Objective To investigate the impact of cardiomyocyte ferroptosis on acute myocardial infarction(AMI)and its relationship with the expression of long non-coding RNA(lncRNA)GAS5.Methods An AMI model was established in eighteen male SD rats(6-8 weeks old),and then the subjected rats were randomly divided into blank control group,sham operation group,and model group,6 animals in each group.In 2 weeks after surgery,echocardiography was used to evaluate heart function,and TTC staining,HE staining and TUNEL staining were employed re-spectively to observe myocardial infarct area,histopathological changes of myocardial tissues and apoptosis in cardiomyocytes.Serum Fe2+concentration was measured with an iron ion detection kit.The expression levels of lncRNA GAS5,nuclear factor erythroid-derived 2-like 2(Nrf2),and glutathione peroxidase 4(GPX4)in myocardial tissues were detected with QT-PCR.Linear corre-lation analysis was performed to investigate the relationship between the expression of lncRNA GAS5,Nrf2 and GPX4 with Fe2+concentration.Western blotting was conducted for the protein levels of ferroptosis-related proteins,glutathione peroxidase 4(GPX4),nuclear factor erythroid-derived 2-like 2(Nrf2),glucose-regulated protein 78(GRP78),and cysteinyl aspartate specific proteinase 12(Caspase-12)in myocardial tissues.Results Western blotting revealed obvious in-creases in the protein levels of ferroptosis related proteins GRP78(1.11±0.13 vs 0.51±0.08,P＜0.01)and Caspase-12(1.23±0.05 vs 0.92±0.07,P＜0.05)and a decrease in those of ferroptosis inhibitor GPX4(0.27±0.11 vs 0.68±0.10,P＜0.01)and Nrf2(0.30±0.12 vs 0.58±0.04,P＜0.05)in the model group than the sham operation group.Additionally,QT-PCR showed that the mRNA levels of GPX4 and Nrf2 were notably lower,indicating cardiomyocyte ferroptosis,while that of lncRNA GAS5 was remarkably higher in the myocardial tissues of the model group than the sham operation group(P＜0.01).What's more,the expression of lncRNA GAS5 had a positive correlation with serum Fe2+concentration(P＜0.05).Conclusion AMI is closely associated with cardiomyocyte ferroptosis.lncRNA GAS5 is involved in the regulation of ferroptosis by Nrf2/GPX4 signaling pathway,which thus mediating the occurrence of heart failure after AMI.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

