascular Hospital. Patients who received non-tracheal intubation general anesthesia were retrospectively included. Results Eight children who had difficulty cooperating with the surgery (due to young age, emotional tension, crying) received monitored anesthesia care with local anesthesia supplemented by sedative and analgesic drugs while maintaining spontaneous breathing under the monitoring and management of an anesthesiologist (i.e., non-tracheal intubation general anesthesia). Among them, there were 5 males and 3 females, with an age of (6.95±3.29) years and a body weight of (19.50±6.04) kg. Through transthoracic echocardiography, they were diagnosed with atrial septal defect (6 patients), residual shunt after patent ductus arteriosus ligation (1 patient), and severe pulmonary valve stenosis (1 patient). The surgery proceeded smoothly, with satisfactory anesthesia and surgical effects, complete analgesia, and satisfactory postoperative recovery. There was 1 patient of body movement and 1 patient of respiratory depression during the operation, and both patients completed the surgery successfully after treatment. All children had no serious surgery- and anesthesia-related complications. The anesthesia time was 40.5 (34.5, 47.5) min, the surgery time was 39.0 (33.0, 45.5) min, and the recovery time was 43.0 (28.0, 52.5) min Conclusion Interventional surgery for CHD guided by TTE at a mobile platform is a minimally invasive approach without radiation damage. Non-tracheal intubation general anesthesia with spontaneous breathing can be safely and effectively implemented in children who cannot cooperate.

Objective:To preliminarily assess the biocompatibility and durability of the TruDelta TM transcatheter mitral valve replacement (TMVR) system. Method:Six adult sheep were divided into 3 groups based on the duration of follow-up: 30 days ( n=1), 90 days ( n=3) and 180 days ( n=2). The TruDelta TM TMVR system was implanted through a transapical approach under transesophageal echocardiographic guidance. The operability of the TMVR system was evaluated using an instrument performance evaluation scale (consisting of 39 items), with scores ranging from 1 (worst) to 10 (best) assigned by the operator. Echocardiography was conducted preoperatively, immediately after surgery, and at 30, 90, and 180 days post-implantation. At the last follow-up time point, the intervention mitral valve membrane and major organs were dissected for observation. The artificial valves were taken for hematoxylin eosin (HE) staining and observed under a scanning electron microscope. Result:All six procedures were successfully completed using 29S size TruDelta TM TMVR device. At the final follow-up, echocardiogram demonstrated good valve function without obvious paravalvular leakage, with a transvalvular gradient of (7.8±3.2) mmHg (1 mmHg=0.133 kPa) and a mitral valve orifice area of (1.8±0.2) cm 2. Autopsy findings revealed no structural valve failure and almost complete endothelialization (>75%) with 90 to 180 days. Both HE staining and scanning electron microscopy confirmed optimal endothelialization of the valve stent. Conclusion:The preclinical animal study indicates that the TruDelta TM device exhibits favorable biocompatibility and durability.

Objective:To preliminarily assess the biocompatibility and durability of the TruDelta TM transcatheter mitral valve replacement (TMVR) system. Method:Six adult sheep were divided into 3 groups based on the duration of follow-up: 30 days ( n=1), 90 days ( n=3) and 180 days ( n=2). The TruDelta TM TMVR system was implanted through a transapical approach under transesophageal echocardiographic guidance. The operability of the TMVR system was evaluated using an instrument performance evaluation scale (consisting of 39 items), with scores ranging from 1 (worst) to 10 (best) assigned by the operator. Echocardiography was conducted preoperatively, immediately after surgery, and at 30, 90, and 180 days post-implantation. At the last follow-up time point, the intervention mitral valve membrane and major organs were dissected for observation. The artificial valves were taken for hematoxylin eosin (HE) staining and observed under a scanning electron microscope. Result:All six procedures were successfully completed using 29S size TruDelta TM TMVR device. At the final follow-up, echocardiogram demonstrated good valve function without obvious paravalvular leakage, with a transvalvular gradient of (7.8±3.2) mmHg (1 mmHg=0.133 kPa) and a mitral valve orifice area of (1.8±0.2) cm 2. Autopsy findings revealed no structural valve failure and almost complete endothelialization (>75%) with 90 to 180 days. Both HE staining and scanning electron microscopy confirmed optimal endothelialization of the valve stent. Conclusion:The preclinical animal study indicates that the TruDelta TM device exhibits favorable biocompatibility and durability.

