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Abstract The scarcity of suitable high-throughput screening technology for hydrogen sulfide (H2S) donors has hampered the discovery of H2S donors. In this study, a long-lived cyclometalated iridium complex was rationally designed as a mitochondria-targeted H2S probe to monitor the real-time dynamic change of H2S. By using the time-resolved emission spectroscopy (TRES) technique, an anti-interference high-throughput screening system was developed to monitor H2S in living cells with decreased false negative results. As a proof-of-concept, three natural products were identified as potential H2S donors from a natural product library using the developed TRES probe. Notably, the discovery of allicin and diallyl trisulfide demonstrated the feasibility of this screening platform, while garlic-derived allyl methyl sulfide was explored as a H2S donor candidate. The results were further validated by a commercial assay. We anticipate this high-throughput platform could facilitate the discovery of H2S donors by discriminating the endogenous interfering fluorescence from biological systems.

Abstract The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P

Based on the renewable portfolio standard and carbon cap-and-trade scheme, consumers faced with the demand of power and carbon emission permits shall be able to participate in three markets, i.e., green power market, electricity market and carbon market. In this paper, we propose a two-step energy trading approach to help consumers optimize their utility, considering the conflict of interest regarding whether to purchase power from the aforementioned three markets and how much power to purchase from each market. This approach takes into account several factors, including the benefits of participating in demand response, the costs associated with consumer dissatisfaction, the costs of power purchased from the electricity market, the costs of renewable power purchased from the green power market, and the costs of carbon emission permits purchased from the carbon market. The two-step formulation establishes an equilibrium problem with equilibrium constraints. A chance-constrained optimization method is utilized due to the uncertain fluctuation of renewable power in the two steps. The equilibrium problem with equilibrium constraints in the two steps can be settled by the nonlinear optimization of multiple subproblems with corresponding Karush-Kuhn-Tucker conditions. Simulations show that the proposed approach is able to significantly improve the utility of the consumers in the energy trading process among green power, electricity and carbon markets.

Background: It is controversial when surgery should be performed for pectus excavatum (PE). The study retrospectively compared the long-term prognosis in PE children undergoing the Nuss procedure at the age of 4–6 versus those performing surgery at the age of 12–14. Methods: 178 patients were included in the retrospective real-world research. Clinical Characteristics were collected at baseline. The endpoint of the study was set as the last follow-up at the age of 18 in outpatient services. Satisfaction and complication rate were set as the primary outcome and were collected at the endpoint. Hospital stay post-surgery and analgesia dosage were regard as the secondary outcome. To reduce potential bias between two different age groups, propensity score matching (PSM) analysis was analysized. Results: The oral analgesic dosage of children in the 4–6 years old age group is significantly lower than that of the 12–14 years old group (0.70/kg, 0.30–1.50/kg versus 1.50/kg, 0.90–2.30/kg, P

Abstract Background Diabetic nephropathy (DN) is a diabetic complication. LncRNAs are reported to participate in the pathophysiology of DN. Here, the function and mechanism of lncRNA small nucleolar RNA host gene 14 (SNHG14) in DN were explored. Methods Streptozotocin (STZ)‐induced DN mouse models and high glucose (HG)‐treated human mesangial cells (MCs) were used to detect SNHG14 expression. SNHG14 silencing plasmids were applied to examine the function of SNHG14 on proliferation and fibrosis in HG‐treated MCs. Potential targets of SNHG14 were predicted using bioinformatics tools and verified by luciferase reporter, RNA pulldown, and northern blotting assays. The functional role of SNHG14 in DN in vivo was detected by injection with adenoviral vector carrying sh‐SNHG14 into DN mice. Serum creatinine, blood urea nitrogen, blood glucose, 24‐h proteinuria, relative kidney weight, and renal pathological changes were examined in DN mice. Results SNHG14 expression was elevated in the kidneys of DN mice and HG‐treated MCs. SNHG14 silencing inhibited proliferation and fibrosis of HG‐stimulated MCs. SNHG14 bound to miR‐30e‐5p to upregulate SOX4 expression. In rescue assays, SOX4 elevation diminished the effects of SNHG14 silencing in HG‐treated MCs, and SOX4 silencing reversed the effects of SNHG14 overexpression. In in vivo studies, SNHG14 downregulation significantly ameliorated renal injuries and renal interstitial fibrosis in DN mice. Conclusions SNHG14 silencing attenuates kidney injury in DN mice and reduces proliferation and fibrotic phenotype of HG‐stimulated MCs via the miR‐30e‐5p/SOX4 axis.

Background Left ventricular opacification (LVO) improves the accuracy of left ventricular ejection fraction (LVEF) by enhancing the visualization of the endocardium. Manual delineation of the endocardium by sonographers has observer variability. Artificial intelligence (AI) has the potential to improve the reproducibility of LVO to assess LVEF. Objectives The aim was to develop an AI model and evaluate the feasibility and reproducibility of LVO in the assessment of LVEF. Methods This retrospective study included 1305 echocardiography of 797 patients who had LVO at the Department of Ultrasound Medicine, Union Hospital, Huazhong University of Science and Technology from 2013 to 2021. The AI model was developed by 5-fold cross validation. The validation datasets included 50 patients prospectively collected in our center and 42 patients retrospectively collected in the external institution. To evaluate the differences between LV function determined by AI and sonographers, the median absolute error (MAE), spearman correlation coefficient, and intraclass correlation coefficient (ICC) were calculated. Results In LVO, the MAE of LVEF between AI and manual measurements was 2.6% in the development cohort, 2.5% in the internal validation cohort, and 2.7% in the external validation cohort. Compared with two-dimensional echocardiography (2DE), the left ventricular (LV) volumes and LVEF of LVO measured by AI correlated significantly with manual measurements. AI model provided excellent reliability for the LV parameters of LVO (ICC > 0.95). Conclusions AI-assisted LVO enables more accurate identification of the LV endocardium and reduces observer variability, providing a more reliable way for assessing LV function.

