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Abstract Background and objectives Methionine adenosyltransferase I/III deficiency used to be considered a relatively benign disease. This study aims to elucidate the clinical characteristics of methionine adenosyltransferase I/III deficiency patients with neurological manifestations. Methods The clinical data, blood amino acids, plasma total homocysteine, gene variants, brain imaging, treatments and outcomes of 15 patients with methionine adenosyltransferase I/III deficiency were retrospectively analyzed. Results Of these 15 patients, 10 demonstrated neurological abnormalities, with delayed language development, learning difficulties or abnormal brain imaging findings. Eleven patients were identified by newborn screening. Patients with demyelination showed significantly higher blood methionine concentrations at baseline (1102 vs. 396 µmol/L), and their blood methionine remained markedly elevated despite a low-methionine diet. Their plasma total homocysteine was normal to moderate elevated. One patient underwent liver transplantation aged 8 years, which reduced his serum methionine concentration to normal. Compound heterozygous and homozygous MAT1A variants were identified from the patients. Among the 21 variants observed, nine have been reported previously, while 12 were novel. Conclusions Methionine adenosyltransferase I/III deficiency is not just a benign disease. Severe persistent hypermethioninemia can cause brain injuries, especially in the white matter. Liver transplantation may be a potential treatment option for refractory methionine adenosyltransferase I/III deficiency.

Abstract Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P

Abstract Background Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. Methods Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children’s Medical Center of Peking University First Hospital from September 2014 to August 2023. Results Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing. Conclusions Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1.

Abstract Dysregulated glycerophospholipid (GP) metabolism in the brain is associated with the progression of neurodegenerative diseases including Alzheimer’s disease (AD). Routine liquid chromatography-mass spectrometry (LC-MS)-based large-scale lipidomic methods often fail to elucidate subtle yet important structural features such as sn-position, hindering the precise interrogation of GP molecules. Leveraging high-resolution demultiplexing (HRdm) ion mobility spectrometry (IMS), we develop a four-dimensional (4D) lipidomic strategy to resolve GP sn-position isomers. We further construct a comprehensive experimental 4D GP database of 498 GPs identified from the mouse brain and an in-depth extended 4D library of 2500 GPs predicted by machine learning, enabling automated profiling of GPs with detailed acyl chain sn-position assignment. Analyzing three mouse brain regions (hippocampus, cerebellum, and cortex), we successfully identify a total of 592 GPs including 130 pairs of sn-position isomers. Further temporal GPs analysis in the three functional brain regions illustrates their metabolic alterations in AD progression.

Background & Aims: The expression of HBsAg from integrated HBV DNA limits the achievement of functional cure for chronic hepatitis B. Thus, characterising the unique expression and secretion of HBsAg derived from integrated HBV DNA is of clinical significance. Methods: A total of 563 treatment-naive patients and 62 functionally cured patients were enrolled, and HBsAg and HBcAg immunohistochemistry of their liver biopsy tissues was conducted followed by semi-quantitative analysis. Then, based on stratified analysis of HBeAg-positive and -negative patients, long-read RNA sequencing analysis, as well as an in vitro HBV integration model, we explored the HBsAg secretion characteristics of integrated HBV DNA and underlying mechanisms. Results: In contrast to the significantly lower serum HBsAg levels, no significant decrease of intrahepatic HBsAg protein was observed in HBeAg-negative patients, as compared with HBeAg-positive patients. The results of long-read RNA sequencing of liver tissues from patients with chronic HBV infection and in vitro studies using integrated HBV DNA mimicking dslDNA plasmid revealed that, the lower HBsAg secretion efficiency seen in HBeAg-negative patients might be attributed to an increased proportion of preS1 mRNA derived from integrated HBV DNA instead of covalently closed circular DNA. The latter resulted in an increased L-HBsAg proportion and impaired HBsAg secretion. Enhancer 1 (EnhI) in integrated HBV DNA could retarget preS1 (SP1) and preS2 (SP2) promoters to disrupt their transcriptional activity balance. Conclusions: The secretion of HBsAg originating from integrated HBV DNA was impaired. Mechanistically, functional deficiency of core promoter leads to retargeting of EnhI and thus uneven activation of the SP1 over the SP2 promoter, resulting in an increase in the proportion of L-HBsAg. Impact and implications: Integrated hepatitis B virus (HBV) DNA can serve as an important reservoir for HBV surface antigen (HBsAg) expression, and this limits the achievement of a functional cure. This study revealed that secretion efficiency is lower for HBsAg derived from integrated HBV DNA than HBsAg derived from covalently closed circular DNA, as determined by the unique sequence features of integrated HBV DNA. This study can broaden our understanding of the role of HBV integration and shed new light on antiviral strategies to facilitate a functional cure. We believe our results are of great general interest to a broad audience, including patients and patient organisations, the medical community, academia, the life science industry and the public.