Objective:To explore the characteristics of renal oxidative stress injuries in rats with high-voltage electric burns and the intervention effects of breviscapine.Methods:This study was an experimental study. One hundred and sixty 8-10-week-old male Sprague Dawley rats were divided into sham injury group, electric burn group, saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, with 60 rats in each of the sham injury group and electric burn group, 10 rats in each of the other 4 groups, respectively. The rats in sham injury group and electric burn group were divided into 10 rats at each time point, including post injury hour (PIH) 0 (immediately), 8, 24, 48, and 72, and post injury week (PIW) 1. The rats in sham injury group were not conducted with electrical current to cause sham injury. The rats in the other 5 groups were caused high-voltage electric burns. The rats in sham injury group and electric burn group were not treated after injury. The rats in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group were intraperitoneally injected with 5 mL/kg normal saline or 0.4, 1.6, and 4.0 g/L breviscapine, repeated every 24 h until PIH 72. After the model was successfully made, 14 rats died, including 1, 2, 2, and 1 rat (s) at PIH 24, 48, and 72 and PIW 1 in electric burn group, 4, 1, 2, and 1 rat (s) at PIH 72 in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group, respectively. The kidney tissue collected from rats in the 6 groups was weighed and the kidney/body weight ratio was calculated. The left upper pole tissue of kidney was collected from each 4 rats in sham injury group, and in electric burn group at PIH 8, 24, 48, and 72 and PIW 1, and in saline group, low breviscapine group, middle breviscapine group, and high breviscapine group at PIH 72. The renal tubular and renal interstitial injury was evaluated by a semi-quantitative histological scoring system after hematoxylin-eosin staining. The inferior vena cava blood samples were collected from rats in the 6 groups to measure the serum creatinine levels via sarcosine oxidase method, and serum urea nitrogen levels via urease method. The right renal cortices were collected from rats in the 6 groups to measure the catalase (CAT) activity in the supernatant of renal tissue via molybdic acid method, and the levels of advanced oxidation protein product (AOPP) and Klotho protein in the supernatant of renal tissue via enzyme-linked immunosorbent assay.Results:At PIH 8, 48, and 72 and PIW 1, the kidney/body weight ratios of rats in electric burn group were significantly higher than those in sham injury group (with t values of -0.52, -3.75, -4.05, and -2.25, respectively, P<0.05). At PIH 72, compared with those in electric burn group, saline group, low breviscapine group, and middle breviscapine group, the kidney/body weight ratio of rats in high breviscapine group was significantly decreased (with P values all <0.05). Compared with those in sham injury group, the renal tubular and renal interstitial injury scores of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly increased ( P<0.05). Compared with those in electric burn group at PIH 8 and 24, the renal tubular and renal interstitial injury score of rats in electric burn group at PIW 1 was significantly increased (with P values all <0.05). At PIH 72, the renal tubular and renal interstitial injury scores of rats in the 5 groups of rats with electric burns were similar ( P>0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of serum creatinine and serum urea nitrogen of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -2.37, -2.62, -2.67, -3.67, -2.34, -3.11, -3.43, -3.11, and -3.51, respectively, P<0.05). Compared with that in electric burn group at PIH 0, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 8, the levels of serum creatinine of rats in electric burn group at PIH 72 and PIW 1 were significantly increased ( P<0.05). Compared with that in electric burn group at PIH 24, the level of serum creatinine of rats in electric burn group at PIW 1 was significantly increased ( P<0.05). At PIH 72, the levels of serum creatinine of rats in the 5 groups of rats with electric burns were similar ( P>0.05). Compared with that in electric burn group, the levels of serum urea nitrogen of rats in low breviscapine group, middle breviscapine group, and high breviscapine group were significantly decreased ( P<0.05). Compared with that in saline group, the levels of serum urea nitrogen in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). At PIH 48 and 72 and PIW 1, the CAT activities in the supernatant of renal tissue of rats in electric burn group were significantly lower than those in sham injury group (with Z values of -2.22, -2.13, and -3.51, respectively, P<0.05). At PIH 8, 24, 48, and 72 and PIW 1, the levels of AOPP in the supernatant of renal tissue of rats in electric burn group were significantly higher than those in sham injury group (with Z values of -2.00, -3.15, -2.71, -2.04, and -2.33, respectively, P<0.05). At PIH 0-PIW 1, the levels of Klotho protein in the supernatant of renal tissue of rats in sham injury group and electric burn group were all similar ( P>0.05). Compared with that in electric burn group at PIH 0, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 8, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 and the levels of Klotho protein in the supernatant of renal tissue of rats in electric burn group at PIH 48 and 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 24, the CAT activities in the supernatant of renal tissue of rats in electric burn group at PIH 72 and PIW 1 were significantly decreased ( P<0.05). Compared with that in electric burn group at PIH 48, the CAT activity in the supernatant of renal tissue of rats in electric burn group at PIW 1 was significantly decreased ( P<0.05). At PIH 72, the levels of Klotho protein in the supernatant of renal tissue of rats in the 5 groups of rats with electric burns were similar ( P<0.05). Compared with 14.6 (12.6, 23.6) U/mgprot in electric burn group, the CAT activities in the supernatant of renal tissue of rats in low breviscapine group (20.5 (18.0, 39.8) U/mgprot), middle breviscapine group (24.9 (14.7, 28.9) U/mgprot), and high breviscapine group (28.0 (21.9, 39.1) U/mgprot) were significantly increased ( P<0.05). Compared with 15.7 (13.7, 25.6) U/mgprot in saline group, the CAT activities in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly increased ( P<0.05). Compared with that in low breviscapine group, the CAT activity in the supernatant of renal tissue of rats in high breviscapine group was significantly increased ( P<0.05). Compared with those in electric burn group and saline group, the levels of AOPP in the supernatant of renal tissue of rats in middle breviscapine group and high breviscapine group were significantly decreased ( P<0.05). Conclusions:After high-voltage electric burns, oxidative stress injury occur in the kidneys of rats, which is aggravated with time extension. Breviscapine can alleviate oxidative stress injuries in the kidneys of rats with high-voltage electric burns.