Primary lung cancer in childhood is extremely rare, with an incidence rate of less than 2/100,0000, and pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. Their symptoms are usually not specific, and there are no guidelines for their management, which makes their clinical management a challenge for pediatricians. The purpose of this report is to discuss the clinical presentation, positive signs, examinations, pathological characteristics, surgical modalities, chemotherapy regimens, and prognosis in children. The clinical data of four patients diagnosed with PMEC at the Children’s Hospital of Chongqing Medical University from June 2021 to November 2022 were retrospectively analyzed, and their clinical features, treatment, and prognosis were summarized. Among them, two were male and two were female; their ages ranged from 3 years and 10 months to 10 years and 11 months, and all were staged according to tumor node metastasis classification (TNM). Immunohistochemical tests were performed in all children, among which four cases were positive for cytokeratin (CK), two cases were positive for CK7, four cases were positive for p63, about 5–10% of tumor cells were positive for Ki67. Among the four children, three had surgery alone and one had surgery + chemotherapy. All four children are presently living, with no evidence of tumor recurrence or metastasis. PMEC in children is very rare, and its age of onset and symptoms are not specific, and there is no obvious correlation with gender. Its diagnosis mainly relies on pathomorphological diagnosis, and immunohistochemical detection has no specific performance. The prognosis of children with PMEC is related to the clinical stage and whether surgery is performed. Whether further chemotherapy or radiotherapy is needed for patients who cannot undergo surgical resection and for those who have a combination of distant metastases requires further clinical studies.

Introduction: It has been shown that polystyrene nanoplastic (PS-NP) exposure induces toxicity in the lungs. Objectives: This study aims to provide foundational evidence to corroborate that ferroptosis and abnormal HIF-1α activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure. Methods: Fifty male and female C57BL/6 mice were exposed to distilled water or 100 nm or 200 nm PS-NPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100 μg/ml, 200 μg/ml and 400 μg/ml 100 or 200 nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24 h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1α/HO-1 signaling pathway activity. Results: H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1α/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury. Conclusion: PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1α/HO-1 signaling pathway, and eventually led to lung injury.

Background: Pediatric bronchiectasis is a common respiratory disease in children. The use of video-assisted thoracoscopic surgery (VATS) for its treatment remains controversial. Objectives: The objective of our study was to compare and analyze the clinical efficacy of thoracoscopic surgery and thoracotomy in the treatment of pediatric bronchiectasis and summarize the surgical treatment experience of VATS in children with bronchiectasis. Design: Retrospective single-center cohort study. Methods: A retrospective analysis was conducted on the clinical data of 46 pediatric patients who underwent surgery with bronchiectasis at the Children’s Hospital of Chongqing Medical University from May 2015 to May 2023. The patients were divided into two groups: the VATS group (25 cases) and the thoracotomy group (21 cases). Comparative analysis was performed on various parameters including basic clinical data, surgical methods, operation time, intraoperative blood loss, transfusion status, postoperative pain, postoperative mechanical ventilation time, chest tube drainage time, length of hospital stay, incidence of complications, and follow-up information. Results: There were no statistically significant differences between the two groups of patients in terms of age, weight, gender, etiology, duration of symptoms, site of onset, and comorbidities ( p > 0.05). The operation time in the VATS group was longer than that in the thoracotomy group ( p

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation-mediated chronic low-grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome-based therapies for drug delivery vehicles, and targeted therapy for exosomes.

The purpose of this study was to evaluate the effect of laser parameters on the fatigue crack growth (FCG) behavior of AZ31B Magnesium alloy TIG welded bionic joints with ‘soft-hard’ alternating structures prepared by laser bionic treatment (LBT). The changes of laser parameters promoted the growth of fine equiaxed grain with random texture, and average grain size was 5.12 ± 0.51–8.19 ± 1.02 μm, which significantly increased isotropy and microhardness. The average microhardness was 66.5 ± 1.68–70.85 ± 1.41 HV0.1, which increased by more than 23.11% compared with untreated welded joints. For bionic welded joints, the heat-affected zone (HAZ) had higher FCG resistance and cycle times than weld metal (WM), and the specimens with notch in the HAZ showed obvious crack deflection. It was found that FCG behavior showed significant microstructure sensitivity by comparing the FCG rate curve and crack opening displacement. The Paris parameters had a significant linear relationship and effectively reflect the FCG resistance of the different specimens. The fatigue fracture showed that the crack growth zone was mainly dominated by typical cleavage steps and secondary cracks. The fatigue fracture region contains quasi-cleavage and ductile fracture. A series of strengthening mechanisms were induced by LBT and could significantly affect FCG behavior, which promoted crack deflection and branching to increase the toughness of the joint, while the laser remelting zone increased the strength of the joint. Therefore, the synergistic effect of strength-toughness of the joint was obtained by LBT, which provided a new idea for optimizing the bionic design and improving the fatigue property of welded joints.

Abstract Background Primary cardiac tumors are rare, and cardiac myxoma (CM) accounts for the majority of these tumors. Most of the reports in the literature are case reports. This study summarizes our clinical experience in the surgical treatment of CM over the past 12 years. Methods We retrospectively analyzed the clinical data of 23 children with CM(8 boys, 15 girls; median age: 8.92 months, range: 2 years 5 months-12 years 9 months; body weight: 11-45 kg, median body weight: 28.21 kg) admitted to our hospital in the previous 12 years, and we statistically analyzed their clinical manifestations and surgical methods. Results 23 cases underwent myxoma excision under cardiopulmonary bypass(CPB). The follow-up period was 0.2 to 12.6 years (mean:7.2 years). Two patients could not be traced, and the follow-up completion rate was 91.30%. One patient (4.35%) died of myocardial infarction early after surgery with low continuous cardiac output. There were no cerebral embolism, acute heart failure, atrioventricular block and other related complications in 19 cases. A patient with cerebral infarction complicated with right hemiplegia recovered well after rehabilitation treatment. There was no recurrence of CM in 19 cases and all patients recovered after surgery. One patient relapsed 5 years after surgery, and no tumor recurrence was observed after the second surgery. Among the 20 long-term survivors, 13 (65.00%) were NYHA Class I patients and 7(35.00%) were NYHA Class II patients. Conclusions Although CM in children is rare, it may cause cerebral infarction and other multi-organ embolism. Once CM is found and removed as soon as possible, it can reduce serious complications. If the complete resection is possible, surgery provides better palliation. Follow-up echocardiographic should be paid attention to after surgery.