BackgroundPrevious research has primarily examined the mental well-being of children from labor migrant families, yet there is a lack of understanding regarding the mental well-being of children from highly educated migrant backgrounds. This study investigated the social-emotional problems of 3-5-year-olds from highly educated migrant families residing in an urban area of China, as well as explored potential differences in demographic variables.MethodsA cross-sectional study was conducted in Qiantang District, Hangzhou, China, with 1,494 (53.3% boys) children selected via a convenient sampling method. The Ages & Stages Questionnaires: social-Emotional, Second Edition (ASQ:SE-2) was used to measure social-emotional problems.ResultsThe results showed that 23.6% of the children were at risk for social-emotional problems. More boys (26.7%) than girls (20.1%) had scores above the cut-off. Additionally, more children in the low socioeconomic status (29.9%) had scores above the cut-off than those in the high socioeconomic status (18.9%). There were three common issues among all age groups: “being more active than others,” “excessive attachment to parents,” and “being overly friendly with strangers.ConclusionThe social-emotional development of children from highly educated migrant families is a significant aspect that deserves recognition, contributing valuable insights to the existing literature on this topic.

The pointing and positioning accuracy of precision instruments in aerospace are often disturbed by low-frequency vibrations. An active/passive vibration isolation system is a feasible solution to suppress low-frequency vibrations. However, the vibration isolation performance of the active control strategy is seriously affected by the uncertainty of the system and the difficulty to meet the higher requirements of new-generation equipment. This paper proposes an active composite control (ACC) strategy for vibration isolation systems with uncertainty. The proposed ACC integrates feedforward control based on known systems and feedback control based on the Kalman filter for systems with uncertainty. Further, the derivation and stability analyses of the proposed ACC algorithm are provided, and the influence of system uncertainty on vibration isolation performance based on the proposed ACC is analyzed. Experimental verification is conducted and the experimental results confirm that the proposed ACC can effectively realize the low-frequency and wide-band vibration isolation for the system with uncertainty. Starting from 30 Hz, the vibration isolation performance of the proposed ACC with uncertainty is significantly improved than that of the ACC completely based on a deterministic system model.

Objectives: This systematic review aimed to synthesize the literature on factors influencing the quality of life in living liver donors post-donation and to provide a reference for developing targeted interventions in clinical practice. Methods: A systematic search guided by the PRISMA 2020 approach was performed on specific databases: PubMed, EMBASE, CINHAL with full text, Web of Science, and ProQuest Dissertations & Theses databases. Peer-reviewed articles published in English from inception to October 2022 covering cross-sectional studies and longitudinal studies on factors affecting the quality of life of living liver donors after donation were included in this systematic review. The methodological quality of the studies was examined using a modified version of the National Institutes of Health Quality Assessment Tool. Results: A total of 6,576 studies were retrieved, and 16 eligible studies were finally included. Four types of independent influencing factors: sociodemographic (gender, donor age, education, ethnicity, and marital status), donation-related (length of hospital stay and number of hospitalizations/hospital visits related to donation surgery, recipient outcome, time from donation, complications, donation decision, ambivalence about donating, donor-recipient relationship), health-related (body mass index and pre-donation physical symptoms), and psychosocial (pre-donation physical and mental score, household income, anxiety, depression), were extracted from the included studies. Several studies consistently identified old age, recipient death, recent donation, postoperative complications experienced by donors, and donor concerns about their well-being as negative influencing factors on physical function. Female donors, low education levels, longer hospital stays, and/or more hospital visits due to donation, poor recipient outcome, recent donation, pre-donation concerns regarding their well-being, and first-degree relative and spouse/partner donors were reported in several studies as negative predictors for psychological status. Factors affecting social function were considered by only two included articles. Conclusions: The quality of life of living liver donors could be affected by both donation surgery and psychosocial factors. Based on the above-influencing factors, clinical nurses can develop targeted interventions to improve the quality of life of living liver donors.