Objective To observe the efficacy of gray-scale ultrasound-based radiomics for differentiating peripheral pulmonary adenocarcinoma and squamous cell carcinoma.Methods Data of 88 patients with single peripheral lung adenocarcinoma and 58 patients with single peripheral lung squamous cell carcinoma proved pathologically with puncture biopsy and clearly visualized with lung ultrasound were retrospectively analyzed.The patients were divided into training set(n=103)and test set(n=43)at the ratio of 7:3.Based on gray-scale ultrasound of training set,radiomics features associated with differential diagnosis of peripheral lung adenocarcinoma and lung squamous cell carcinoma were extracted and screened.Using 4 different classifiers,including support vector machine(SVM),linear discriminant analysis(LDA),logistic regression(LR)and the least absolute shrinkage and selection operator combined with logistic regression(LASSO-LR),4 corresponding radiomics models were obtained,and the relative best models were selected according to their performances under 10-fold cross validation.The receiver operating characteristic curves were drawn,the areas under the curve(AUC)were calculated to evaluate the differentiating efficacy of each model,and DeLong test was used for the comparison.The differentiating accuracy of models were obtained under the best cutoff value with the maximum Youden index.Results The AUC of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous carcinoma in test set was 0.864,0.867,0.880 and 0.844,respectively,and no significant difference was found among 4 models(all P＞0.05).Under the best cutoff value of each model,the corresponding accuracy of SVM,LDA,LR and LASSO-LR radiomics models for differentiating peripheral lung adenocarcinoma and lung squamous cell carcinoma was 86.05％,83.72％,88.37％and 86.05％,respectively.Conclusion Radiomics models based on gray-scale ultrasound could be used to differentiate peripheral lung adenocarcinoma and lung squamous cell carcinoma.

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To analyze the current status and hotspots of surgical transmural ablation of atrial fibrillation using CiteSpace and VOSviewer. Methods The Web of Science Core Collection database was used as the data source. The CiteSpace 5.8.R3 and VOSviewer software were used to analyze the related studies on surgical transmural ablation of atrial fibrillation about the authors, countries/institutions, literature co-citation and keywords. Results A total of 109 articles were enrolled. Damiano RJ was the most prolific researcher, while Cox JL was the author with the highest number of citations. The United States was the leading country in this research field. The University of Washington was an important institution in the study of atrial fibrillation transmural ablation. The main hotpots were the effectiveness of surgical ablation, especially Cox-maze procedure, selection of the energy source of surgical ablation, combination of surgical and catheter ablations, and pulmonary vein isolation. Conclusion This study visualizes the current research status of surgical ablation of atrial fibrillation. How to improve the effectiveness and transmurality of surgical ablation is a hot research topic in the surgical treatment of atrial fibrillation. The combination of electrophysiology mapping and surgical ablation may be the development direction in the surgical treatment of atrial fibrillation.

【Objective】 To investigate the efficacy and safety of 450 nm blue laser with 6 o’clock positioning in the treatment of middle lobe hyperplasia of prostate, in order to promote the clinical application of this surgery. 【Methods】 Clinical data of 20 patients with middle lobe hyperplasia of prostate treated with 450 nm blue laser with 6 o’clock positioning during Mar.and Aug.2023 were retrospectively analyzed.The operation time, postoperative bladder irrigation time, catheter indwelling time, hospital stay, and complications were recorded.The maximum urinary flow rate (Qmax), post-void residual volume (PVR), quality of life scale (QoL), international prostate symptom score (IPSS) before surgery and 1 month after surgery were compared. 【Results】 The operation time was (26.80±7.22) min, and bladder irrigation time was (20.50±1.79) h.The catheter was removed on the next day after surgery and all patients were discharged 2 days after operation.Compared to preoperative, one month after surgery, the Qmax [(7.40±1.05) mL/s vs.(19.60±1.76) mL/s] was significantly higher, PVR [(73.50±12.26) mL vs.(9.25±4.94) mL], QoL [(4.55±1.19) vs.(1.95±0.95)], and IPSS [(26.55±1.88) vs.(10.05±1.36)] were significantly lower, the differences being statistically significant (P<0.05).No complications occurred during operation and 1-month follow-up. 【Conclusion】 The 450 nm blue laser with 6 o’clock positioning is a new, safe and effective surgical treatment of middle lobe hyperplasia of prostate, which is worthy of clinical promotion and application.