Abstract Background AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy. Methods During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP])

Abstract Objectives A retrospective study was performed to summarize the experience of transcatheter closure of patent ductus arteriosus (PDA) through the right femoral vein under the guidance of transesophageal echocardiography (TEE). Methods From January 2019 to September 2021, 75 children who underwent PDA closure through the right femoral vein under the guidance of TEE were included. The guide wire and delivery sheath were inserted through the ductus arteriosus into the descending aorta via the right femoral vein, and the occluder was subsequently deployed. After discharge, all patients were required for outpatient follow-ups at 1, 3, 6 and 12 months. Results In this group, patients were older than 10 months of age and body weight greater than 8 kg. Among 75 cases with PDA, 63 were tubular type and 12 were conical type. The mean operative time was 40.2 ± 7.3 min. The size of PDA occluder ranged from 4–6 to 12–14 mm. The mean hospital stay was 5.5 ± 0.5 days. One month after discharge, there were 4 cases with a mild residual shunt. Eventually, the residual shunt was not observed during 3, 6, and 12 months of follow-up. Conclusions PDA closure under the guidance of TEE can be performed through the right femoral vein successfully and effectively. This procedure has no contrast agent usage, radiation exposure, or open incisions.

Abstract Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT.

Abstract Background This study aimed to evaluate the effectiveness of video-assisted thoracic surgery for the treatment of congenital diaphragmatic hernia (CDH) in a larger series compared with conventional open surgery. Additionally, we summarized the experience of thoracoscopic surgery in the treatment of CDH in infants. Methods We retrospectively analysed the clinical data of 109 children with CDH who underwent surgical treatment at the Department of Cardiothoracic Surgery of Children’s Hospital of Chongqing Medical University from January 2011 to January 2021. According to the surgical method, the children were divided into an open group (62 cases) and a thoracoscopy group (47 cases).Patients who underwent surgical correction had the diaphragmatic defect size graded (A–D) using a standardized system. We compared the operation time, intraoperative blood loss, postoperative mechanical ventilation time, postoperative hospital stay, postoperative CCU admission time and other surgical indicators as well as the recurrence rate, mortality rate and complication rate of the two groups of children. Results The index data on the operation time, intraoperative blood loss, postoperative mechanical ventilation time, postoperative hospital stay and postoperative CCU admission time were better in the thoracoscopy group than in the open group. The difference between the two groups was statistically significant (P

Abstract Background Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined. Methods Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin–neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5′-untranslated region (5′-UTR)-mediated translation was analyzed using a dual luciferase reporter system. Conclusion We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5′-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5′-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

Abstract RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active form of the popular drug remdesivir (RTP) and adenosine triphosphate (ATP) by utilizing high-throughput virtual screening (HTVS) against the vast ZINC compound database coupled with extensive molecular dynamics (MD) simulations. After post-trajectory analysis, we found that the simulations of complexes containing both ATP and RTP remained stable for the duration of their trajectories. Additionally, it was revealed that the phosphate tail of RTP was stabilized by both the positive amino acid pocket and magnesium ions near the entry channel of RdRp which includes residues K551, R553, R555 and K621. It was also found that residues D623, D760, and N691 further stabilized the ribose portion of RTP with U10 on the template RNA strand forming hydrogen pairs with the adenosine motif. Using these models of RdRp, we employed them to screen the ZINC database of ~ 17 million molecules. Using docking and drug properties scoring, we narrowed down our selection to fourteen candidates. These were subjected to 200 ns simulations each underwent free energy calculations. We identified four hit compounds from the ZINC database that have similar binding poses to RTP while possessing lower overall binding free energies, with ZINC097971592 having a binding free energy two times lower than RTP.

BackgroundNuss procedure is the most common method of surgical treatment to pectus excavatum (PE). A significant percentage of surgeons choose to use thoracoscopic assistance during the Nuss procedure (TNP) to avoid cardiac injury. However, our previous findings confirm the safety of single incision Non-thoracoscopic Nuss Procedure (SINTNP). Hence, Further studies, particularly prospective randomized controlled trials, are necessary to assess the value of SINTNP for PE.MethodsThis study is a prospective, superiority, multicenter, non-masked, randomized controlled trial that investigates the outcome and hospitalization medical expense of SINTNP compared to TNP for PE. A total of 320 eligible patients according to sample size calculation by retrospective data will be randomly assigned to the SINTNP group or the TNP group at a 1:1 ratio using stratified blocked randomization and the zone length was set as four. Patients aged between 3 and 18 years old for the first surgery and without combination of complex anomalies such as Marfan syndrome and congenital heart disease will be considered for the study. The co-primary endpoint is thoracic related complications and medical expense during hospitalization. Thoracic related complications were defined as pneumothorax, pleural effusion, pneumonia and incision infection. The secondary endpoints include surgery duration and length of hospital stay.The registration number for this study protocol is ChiCTR230073081 (Chinese Clinical Trial Registry, A Primary Registry of International Clinical Trial Registry Platform, World Health Organization).

Abstract Background Bladder cancer (BLCA) is one of the most diagnosed cancers in humans worldwide. Recently, immunotherapy has become a main treatment option for BC. However, most BLCA patients do not respond to immune checkpoint inhibitors or relapse after immunotherapy. Therefore, it is very important to identify novel biomarkers for the prediction of immunotherapy response in B patients. Methods Pancancer single‐cell RNA sequencing (scRNA‐seq) data were used to identify the clusters of CD4+ T cells in the tumour microenvironment (TME). The clinical significance of key CD4+ T‐cell clusters was evaluated based on the survival data of two independent immunotherapy bladder cancer (BLCA) cohorts. We also investigated the function of key clusters of CD4+ T cell in the TME of BC cells in vitro. Results This study identified two novel exhausted CD4+ T‐cell subpopulations with the expression of PD1hi CD200hi or PD1hi CD200low in BC patients. Moreover, BLCA patients with a high level of PD1hi CD200hi CD4+ exhausted T cell showed immunotherapy resistance. Cell function analysis demonstrated that PD1hi CD200hi CD4+ exhausted T cell can promote epithelial–mesenchymal transition (EMT) and angiogenesis in BLCA cells. In addition, PD1hi CD200hi CD4+ exhausted T cells were shown to communicate with malignant BLCA cells through the GAS6–AXL axis. Finally, we also found that GAS6 expression is upregulated in B cells by METTL3‐mediated m6A modification. Conclusions PD1hi CD200hi CD4+ exhausted T cell may serve as a novel biomarker for poor prognosis and immunotherapy resistance in B. Targeted inhibitors of PD1hi CD200hi CD4+ exhausted T cells may help improve the efficacy of immunotherapy.