Abstract Background Serum cholinesterase (ChE) is positively associated with incident diabetes and dyslipidemia. We aimed to investigate the relationship between ChE and the incidence of diabetic retinopathy (DR). Methods Based on a community-based cohort study followed for 4.6 years, 1133 participants aged 55–70 years with diabetes were analyzed. Fundus photographs were taken for each eye at both baseline and follow-up investigations. The presence and severity of DR were categorized into no DR, mild non-proliferative DR (NPDR), and referable DR (moderate NPDR or worse). Binary and multinomial logistic regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) between ChE and DR. Results Among the 1133 participants, 72 (6.4%) cases of DR occurred. The multivariable binary logistic regression showed that the highest tertile of ChE (≥ 422 U/L) was associated with a 2.01-fold higher risk of incident DR (RR 2.01, 95%CI 1.01-4.00; P for trend

Based on the hydrogeological perspective, the variation in the groundwater level (W) was selected as the analysis factor, and the rainfall changes and groundwater exploitation (QGE) were considered to be the influencing factors. The influence of the two factors on W in the northern Huangqihai Basin was analyzed qualitatively and quantitatively. Results showed that both rainfall and QGE showed increasing trends from 1996 to 2020, while the W values decreased. The correlation between QGE and W was weaker in wet years than in normal years but was the highest in dry years. The mutation time was determined to be 2004. Based on the slope-changing ratio of the cumulative quantity method and the elastic coefficient method, it was determined that the contribution of rainfall changes to W was 22.08% and that of QGE was 77.92%. This study highlights the effectiveness of the integration of qualitative analyses and quantitative evaluation for identifying the influence of external factors on groundwater and well documents that the elastic coefficient method can be used in this field. More attention should be focused on the scientific management of QGE to minimize its negative influence on the sustainable development of groundwater. HIGHLIGHTS Integration of the qualitative analysis and quantitative evaluation provides an effective way to identify the influence of external factors on the groundwater level.; The elastic coefficient method is used in the field of groundwater for the first time, and it is approved to be a simple and effective method to evaluate the contributions of external factors to groundwater.;

Abstract Aim This study aimed to systematically characterize transplant rejection after immune checkpoint inhibitors (ICIs) initiation in solid organ transplant recipients (SOTRs). Methods Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database and case reports in the literature. Disproportionality analysis including information component and reported odds ratio (ROR) was performed to access potential risk signals. Results A total of 168 patients with transplant rejection after ICIs usage were identified in the FAERS database, and 89 cases were identified in the literature review. ICIs were significantly associated with transplant rejection (ROR025: 2.2). A strong risk signal was found for combination therapy with pembrolizumab and ipilimumab compared to monotherapy. Conclusion Immune checkpoint inhibitors were significantly associated with transplant rejection in SOTRs.