Objective To investigate the effect of mechanical stretch on the proliferation and differen-tiation of skeletal satellite cells in mice,and explore its mechanism.Methods The research was divid-ed into two parts.In the first part,all mice were not given osteogenic or adipogenic induction,and randomly divided into a control group,a mechanical stretch(MS)group,a solvent control group[Di-methyl sulfoxide(DMSO)+mechanical stretch],a Notch inhibitor(KY-02111)+mechanical stretch group and a Wnt inhibitor(FLI-06)+mechanical stretch group,with the aim to evaluate cell prolifera-tion and migration,and the effect of mechanical stretch on the Wnt and Notch signaling pathway.In the second part,all mice were randomly divided into 6 groups:a control group,an induced differentia-tion(ID)group,an induced differentiation+mechanical stretch(IDMS)group,an induced differentia-tion+DMSO+mechanical stretch(IDDMS)group,an induced differentiation+Notch inhibitor(KY-02111)+mechanical stretch(IDNMS)group,and an induced differentiation+Wnt inhibitor(FLI-06)+mechanical stretch(IDWMS)group.All groups except the control group were induced differenti-ation using osteoblastic or adipogenic medium,and the IDMS group was applied tensile stress to the cell basement membrane,with the IDDMS and IDNMS groups given DMSO and KY-02111 or FLI-06 with a final concentration of 5 μM into the culture medium,respectively.On the 7th and 14th days af-ter culture,cell proliferation was detected using CCK-8,while on the 14th day after culture,cell mi-gration was observed using the streak method.Alkaline phosphatase and oil red staining were per-formed on all cells.Moreover,the mRNA expression of osteogenic[alkaline phosphatase(ALP)and Runt-related transcription factor(Runx)-2]and adipogenic[fatty acid-binding protein(FABP)4 and li-poprteinlipase(LPL)]differentiation marker genes were quantitatively detected by using the real-time PCR.Meanwhile,while the expression of c-Myc and Cyclin B(CCNB)1 proteins was measured using Western blotting.Results Cell proliferation increased significantly in MS group compared with the con-trol group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group.As to cell migration,MS group was significantly better than the control group(P<0.01),while there was a significant decrease in both IDMMS and IDNMS groups compared with MS group(P<0.01).According to ALP and oil red staining,a significant increase in ALP activity and lipid droplet secretion was observed in skeletal muscle satellite cells of ID groups compared with the control group,with the increase in IDMMS and IDNMS groups significantly greater than MS group.More-over,the results of real-time PCR showed that the expression of ALP and Runx-2mRNA in the osteo-genic induction group and the FABP4 and LPL mRNA in the adipogenic induction group increased sig-nificantly compared with the control group(P<0.05),with a significant decrease in the above measure-ments of IDMS group compared with ID group,but a significant increase in IDMMS and IDNMS groups compared with IDMS group(P<0.01).Meanwhile,according to Western blotting,the expres-sion of c-Myc and CCNB1proteins increased significantly in the skeletal muscle satellite cells of MS group compared with the control group(P<0.01),while that of IDMMS and IDNMS groups decreased significantly compared with MS group(P<0.01).Conclusion Mechanical stretch can promote the prolif-eration and migration of skeletal satellite cells in mice,but inhibit osteogenic and adipogenic differenti-ation.Its mechanism is related to the activation of Wnt and Notch signal pathways.