Megakaryocytes (MKs) are the unique non-pathological cells that undergo polyploidization in mammals. The polyploid formation is critical for understanding the MK biology, and transcriptional regulation is involved in the differentiation and maturation of MKs. However, little is known about the functions of transcriptional elongation factors in the MK polyploidization. In this study, we investigated the role of transcription elongation factor EloA in the polyploidy formation during the MK differentiation. We found that EloA was highly expressed in the erythroleukemia cell lines HEL and K562. Knockdown of EloA in HEL cell line was shown to impair the phorbol myristate acetate (PMA) induced polyploidization process, which was used extensively to model megakaryocytic differentiation. Selective over-expression of EloA mutants with Pol II elongation activity partially restored the polyploidization. RNA-sequencing revealed that knockdown of EloA decelerated the transcription of genes enriched in the ERK1/2 cascade pathway. The phosphorylation activity of ERK1/2 decreased upon the EloA inhibition, and the polyploidization process of HEL was hindered when ERK1/2 phosphorylation was inhibited by PD0325901 or SCH772984. This study evidenced a positive role of EloA in HEL polyploidization upon PMA stimulation through enhanced ERK1/2 activity.

BackgroundCoarctation of the aorta (CoA), is a congenital malformation, often combined with several cardiac abnormalities. At present, the operation effect is satisfactory, but postoperative restenosis is still a matter. Identification of risk factors for restenosis and prompt therapy adjustments may improve patient outcomes.Materials and methodsA retrospective clinical study of patients under 12 who had CoA repair in 2012–2021, with a randomized cohort population of 475 patients.ResultsA total of 51 patients (M/F: 30/21) with a mean age of 5.33 (2.00–15.00) months and a median weight of 5.60 (4.20–10.00) kg. The mean follow-up was 8.93 (3.77–19.37) months. Patients were divided into 2 groups: no-restenosis (n-reCoA) (G1, 38 patients) and restenosis (reCoA) (G2, 13 patients). ReCoA was defined as a restenosis requiring interventional or surgery or a pressure gradient >20 mmHg at the repair site as reported by B-ultrasound with the presence of an upper and lower limb blood pressure gradient or growing dysplasia. The overall reCoA incidence was 25% (13/51). In multivariate COX regression, smaller preoperative z-score of the ascending aorta (P = 0.009, HR = 0.68) and transverse aortic arch (P = 0.015, HR = 0.66), arm-leg systolic pressure gradient ≥12.5 mmHg at discharge (P = 0.003, HR = 1.09) were independent risk factors for reCoA.ConclusionThe overall outcome of CoA surgery is successful. Smaller preoperative z-score of the ascending aorta and transverse aortic arch, and an arm-leg systolic pressure gradient ≥12.5 mmHg at discharge increase reCoA risk, and closer follow-up for such patients are required especially within 1 postoperative year.

BackgroundIt is now understood that the effectiveness of checkpoint immunotherapy can be impaired by immunosuppressive tumor-associated macrophages (TAMs). Nonetheless, the impact of different TAM subpopulations on the antitumor immune response remains unclear, mainly due to their heterogeneity. Herein, we identified a novel TAM subpopulation in esophageal squamous cell carcinoma (ESCC) that might contribute to poor clinical outcomes and immunotherapy modulation.Methods and resultsWe analyzed two single-cell RNA sequencing (scRNA-seq) datasets (GSE145370 and GSE160269) of esophageal squamous cell carcinoma to identify a novel TREM2-positive TAM subpopulation characterized by upregulation of TREM2, C1QC, C1QB, C1QA, SPP1, and APOE. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that these genes were significantly overexpressed in ESCC. Multiplex immunofluorescence validated the infiltration of TREM2+ TAMs in ESCC tissues, which correlated with poorer overall survival (OS). The scRNA-seq analysis in dataset GSE120575 indicated significant enrichment of TREM2+ TAMs in melanoma patients (n=48) with poor immunotherapy response, which had an identical gene signature with TREM2+ TAMs from ESCC. Analysis of 29 bulk-RNA melanoma samples from dataset GSE78220 revealed that a gene signature of 40 genes associated with TREM2+ TAMs was upregulated in the transcriptome of melanomas that did not respond to anti-PD1 therapy. Validation in the TCGA ESCC cohort (n=80) showed that a high enrichment score of the TREM2+ TAM was associated with poor prognosis. In addition, 10 ESCC patients treated with anti-PD1 therapy suggested that patients who are not sensitive to immunotherapy have higher density of TREM2+TAMs infiltration.ConclusionOverall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population. modulation; single-cell RNA sequencing

Pulmonary sequestration (PS) is a rare congenital malformation, which mainly contains two variants involving extralobar and intralobar sequestrations. Extralobar sequestrations (ELS) are isolated from the remaining lung tissue and have their visceral pleura. Herein, we report the first case of a torsed ELS associated with congenital lobar emphysema. We described a boy who mainly presented with abdominal and chest pain. A contrast-enhanced computed tomography (CT) scan revealed a mildly enhanced posterior mediastinal mass with left lower lobar emphysema. Thoracoscopic surgery identified a dark and hemorrhagic mass that was connected to the thoracic aorta by a twisted feeding vessel and had its visceral pleura. Pathological findings were consistent with an ELS that had undergone torsion and infarction. The postoperative recovery was uneventful. For the left lower lobar emphysema, he was required for a regular outpatient follow-up. In conclusion, although extremely rare, physicians should maintain a high index of suspicion for torsed ELS when a posterior mediastinal mass with abdominal or chest pain is presented in children.