Background: Pectus excavatum is not rare in China. Many treatments for this disease have proved to have many shortcomings. Nuss procedure has been a ground-breaking technology, but it also has some disadvantages. Hence, this study was conducted to review our experience in the use of modified Nuss procedure in our hospital. Methods: Data from 259 patients suffered from pectus excavatum between August 2020 and August 2021 who were treated with modified Nuss procedure was analyzed retrospectively. Result: Age was from 3 to 37 years. The average was 15.54 years. The male was 213 cases and the female was 46 cases. The time patients or their family members found pectus excavatum varied. 10 cases had been repaired previously when patients were admitted in our hospital. The clinical symptoms also varied. Each case had an improvement in Haller index. The average of the postoperative hospitalization was 3.97 days. Most cases were inserted 1 bar. Complication rate was also very low. All patients or their parents or their guardians were satisfied with the appearance of the chest wall after operation. There was no death in the whole observation period. Conclusion: From our experience, this modified Nuss procedure have obtained optimistic outcomes with more minimal invasion and low complication rate. This surgical method may be applied to many other hospitals in the future.

A wave of Omicron infections rapidly emerged in China in 2022, but large-scale data concerning the safety profile of vaccines and Coronavirus disease 2019 (COVID-19) infection features in liver transplant (LT) recipients have not been collected. Therefore, the aim of this study was to assess the protectiveness and safety profile of the inactivated vaccines in LT patients against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections. A multi-centre retrospective study was conducted in a cohort with a history of liver transplantation. A total of 1881 participants (487 vaccinated and 1394 unvaccinated patients) were enrolled from seven centres in China. Fourteen of the participants were infected by Omicron, and 50% patients had over 14 days of viral shedding duration. The protection rate of COVID-19 vaccinations to Omicron was 2.59%. The three breakthrough infections occurred more than 6 months after fully vaccinated. A total of 96 (19.7%) vaccinated patients had adverse events, including fatigue, myalgia, liver dysfunction, swelling, and scleroma. There were more Grade 3 adverse events in the preoperative vaccination group than those in the postoperative vaccination group. Inactivated whole-virion SARS-CoV-2 vaccines are safe in patients with post-liver transplantation. The efficacy of inactivated vaccines decreases after 6 months of vaccination, it is recommended that liver transplant patients get boosted vaccinations as early as possible even when they are fully vaccinated. Although clinical manifestations of Omicron infections were mild in LT patients, unvaccinated patients might have a higher risk of liver dysfunction during infections.

Background & Aims: No prospective studies have examined the association between thigh subcutaneous fat distribution and non-alcoholic fatty liver disease (NAFLD). We investigated the associations of thigh subcutaneous fat distribution with incidence and remission of NAFLD in a community-based prospective cohort. Methods: We followed 1,787 subjects, who underwent abdominal ultrasonography, abdominal and femoral magnetic resonance imaging scans, and anthropometric assessments. Associations of thigh subcutaneous fat area/abdominal fat area ratio and thigh circumference/waist circumference ratio with incidence and remission of NAFLD were estimated using the modified Poisson regression model. Results: Over a mean 3.6-year follow-up, 239 incident cases of NAFLD and 207 regressed cases of NAFLD were identified. Increasing thigh subcutaneous fat area/abdominal fat area ratio was associated with a lower risk of incident NAFLD and a higher likelihood of remission of NAFLD [risk ratio (RR) per SD: 0.69, 95% CI 0.59-0.81; 1.20, 95% CI 1.07-1.34, respectively). Each one SD increase in thigh circumference/waist circumference ratio was associated with a 16% lower risk of incident NAFLD (RR 0.84, 95% CI 0.76-0.94) and a 22% higher likelihood of remission of NAFLD (RR 1.22, 95% CI 1.11-1.34). Additionally, the effects of thigh subcutaneous fat area/abdominal fat area ratio on the incidence and remission of NAFLD were mediated through adiponectin (14.9% and 26.6%), homeostasis model assessment of insulin resistance (9.5% and 23.9%), and triglyceride (7.5% and 19.1%). Conclusions: These results demonstrated that a favourable fat distribution, characterised by a greater ratio of thigh subcutaneous fat to abdominal fat, had a protective role against NAFLD. Impact and implications: The associations of thigh subcutaneous fat distribution with NAFLD incidence and remission have not been prospectively examined in a community-based cohort. Our findings suggest that greater thigh subcutaneous fat relative to a given amount of abdominal fat has a protective effect against NAFLD among the middle-aged and older Chinese populations.