Lung cancer ranks the top of malignancies that cause cancer-related deaths worldwide.The leaves of Morus alba L are traditional Chinese medicine widely applied in respiratory diseases.Our previous work has demonstrated the anti-lung cancer effect of secondary metabolites of mulberry leaf,but their mechanism of action has still not fully elucidated.We synthesized Moracin N(MAN)-Probe conjugated with alkyne to label lung cancer cells and identified protein targets by chemical proteomic analysis.MAN and its probe exerted similar growth-inhibitory effect on human lung cancer cells.Chemical proteomic results showed that MAN targeted the programmed death ligand 1(PD-L1)checkpoint pathway and T cell receptor(TCR)signaling pathway,indicating its immune-regulatory function.Cell-free surface plasmon resonance(SPR)results showed the direct interaction of MAN with PD-L1 protein.Molecular docking analysis demonstrated that MAN bound to E158 residue of PD-L1 protein.MAN downregulated the expression levels of PD-L1 in a time-and dose-dependent manner and disrupted the PD-L1/programmed death 1(PD-1)binding,including other secondary metabolites of mulberry leaves Guangsangon E(GSE)and Chalcomoracin(CMR).Human peripheral blood mononuclear cells(PBMCs)co-cultured with MAN-treated A549 cells,resulting in the increase of CD8+GZMB+T cells and the decrease of CD8+PD-1+T cells.It suggested that MAN exerts anti-cancer effect through blocking the PD-L1/PD-1 signaling.In vivo,MAN combined with anti-PD-1 antibody significantly inhibited lung cancer development and metastasis,indicating their synergistic effect.Taken together,secondary metabolites of mulberry leaves target the PD-L1/PD-1 signaling,enhance T cell-mediated immunity and inhibit the tumorigenesis of lung cancer.Their modulatory effect on tumor microenvironment makes them able to enhance the therapeutic efficacy of immune checkpoint inhibitors in lung cancer.

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.

Objective:To analyze the long-term outcomes of different secondary surgeries in women with recurrent stress urinary incontinence (SUI) after Burch colposuspension.Methods:Between February 2004 to February 2010, five women with recurrent SUI after Burch colposuspension in Peking Union Medical College Hospital were retrospectively followed up, and the long-term outcomes of secondary surgeries were analyzed. Subjective cures of Burch colposuspension and secondary surgeries were assessed by patients′ self-reported incontinence symptoms and patient global impression of improvement questionnaire; objective cure, improvement or failure were determined by 1-hour pad test.Results:Three women underwent tension-free vaginal tape-retropubic (TVT) as the secondary surgery, one underwent tension-free vaginal tape-obturator (TVT-O), and one underwent single-incision tension-free vaginal tape-Secur (TVT-Secur). The follow-up period of five women was (14.6±2.4) years (range: 10.8 to 16.9 years). Three women undergoing TVT secondary surgery were subjectively cured; while the other two women undergoing TVT-O or TVT-Secur were not subjectively cured, but the woman undergoing TVT-O was objectively improved.Conclusions:It is feasible for women with recurrent SUI after Burch colposuspension to receive the secondary surgery. Our limited data suggests that TVT could be considered.