Abstract Background To explore whether the “WSI Stitcher”, a program we developed for reconstructing virtual large slide through whole slide imaging fragments stitching, can improve the efficiency and consistency of pathologists in evaluating the tumor bed after neoadjuvant treatment of breast cancer compared with the conventional methods through stack splicing of physical slides. Methods This study analyzed the advantages of using software-assisted methods to evaluate the tumor bed after neoadjuvant treatment of breast cancer. This new method is to use “WSI Stitcher” to stitch all the WSI fragments together to reconstruct a virtual large slide and evaluate the tumor bed with the help of the built-in ruler and tumor proportion calculation functions. Results Compared with the conventional method, the evaluation time of the software-assisted method was shortened by 35%(P

Purpose: Current evidence suggests that phosphoserine aminotransferase 1 (PSAT1) is overexpressed in various tumors. Herein, we investigate the significance of PSAT1 in non-small cell lung cancer (NSCLC) and its correlation with immune infiltration. Methods: The expression profile of PSAT1 in NSCLC patients and related clinical information was obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA-NSCLC) databases. In silico and experimental validation were conducted to assess the role of PSAT1 in NSCLC. Gene set enrichment analysis (GSEA) was performed to investigate the disparities in biological functions between groups with high and low PSAT1 expression. Additionally, the biological characteristics and immune cell infiltration were compared between these two groups. We also assessed whether PSAT1 expression could predict the sensitivity of NSCLC patients to immunotherapy using the immunophenotype score (IPS) and an anti-PD-L1 immunotherapy cohort (IMvig-or210). Furthermore, the difference in drug sensitivity between PSAT1-high and PSAT1-low expression cell lines was investigated. Results: Analysis of transcriptional expression profiles using TCGA data revealed overexpression of PSAT1 in NSCLC tissues correlated with poor overall survival (OS). GSEA results showed enrichment of DNA recombination and repair, nucleotide biosynthesis, and the P53 signaling pathway in the PSAT1-high group. Experimental validation demonstrated that the knockdown of PSAT1 suppressed cell proliferation, migration, and invasion of NSCLC. Immune cell infiltration analysis revealed an immune-activated tumor microenvironment in the PSAT1-low group. It was also observed that PSAT1-low cell lines were more likely to benefit from immunotherapy and several chemotherapy drugs. Conclusions: PSAT1 has enormous potential for applications in the prediction of NSCLC patient outcomes and provides the foothold for more precise individualized treatment of this patient population.

Background: The optimal timing of surgery for pectus excavatum (PE) is controversial. A large proportion of children will not undergo surgery before puberty. However, untimely surgery may lead to a decline in the children’s social adaptation and competitiveness because the children have already developed psychological and physiological impairments due to PE at an early age. The study retrospectively compared the academic performance in PE children undergoing the Nuss procedure versus nonsurgical observation. Methods: This retrospective real-world research study included 480 PE patients with definite surgical indications, in whom it was first recommended that they undergo surgery between the ages of 6 and 12 years old. Academic performance was collected at baseline and 6 years later. A generalized linear regression was calculated to screen the factors affecting the performance. A propensity score matching (PSM) analysis was conducted to reduce the potential for confounding factors between surgical and nonsurgical PE patients. Results: Haller index (HI) and pulmonary function were recognized as factors affecting baseline performance according to the generalized linear regression. For PE children with surgical indications, their academic performance significantly declined after 6 years of nonsurgical observation (52.1% ± 17.1% versus 58.3% ± 16.7%, p = 0.042). The academic performance in the surgery group was better than that in the nonsurgery group 6 years after PSM (60.7% ± 17.7% versus 52.1% ± 17.1%, p = 0.008). Conclusions: The severity of PE will affect the academic performance of children. For PE children with definite surgical indications between the ages of 6 and 12 years old, surgical intervention rather than nonsurgical observation is more conducive to the development of children’s academic performance.

BackgroundPrevious studies suggested that tumor size was an independent risk factor of prognosis for hepatocellular carcinoma (HCC). However, the general prognostic analysis did not consider the interaction between variables. The purpose of this study was to investigate whether the effect of tumor size on the prognosis of isolated HCC without vascular invasion varies according to covariates.MethodsPatients were selected from the Surveillance, Epidemiology, and End Results (SEER) database to investigate whether there was an interaction between age and tumor size on the prognosis. Then the trend test and the value of per 1 SD of tumor size were calculated. In addition, the data of Zhejiang Provincial People's Hospital meeting the requirements were selected to verify the obtained conclusions.ResultsMultivariable Cox regression analysis of the database cohort showed that age, gender, tumor size, pathological grade and marital status were independent risk factors for prognosis. Interaction test showed that there was an interaction between age and tumor size (P for interaction 65 years old. This result was confirmed by trend analysis (P for trend 65 years. Therefore, when analyzing the relationship between tumor size and prognosis, stratified analysis should be performed according to age.

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Interactions between ionic liquids and biomolecules are of great interest due to the intrinsic properties of ionic liquids and the flexibility allowed by mixing and matching cations and anions to create unique ionic liquids. A number of ionic liquid–biomolecule studies have focused on interactions with proteins, including industrially relevant enzymes. One of these, laccase from Trametes versicolor, is a naturally derived enzyme used in the breakdown of phenolic compounds in a wide variety of industries, especially useful in breakdown of lignocellulosic materials. Here, a combination of experiments and molecular dynamics (MD) simulations was used to investigate the interactions of ionic liquids with laccase. Enzyme kinetics assays indicated that ionic liquids composed of tetramethylguanidine (TMG) and either serine or threonine caused significant reduction in enzymatic activity, while kinetics was not impacted by TMG-Asp or TMG-Glu ionic liquids. Similarly, intrinsic fluorescence of laccase in the presence of TMG-Ser and TMG-Thr exhibited a shift in spectral properties consistent with structural destabilization, but again TMG-Asp and TMG-Glu had no impact. MD simulations of laccase and ABTS with/without TMG-Ser ionic liquid provided insight into the deactivation mechanism of laccase. The simulations indicated that TMG-Ser disrupts laccase’s electron transfer mechanism.