Abstract Background Liver cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC). However, some HCC cases can also originate from non-cirrhotic livers. The aim of this study was to identify key circular RNAs (circRNAs) associated with the tumorigenesis of non-cirrhotic liver disease. Methods The differently expressed circRNAs between non-cirrhotic and cirrhotic HCCs were assessed with use of high-throughput circRNAs sequencing and validated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Potential biological functions of these dysregulated circRNAs were predicted with use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-mRNA regulation network was constructed as achieved with use of miRanda software and visualized using Cytoscape software. Biological functions of the four most prominent dysregulated circRNAs identified were confirmed by in vitro experiments. Moreover, possible translations of these dysregulated circRNAs were also predicted. Results A total of 393 dysregulated circRNAs were identified between non-cirrhotic and cirrhotic HCC, including 213 that were significantly up-regulated and 180 significantly down-regulated circRNAs. Expression levels of the six most prominent dysregulated circRNAs were further validated using qRT-PCR. Many tumor related miRNAs were involved in the circRNA-miRNA-mRNA networks, including miR-182-5p, miR-561-3p, miR-125a-5p, miR-145, miR-23b-3p and miR-30e-3p, and downstream mRNAs of dysregulated circRNAs were significantly related with biological processes involved in the progression of tumors, including proliferation, migration, differentiation, and focal adhesion. Results from the in vitro experiments demonstrated that the most prominent dysregulated circRNAs exerted notable effects upon the proliferation and migration of HCC cells. Finally, we also identified 19 dysregulated circRNAs having potential for the coding of functional peptides. Conclusion The results of this present study indicate that circRNAs may play important roles in tumorigenesis of non-cirrhotic HCC. Such findings provide some novel insights and pave the way for the development of future studies directed at investigating the initiation and treatment of HCC.

Abstract Background Acetaminophen (APAP) overdose is a major cause of the morbidity of acute liver failure. The current clinically approved treatment for APAP poisoning, N-acetylcysteine (NAC), has a limited therapeutic window, and prolonged treatment with NAC delays liver regeneration. Mesenchymal stem cells (MSCs) also have therapeutic effects on APAP-induced mouse liver failure, but whether the effects are comparable to those of NAC has not been determined, and the mechanism still needs further exploration. Methods Fasted C57BL/6 mice that received 500 mg/kg APAP were treated intravenously with 300 mg/kg NAC or different amounts of MSCs at 2 h after APAP to investigate survival, hepatocyte necrosis and neutrophil/macrophage recruitment. In vitro co-culture was performed to study the anti-necrotic effects of MSCs on the APAP-injured hepatocyte cell line L-O2. Results MSCs dose-dependently rescued the C57BL/6J mice from APAP-induced liver failure, with 87.5% of MSCs (1 × 106) surviving similar to that of NAC (90%). MSC has similar effects on reduced hepatocyte necrosis and granulocytic myeloid-derived suppressor cells (MDSC) infiltration but enhanced the proportion of regenerative monocytic MDSC when compared to NAC. Mechanistically, MSCs attenuate hepatocyte necrosis by secreting hepatocyte growth factor (HGF). When HGF was knocked down, the protective effects of MSCs were reduced on APAP-induced hepatocyte necrosis and mouse liver failure. Conclusions MSCs are comparable to NAC against APAP-induced liver failure by secreting HGF with less regenerative retardation concerns, thus facilitating the application of MSCs in clinical therapy for APAP liver failure.