Objective:To investigate the therapeutic effect and potential molecular mechanisms of cyclin-dependent kinase inhibitor-73 (CDKI-73), the Rab11 inhibitor, on liver fibrosis.Methods:Human LX2 cells were divided into four groups: negative control group, transforming growth factor-β (TGF-β) group, CDKI-73 group and TGF-β+ CDKI-73 group. Fifteen 5-week-old female C57 mice with body weight of (18.04±0.62) g were divided into 3 groups with 5 mice in each group: control group (intraperitoneal injection of olive oil + vehicle gavage), carbon tetrachloride (CCl 4) group (intraperitoneal injection of CCl 4 + vehicle gavage) and CCl 4+ CDKI-73 group (intraperitoneal injection of CCl 4+ CDKI-73 gavage). Another 15 5-week-old female C57 mice with body weight of (18.06±0.34) g were divided into 3 groups with 5 mice in each group: sham operation group (Sham), bile duct ligation (BDL) group + vehicle group (BDL+ vehicle gavage) and bile duct ligation+ CDKI-73 group (BDL+ CDKI-73 gavage). The expression of α-smooth muscle actin (α-SMA) and fibronectin(FN)in LX2 cells were analyzed by Western blot. Masson and Sirius red were used to examine the liver fibrosis after CDKI-73 treatment in vivo. Immunohistochemistry (IHC) was utilized to examine the expression of α-SMA in mice liver. Results:Collagen content assessed by Sirius red and Masson staining and α-SMA expression evaluated by IHC were all increased in CCl 4 group compared with control group ( q=38.47, 24.99, 36.79). Moreover, the collagen content and α-SMA expression in CCl 4 + CDKI-73 treatment group were obviously decreased compared with CCl 4 group ( q=24.72, 14.87, 27.50), and the differences were statistically significant (all P<0.001). Compared with Sham group, collagen content and α-SMA expression in bile duct ligation group were increased ( q=28.23, 41.01, 44.16). Furthermore, in BDL group, after treatment with CDKI-73, the collagen content and α-SMA expression were notably decreased ( q=22.88, 34.31 and 33.97, all P<0.001). Consistent with in vivo results, the relative expression levels of α-SMA and FN protein in TGF-β group were higher than those in TGF-β+ CDKI-73 group (α-SMA: 3.71±0.34 vs. 1.28±0.31; FN: 3.21±0.39 vs. 0.83±0.06, all P<0.001). The mRNA relative expression levels of α-SMA and FN in TGF-β group were higher than those in TGF-β+ CDKI-73 group, and the differences were statistically significant ( P<0.001). However, the relative expression of TGF-β receptor Ⅱ protein in CDKI-73 group was higher than those in negative control group (4.68±0.63 vs. 1.00±0.22, P=0.004). The relative expression level of phosphorylated SMAD2 in TGF-β+ CDKI-73 group was lower than those in TGF-β group (1.67±0.24 vs. 3.99±0.44, P<0.001). Transwell assay showed that 0.5 μmol/L CDKI-73 could effectively inhibit the migration of LX2 cells, and the inhibitory ability became stronger with the increase of CDKI-73 concentration. Conclusion:CDKI-73 can inhibit the activation of hepatic stellate cells and liver fibrosis by inhibiting Rab11-dependent TGF-β signaling pathway both in vivo and in vitro.

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
Mice ; Animals ; Ependymoglial Cells/physiology* ; Cadherins ; Neurons/metabolism* ; Cerebral Cortex/metabolism* ; Cell Differentiation ; Cell Movement

After continuous efforts from generations of transplant surgeons, kidney transplantation (KT) has become an optimal treatment for end-stage renal disease.However, an imbalance between supply and demand of organs has always restricted the development of KT.For this clinical dilemma, xenotransplantation is expected to become one practical alternative for alleviating organ shortage.This review summarized recent literature reports of kidney xenotransplantation and the latest cases of pig-to-human kidney and heart transplantations.Also clinical transformations and applications of kidney xenotransplantation were discussed.