Objective To investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).Methods Assessing Very Early Rheumatoid arthritis Treatment-2 (AVERT-2; NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman’s correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression).Results Patient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP))

BackgroundContrast and non-contrast echocardiography are crucial for cardiovascular diagnoses and treatments. Correct view classification is a foundational step for the analysis of cardiac structure and function. View classification from all sequences of a patient is laborious and depends heavily on the sonographer’s experience. In addition, the intra-view variability and the inter-view similarity increase the difficulty in identifying critical views in contrast and non-contrast echocardiography. This study aims to develop a deep residual convolutional neural network (CNN) to automatically identify multiple views of contrast and non-contrast echocardiography, including parasternal left ventricular short axis, apical two, three, and four-chamber views.MethodsThe study retrospectively analyzed a cohort of 855 patients who had undergone left ventricular opacification at the Department of Ultrasound Medicine, Wuhan Union Medical College Hospital from 2013 to 2021, including 70.3% men and 29.7% women aged from 41 to 62 (median age, 53). All datasets were preprocessed to remove sensitive information and 10 frames with equivalent intervals were sampled from each of the original videos. The number of frames in the training, validation, and test datasets were, respectively, 19,370, 2,370, and 2,620 from 9 views, corresponding to 688, 84, and 83 patients. We presented the CNN model to classify echocardiographic views with an initial learning rate of 0.001, and a batch size of 4 for 30 epochs. The learning rate was decayed by a factor of 0.9 per epoch.ResultsOn the test dataset, the overall classification accuracy is 99.1 and 99.5% for contrast and non-contrast echocardiographic views. The average precision, recall, specificity, and F1 score are 96.9, 96.9, 100, and 96.9% for the 9 echocardiographic views.ConclusionsThis study highlights the potential of CNN in the view classification of echocardiograms with and without contrast. It shows promise in improving the workflow of clinical analysis of echocardiography.

In this current work, we apply the topological degree and fixed point theorems to investigate the existence, uniqueness, and multiplicity of solutions for a boundary value problem associated with a fractional-order difference equation. Moreover, we provide some appropriate examples to verify our main conclusions.

Abstract Background To examine two different operation timing for treating patients with a total anomalous pulmonary venous connection (TAPVC) who need emergency surgery and to summarize the effects of the two operation strategies. Methods A retrospective review of 54 patients with TAPVC who underwent operations within 72 h of presentation between December 2010 and July 2019 at a single institution was conducted. All patients exhibited respiratory or hemodynamic instability that required mechanical ventilation and inotropic support. Forty-four patients received emergency operations between 24 to 72 h due to stabilization of the patient’s condition. Stable hemodynamics were achieved, and a stable internal milieu was maintained before the operation. These patients comprised the Stable group (SG). Rather than being subjected to efforts to obtain stable hemodynamics and maintain a stable internal milieu, ten patients received emergency operations immediately within 24 h of diagnosis or an emergency operation is performed immediately due to uncorrectable acidosis or progressive cardiovascular collapse. These patients comprised the Unstable group (UG). The hospital course, operative data, and outpatient records were reviewed. Results In SG group, there were 23 exhibited the supracardiac type, 15 exhibited the cardiac type, 4 exhibited the cardiac type, and 2 exhibited the mixed cardiac type,3 patients were premature, the rest was term infant, PDA was the most common comorbidities (28 patients), the next is severe tricuspid valve regurgitation (21 patients). In UG group, there were 3 exhibited the supracardiac type, 4 exhibited the cardiac type, 3 exhibited the cardiac type, and no patient exhibited the mixed cardiac type, only 1 patient was premature, the rest were term infant. PDA (6 patients) and severe tricuspid valve regurgitation (5 patients) were the top two comorbidities. The median weight, median age at surgery, mean cardiopulmonary bypass (CPB) duration and mean aortic cross-clamp (ACC) duration were not significantly different between the two groups. The median postoperation durations of ventilator support were 8.1 ± 4.6 (2–13) days in the SG group and 4.9 ± 2.1 (2–18) days in the UG group, resulting in a significant difference (p = 0.008), the Post-op days in ICU and Days of hospitalization were 8.64 ± 4.04 days and 19.9 ± 4.27 days in the SG group and 5.6 ± 2.01 days and 14.7 ± 1.75 days in the UG group (P = 0.026 and 0.002). There were 12 hospital mortalities (27.3%) in the SG group and 2 hospital mortalities (20%) in the UG group, resulting in no significant difference in mortality (p = 0.636). Postoperative complications, such as low cardiac output and arrhythmia, were not significantly different between the two groups. The survival rates in the UG and SG groups at 5 years were 87.5 and 89.9%, respectively. There was no difference in survival between the two groups at the latest follow-up (SG group 89.9% versus UG group 87.5%, p = 0.8115). Conclusion An emergency operation should be performed immediately without any delay, it can reduce duration of mechanical ventilation and Days of hospitalization without reducing mortality.

BackgroundAcute kidney injury (AKI) commonly occurs after heart transplantation (HTx), but its association with preoperative right ventricular (RV) function remains unknown. Consequently, we aimed to determine the predictive value of preoperative RV function for moderate to severe AKI after HTx.Materials and methodsFrom 1 January 2016 to 31 December 2019, all the consecutive HTx recipients in our center were enrolled and analyzed for the occurrence of postoperative AKI staged by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Conventional RV function parameters, including RV fractional area change (RVFAC) and tricuspid annular plane systolic excursion (TAPSE), were obtained. The primary endpoint was moderate to severe AKI (the KDIGO stage 2 or 3). The secondary endpoints included the impact of AKI on intensive care unit (ICU) mortality, in-hospital mortality, and 1-year mortality.ResultsA total of 273 HTx recipients were included in the study. Postoperative AKI occurred in 209 (77%) patients, including 122 (45%) patients in stage 1 AKI, 49 (18%) patients in stage 2 AKI, and 38 (14%) patients in stage 3 AKI. Patients with higher AKI stage had lower baseline estimated glomerular filtration rate (eGFR), more frequent diabetes, higher right atrial pressure (RAP), longer cardiopulmonary bypass (CPB) duration, more perioperative red blood cell (RBC) transfusions, and worse preoperative RV function. A multivariate logistic regression model incorporating previous diabetes mellitus [odds ratio (OR): 2.21; 95% CI: 1.06–4.61; P = 0.035], baseline eGFR (OR: 0.99; 95% CI: 0.97–0.10; P = 0.037), RAP (OR: 1.05; 95% CI: 1.00–1.10; P = 0.041), perioperative RBC (OR: 1.18; 95% CI: 1.08–1.28; P < 0.001), and TAPSE (OR: 0.84; 95% CI: 0.79–0.91; P < 0.001) was established to diagnose moderate to severe AKI more accurately [the area under the curve (AUC) = 79.8%; Akaike information criterion: 274].ConclusionPreoperative RV function parameters provide additional predicting value over clinical and hemodynamic parameters, which are imperative for risk stratification in patients with HTx at higher risk of AKI.