Abstract Background The postoperative delirium is a common yet serious complication in elderly patients with hip fracture. We aimed to evaluate the potential risk factors of delirium in patients with hip fracture, to provide reliable evidence to the clinical management of hip fracture. Methods This study was a retrospective design. Elderly patients who underwent hip fracture surgery in our hospital from June 1, 2019 to December 30, 2020 were selected. The characteristics and treatment data of delirium and no delirium patients were collected and compared. Multivariate logistic regression analysis was performed to analyze the influencing factors affecting postoperative delirium in elderly patients with hip fracture. Results A total of 245 patients with hip fracture were included, the incidence of postoperative delirium in patients with hip fracture was 13.06%. There were significant differences in the age, BMI, history of delirium, estimated blood loss and duration of surgery (all p

Abstract. Background:. Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression. Methods:. The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation. Results:. CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2. Conclusion:. CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

Liver fibrosis, which is characterized by the excessive deposition of extracellular matrix (ECM) materials (primarily fibrillar collagen-I), is an abnormal repair reaction and pathological outcome of chronic liver diseases caused by alcohol abuse, non-alcoholic fatty liver disease, and chronic hepatitis B and C virus infections. Liver fibrosis often progresses to liver cirrhosis and hepatocellular carcinoma. Ferroptosis, characterized by lipid peroxidation, is a form of iron-dependent non-apoptotic cell death, and recent studies have reported that ferroptosis contribute to the development of liver fibrosis. Moreover, several agents have demonstrated therapeutic effects in experimental liver fibrosis models by inducing hepatic stellate cell (HSCs) ferroptosis. This review delineates the specific mechanism by which ferroptosis contributes to the development of liver fibrosis. Specifically, we focused on the different types of therapeutic agents that can induce HSCs ferroptosis and summarize their pharmacological effectiveness for liver fibrosis treatment. We suggest that HSCs ferroptosis may be a potential useful target of novel therapies for preventing and treating liver fibrosis.

Diabetic ulcers are the second largest complication caused by diabetes mellitus. A great number of factors, including hyperchromic inflammation, susceptible microbial infection, inferior vascularization, the large accumulation of free radicals, and other poor healing-promoting microenvironments hold back the healing process of chronic diabetic ulcer in clinics. With the increasing clinical cases of diabetic ulcers worldwide, the design and development of advanced wound dressings are urgently required to accelerate the treatment of skin wounds caused by diabetic complications. Electrospinning technology has been recognized as a simple, versatile, and cost-reasonable strategy to fabricate dressing materials composed of nanofibers, which possess excellent extracellular matrix (ECM)-mimicking morphology, structure, and biological functions. The electrospinning-based nanofibrous dressings have been widely demonstrated to promote the adhesion, migration, and proliferation of dermal fibroblasts, and further accelerate the wound healing process compared with some other dressing types like traditional cotton gauze and medical sponges, etc. Moreover, the electrospun nanofibers are commonly harvested in the structure of nonwoven-like mats, which possess small pore sizes but high porosity, resulting in great microbial barrier performance as well as excellent moisture and air permeable properties. They also serve as good carriers to load various bioactive agents and/or even living cells, which further impart the electrospinning-based dressings with predetermined biological functions and even multiple functions to significantly improve the healing outcomes of different chronic skin wounds while dramatically shortening the treatment procedure. All these outstanding characteristics have made electrospun nanofibrous dressings one of the most promising dressing candidates for the treatment of chronic diabetic ulcers. This review starts with a brief introduction to diabetic ulcer and the electrospinning process, and then provides a detailed introduction to recent advances in electrospinning-based strategies for the treatment of diabetic wounds. Importantly, the synergetic application of combining electrospinning with bioactive ingredients and/or cell therapy was highlighted. The review also discussed the advantages of hydrogel dressings by using electrospun nanofibers. At the end of the review, the challenge and prospects of electrospinning-based strategies for the treatment of diabetic wounds are discussed in depth.