Objective:To analyze the correlation between simple thyroid nodule and blood lipid and glucose metabolism and iodine nutrition level.Methods:A cross-sectional study was conducted by collecting data of the population undergoing epidemiological investigation in Jinshan District, Shanghai from July to December 2015, to calculate the prevalence of thyroid nodules and analyze relevant functional indicators.Results:Simple thyroid nodules were detected in 603 subjects, with a prevalence of 22.6% (603/2 669). There were 358 female patients with simple thyroid nodules, with a prevalence rate of 26.9%, and 245 male patients with simple thyroid nodules, with a prevalence rate of 18.3%. The prevalence of simple thyroid nodule in female was higher than that in male, and the difference was statistically significant (χ 2=27.686, P<0.001). In addition, the prevalence of simple thyroid nodules increased with age (13.1% (92/704) and 20.2% (104/514) and 25.1% (145/578) and 24.4% (107/439) and 36.3% (98/270) and 34.8% (57/164), χ 2=83.872,P<0.001). In the ≤30 years group (8.0% (30/704) vs. 18.8% (62/331), χ 2=35.716, P<0.001), >30 to ≤40 years old group (14.1% (37/263) vs. 26.7% (67/251), χ 2=12.683, P<0.001), >60 to ≤70 years old group (26.2% (33/126) vs. 45.1% (65/144), χ 2=10.435, P<0.001), and the 70-year-old group (24.4% (21/86) vs. 46.2% (36/78), χ 2=8.521, P<0.001). The prevalence of simple thyroid nodules in males was lower than that in females. In the simple positive thyroid nodule group, Fasting blood glucose (5.12 (4.80, 5.69) and 5.02 (4.72, 5.48)), total cholesterol (1.24 (0.85, 1.86) and 1.13 (0.77, 1.76)), triglyceride (4.77 (4.09, 5.48) and 4.49 (3.92, 5.16)), low density lipoprotein((2.79 (2.26, 3.36) and 2.63 (2.19, 3.16)), and high density lipoprotein cholesterol (1.41 (1.18, 1.66) and 1.35 (1.13, 1.61)) were higher than those in the negative group ( U values were 554 818, 578 468, 535 622, 556 067 and 567 960, respectively, all P<0.01). The BMI index grade distribution of thyroid nodule positive group was higher than that of negative group, and the difference was statistically significant (3.7% (77/2 066), 50.1% (1 034/2 066), 32.4% (669/2 066), 13.8% (286/2 066), 3.2% (19/603), 43.6% (263/603), 38.1% (230/603), 15.1% (91/603), χ2=9.5201, P=0.023). The prevalence of simple thyroid nodules was significantly lower in the iodized salt group than in the non-iodized salt group (20.7% (436/2 102) vs. 29.5% (167/567), χ 2=19.376, P<0.001). The urinary iodine level in the positive thyroid nodule group was significantly lower than that in the negative group (148.4(100.2, 213.7) vs. 169.5(115.4, 241.75), U=545 129.5, P<0.001). After Logistic regression screening, age ( OR=1.57, 95% CI: 1.292-1.908, P<0.001), gender ( OR=1.278, 95% CI: 1.193-1.368, P<0.001), BMI grade ( OR=1.166, 95% CI: 1.022-1.330, P=0.022), total cholesterol ( OR=1.105, 95% CI: 1.005-1.214, P=0.040), iodized salt ( OR=0.689, 95% CI: 0.556-0.854, P=0.001) were independent influencing factors of thyroid nodule. Conclusion:The prevalence of simple thyroid nodules in Shanghai is relatively low. Age, sex, BMI level, total cholesterol and iodized salt are independent factors causing thyroid nodules. In addition, blood glucose level may also be related to the prevalence of thyroid nodules.

Objective:To investigate the clinical value of free-talk language functional cortex mapping methods based on high frequency response in epileptic foci resection.Methods:Twenty patients with intractable epilepsy admitted to our hospital from January 2016 to May 2019 were chosen in our study. According to the different intraoperative mapping methods of language functional region, these patients were divided into test group ( n=10, using free-talk language function localization based on high frequency response [new method]+ electrical cortical stimulation [ECS]) and control group ( n=10, using ECS localization only). The overlap rate of the two methods in the test group were calculated and the postoperative follow-up results of patients in the two groups were analyzed. Results:In 10 patients from the test group, 33 positive loci in the Broca's area and 33 positive loci in the Wernicke's area were detected by new method; at the meantime, 16 positive loci in the Broca's area and 8 positive loci in the Wernicke's area were detected by ECS method, which had a overlap rate of 93.75% (15/16) in the Broca's area and 75.00% (6/8) in the Wernicke's area, respectively, as compared with the new method. In the 10 patients from the control group, 18 positive loci in the Broca's area and 3 positive loci in the Wernicke's area were detected by ECS method. In the test group, 7 patients achieved Engel grading I and 2 patients developed transient language function impairment after surgery; while in the control group, 5 patients achieved Engel grading I and 4 patients developed transient language function impairment after surgery.Conclusion:The new method has a high overlap rate with ECS method; the combination of the two methods can help to decrease the speech function impairment after excision of epileptogenic foci in patients with epilepsy.