Alternative splicing (AS) isoforms create numerous proteoforms, expanding the complexity of the genome. Highly similar sequences, incomplete reference databases and the insufficient sequence coverage of mass spectrometry limit the identification of AS proteoforms. Here, we demonstrated full-length translating mRNAs (ribosome nascent-chain complex-bound mRNAs, RNC-mRNAs) sequencing (RNC-seq) strategy to sequence the entire translating mRNA using next-generation sequencing, including short-read and long-read technologies, to construct a protein database containing all translating AS isoforms. Taking the advantage of read length, short-read RNC-seq identified up to 15,289 genes and 15,906 AS isoforms in a single human cell line, much more than the Ribo-seq. The single-molecule long-read RNC-seq supplemented 4,429 annotated AS isoforms that were not identified by short-read datasets, and 4,525 novel AS isoforms that were not included in the public databases. Using such RNC-seq-guided database, we identified 6,766 annotated protein isoforms and 50 novel protein isoforms in mass spectrometry datasets. These results demonstrated the potential of full-length RNC-seq in investigating the proteome of AS isoforms.

Abstract Objectives The occurrence of pulmonary infection after congenital heart disease (CHD) surgery can lead to significant increases in intensive care in cardiac intensive care unit (CICU) retention time, medical expenses, and risk of death risk. We hypothesized that patients with a high risk of pulmonary infection could be screened out as early after surgery. Hence, we developed and validated the first risk prediction model to verify our hypothesis. Methods Patients who underwent CHD surgery from October 2012 to December 2017 in the Children’s Hospital of Chongqing Medical University were included in the development group, while patients who underwent CHD surgery from December 2017 to October 2018 were included in the validation group. The independent risk factors associated with pulmonary infection following CHD surgery were screened using univariable and multivariable logistic regression analyses. The corresponding nomogram prediction model was constructed according to the regression coefficients. Model discrimination was evaluated by the area under the receiver operating characteristic curve (ROC) (AUC), and model calibration was conducted with the Hosmer-Lemeshow test. Results The univariate and multivariate logistic regression analyses identified the following six independent risk factors of pulmonary infection after cardiac surgery: age, weight, preoperative hospital stay, risk-adjusted classification for congenital heart surgery (RACHS)-1 score, cardiopulmonary bypass time and intraoperative blood transfusion. We established an individualized prediction model of pulmonary infection following cardiopulmonary bypass surgery for CHD in children. The model displayed accuracy and reliability and was evaluated by discrimination and calibration analyses. The AUCs for the development and validation groups were 0.900 and 0.908, respectively, and the P-values of the calibration tests were 0.999 and 0.452 respectively. Therefore, the predicted probability of the model was consistent with the actual probability. Conclusions Identified the independent risk factors of pulmonary infection after cardiopulmonary bypass surgery. An individualized prediction model was developed to evaluate the pulmonary infection of patients after surgery. For high-risk patients, after surgery, targeted interventions can reduce the risk of pulmonary infection.

PURPOSEWe aimed to evaluate the feasibility and safety of a modified technique for portal vein recanalization, percutaneous transluminal sharp recanalization (PTSR), when performing transjugular intrahepatic portosystemic shunt (TIPS) for the treatment of chronic portal vein occlusion (CPVO) and portal hypertension.METHODSNine consecutive patients with CPVO and portal hypertension had undergone TIPS and PTSR procedure after failing in conventional percutaneous catheterization from March 2017 to July 2019. Technical success rates, effectiveness, and complications were evaluated. Follow-up of patients’ clinical outcomes and shunt patency were performed periodically. Primary and secondary shunt patency were analyzed by Kaplan-Meier method.RESULTSThe occluded portal veins were successfully recanalized after failing in conventional percutaneous catheterization, and TIPS procedures were completed in all 9 patients. Two patients suffered from procedure-related complications. A portosystemic pressure gradient

Abstract Objectives To summarize and analyze the clinical characteristics of postoperative complications after minimally invasive closure of transthoracic ventricular septal defect, and to explore the risk factors for its occurrence. Methods Retrospectively analyzed the clinical data of 209 patients underwent transthoracic ventricular septal defect closure performed in the Department of Cardiothoracic Surgery, Children’s Hospital of Chongqing Medical University from January 2018 to January 2020, obtained relevant clinical data from the electronic medical record system and summarized their postoperative complications. And used univariate logistics regression and multivariate logistics regression to analyze the risk factors of its occurrence. Results The postoperative hospital stay of 27 patients was longer than 9 days. Residual shunt occurred in 33 patients recently after operation. One patient underwent surgical treatment again because of mechanical hemolysis after the operation. Two patients were re-operated 1 month and 10 months after surgery because of persistent moderate to severe aortic regurgitation. After surgery, 3 patients underwent pericardiocentesis due to a large amount of pericardial effusion, and 2 patients developed a new atrioventricular block after the operation. No other serious adverse events occurred. Multivariate logistic regression analysis showed that the size of VSD defect (OR: 1.494, 95% Cl: 1.108–2.013, P value: 0.008) was related to long postoperative hospitalization. The residual shunt is related to the size of the occluder (OR: 1.452, 95%Cl: 1.164–1.810, P value: 0.001). In the univariate logistics regression analysis, no risk factors related to serious adverse events were found. Conclusions The minimally invasive closure of transthoracic ventricular septal defect is very effective, with no mortality and low incidence of serious adverse events after surgery. The size of the defect is related to the long postoperative hospitalization, and the size of the occluder is related to the residual shunt in the early postoperative period. No risk factors related to the occurrence of serious adverse events after the operation were found.

The fruit of Rosa laevigata Michx. (FR), a traditional Chinese herb utilized for the treatment of a variety diseases, has notably diverse pharmacological activities including hepatoprotective, anti-oxidant, and anti-inflammatory effects. Despite ongoing research on illustrating the underlying anti-inflammatory mechanism of FR, the principal mechanism remained inadequately understood. In this study, we investigated in depth the molecular mechanism of the anti-inflammatory actions of the ethanol extract of FR (EFR) and its potential targets using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro. We showed that EFR effectively ameliorated the overproduction of inflammatory mediators and cytokines, as well as the expression of related genes. It was further demonstrated that LPS-induced activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) were significantly inhibited by pretreatment with EFR, accompanied by a concomitant decrease in the nuclear translocation of the p65 subunit of NF-κB and activator protein 1 (AP-1). In addition, EFR pretreatment potently prevented LPS-induced decreased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Our data also revealed that the activation of AMPK and subsequent inhibition of the mammalian target of the rapamycin (mTOR) signaling pathway was probably responsible for the inhibitory effect of EFR on LPS-induced inflammatory responses, evidenced by reverse changes observed under the condition of AMPK inactivation following co-treatment with the AMPK-specific inhibitor Compound C. Finally, the main components with an anti-inflammatory effect in EFR were identified as madecassic acid, ellagic acid, quinic acid, and procyanidin C1 by LC–MS and testified based on the inhibition of NO production and inflammatory mediator expression. Taken together, our results indicated that EFR was able to ameliorate inflammatory responses via the suppression of MAPKs/NF-κB signaling pathways following AMPK activation, suggesting the therapeutic potential of EFR for inflammatory diseases.

Abstract Background The purpose of our study was to assess the frequency of occult foreign body aspiration (FBA) and to evaluate the diagnostic difficulties and therapeutic methods for these patients. Methods Between May 2000 and May 2020, 3557 patients with the diagnosis of FBA were treated in our department. Thirty-five patients with occult FBA were included in this study. A retrospective analysis of medical records was performed. Results Twenty-three male patients (65.7%) and 12 female patients (34.3%) were hospitalized due to occult FBA. The average age was 3.60 years (range 9 months-12 years). Most of the patients were younger than 3 years old (n = 25, 71.4%). Coughing (n = 35, 100%) and wheezing (n = 18, 51.4%) were the main symptoms and signs. All the patients were found to have a FBA under the fiberoptic bronchoscope. The most common organic foreign bodies were peanuts (n = 10) and the most common inorganic foreign bodies were pen caps (n = 5). The extraction of foreign bodies under rigid bronchoscopy was applied successfully in 34 patients. Only one patient needed a surgical intervention. Conclusions Occult FBA should always be considered in the differential diagnosis of chronic or recurrent respiratory diseases that are poorly explained, even in the absence of a previous history of aspiration.

BackgroundAn updated meta-analysis was performed to explore the clinical outcomes following the sutureless repair in patients with total anomalous pulmonary venous connection (TAPVC) and compare outcomes between the sutureless technique and conventional surgery.MethodsA systematic search of PubMed, Ovid-Embase, and Cochrane Library (CENTRAL) for relevant published studies that reported the clinical outcomes of the sutureless technique in children with TAPVC was performed in February 2022. The publication language was restricted to English.ResultsEleven studies were included involving 771 patients in total. Following the sutureless technique, the incidences of postoperative pulmonary venous obstruction (PVO) and reoperations due to PVO were 3.3% [95% confidence interval (CI), 1.3–5.3%] and 1.8% (95% CI, 0.3–3.3%), respectively. The early and late mortality rates were 3.2% (95% CI, 1.0–5.3%) and 2.5% (95% CI, 0.7–4.3%), respectively. Compared with conventional surgery, the sutureless technique significantly reduced the incidences of postoperative PVO [odds ratio (OR), 0.16; 95% CI, 0.08–0.33; P < 0.00001], reoperations due to PVO (OR, 0.25; 95% CI, 0.10–0.63; P = 0.003), and early mortality (OR, 0.40; 95% CI, 0.21–0.79; P = 0.008). However, no significant difference was found between conventional surgery and the sutureless technique concerning late mortality (OR, 0.63; 95% CI, 0.13–3.00; P = 0.58).ConclusionThe sutureless technique is superior to conventional surgery for the primary repair of TAPVC concerning postoperative PVO, reoperations due to PVO, and early mortality. However, the level of evidence is of low quality. Prospective cohort studies or randomized control trials (RCTs) should be performed to evaluate the effectiveness of sutureless techniques for primary TAPVC repair.

BackgroundRecently, a new automated software (Heart Model) was developed to obtain three-dimensional (3D) left heart chamber volumes. The aim of this study was to verify the feasibility and accuracy of the automated 3D echocardiographic algorithm in heart transplant (HTx) patients. Conventional manual 3D transthoracic echocardiographic (TTE) tracings and cardiac magnetic resonance (CMR) images were used as a reference for comparison.MethodsThis study enrolled 103 healthy HTx patients prospectively. In protocol 1, left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), left atrial max volume (LAVmax), LA minimum volume (LAVmin) and LV ejection fraction (LVEF) were obtained using the automated 3D echocardiography (3DE) and compared with corresponding values obtained through the manual 3DE. In protocol 2, 28 patients’ automated 3DE measurements were compared with CMR reference values. The impacts of contour edit and surgical technique were also tested.ResultsHeart Model was feasible in 97.1% of the data sets. In protocol 1, there was strong correlation between 3DE and manual 3DE for all the parameters (r = 0.77 to 0.96, p

Abstract Background This study sought to investigate the clinical characteristics of congenital diaphragmatic eventration (CDE) and to compare the efficacies of thoracoscopy and traditional open surgery in infants with CDE. Methods We retrospectively analyzed the clinical data of 125 children with CDE (90 boys, 35 girls; median age: 12.2 months, range: 1 h-7 years; body weight: 1.99–28.5 kg, median body weight: 7.87 ± 4.40 kg) admitted to our hospital in the previous 10 years, and we statistically analyzed their clinical manifestations and surgical methods. Results A total of 108 children in this group underwent surgery, of whom 67 underwent open surgery and 41 underwent thoracoscopic diaphragmatic plication. A total of 107 patients recovered well postoperatively, except for 1 patient who died due to respiratory distress after surgery. After 1–9.5 years of follow-up, 107 patients had significantly improved preoperative symptoms. During follow-up, the location of the diaphragm was normal, and no paradoxical movement was observed. Eleven of the 17 children who did not undergo surgical treatment did not have a decrease in diaphragm position after 1–6 years of follow-up. The index data on the operation time, intraoperative blood loss, chest drainage time, postoperative mechanical ventilation time, postoperative hospital stay and postoperative CCU admission time were better in the thoracoscopy group than in the open group. The difference between the two groups was statistically significant (P