Abstract Background Conventional dynamic contrast enhanced (DCE) magnetic resonance (MR) hardly achieves a good imaging performance of arteries and lymph nodes in the breast area. Therefore, a new imaging method is needed for the assessment of breast arteries and lymph nodes. Methods We performed prospective research. The research included 52 patients aged from 25 to 64 between June 2019 and April 2020. The isotropic e-THRIVE sequence scanned in the coronal direction after DCE-THRIVE. Reconstructed images obtained by DCE-THRIVE and the coronal e-THRIVE were compared mainly in terms of the completeness of the lateral thoracic artery, thoracodorsal artery, and lymph nodes. We proposed a criterion for evaluating image quality. According to the criterion, images were assigned a score from 1 to 5 according to the grade from low to high. Two board-certified doctors evaluated images individually, and their average score was taken as the final result. The chi-square test was used to assess the difference. Results The coronal e-THRIVE score is 4.60, which is higher than the DCE-THRIVE score of 3.48, there are significant differences between the images obtained by two sequences (P = 1.2712e−8). According to the score of images, 44 patients (84.61%) had high-quality images on the bilateral breast. Only 3 patients’ (5.77%) images were not ideal on both sides. The improved method is effective for most patients to get better images. Conclusions The proposed coronal e-THRIVE scan can get higher quality reconstruction images than the conventional method to visualize the course of arteries and the distribution of lymph nodes in most patients, which will be helpful for the clinical follow-up treatment.

Abstract The use of organic mulch is important for urban green applications. For urban areas in arid and semiarid regions receiving short high-intensive rainfall, rainfall characteristics, and soil slope play an important role for mulch functioning. These properties of mulch were studied. For this purpose, rainfall simulation experiments using organic mulching were conducted in Jiufeng National Forestry Park to analyze the influence of organic mulch under different slope and heavy rainfall events. The results showed that soil water content displayed a decreasing tendency with increasing mulch application. Compared to bare soil, a mulch application of 0.25 kg/m2 and 0.50 kg/m2 led to maximum soil water content and maximum runoff decrease occurred for 0.50 kg/m2 mulch. Higher application rate of mulch displayed less soil water content and greater runoff. The runoff amount and runoff generation rate decreased by 28–83% and 21–83%, respectively, as compared to bare soil. With a mulch application of 0.25–1.00 kg/m2, soil drainage accounted for 56–60% of total rainfall. Overall, an efficient mulch application was found to be 0.25–0.50 kg/m2. The results of this study are relevant for arid and semiarid urban regions that experience heavy rainfall.

Objective To evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhotic PVT, and compare differences in efficacy and safety among different anticoagulants. Methods We comprehensively searched Pubmed, Cochrane Library, EMBASE, and ClinicalTrials.gov from inception to April 2022 for studies using anticoagulants for cirrhotic PVT. Meta-analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results 3 RCTs and 14 cohort studies involving 1270 patients were included. Anticoagulant therapy can increase the recanalization rate compared with non-anticoagulation therapy (OR 4.44, 95% CI 3.11-6.32, I 2 = 2.5%) and can decrease the extension rate of cirrhotic PVT (OR 0.33, 95% CI 0.18-0.62, I 2 = 41.0%), without increasing the incidence of total bleeding (OR 1.21, 95% CI 0.75-1.97, I 2 = 9.8%), major bleeding (OR 0.98, 95% CI 0.49-1.95, I 2 = 19.7%), and variceal bleeding (OR 0.35, 95% CI 0.12-1.01, I 2 = 39.9%). Subgroup analysis showed that VKA, LMWH, and DOACs could increase the recanalization rate of PVT and were not associated with the risk of bleeding. Studies that compared direct oral anticoagulants (DOACs) with warfarin directly showed that the recanalization rate of PVT in the DOACs group might be higher than that in the warfarin group (OR 30.99, 95% CI 7.39-129.87, I 2 = 0.0%), and there was no difference in the rate of total bleeding (OR 0.30, 95% CI 0.01-8.65, I 2 = 79.6%). Conclusions Anticoagulants are safe and effective in patients with cirrhotic PVT. The rate of PVT recanalization associated with DOACs may be higher than warfarin.

Abstract As one of the most malignant cancer types, hepatocellular carcinoma (HCC) is highly invasive and capable of metastasizing to distant organs. Intermedin (IMD), an endogenous peptide belonging to the calcitonin family, has been suggested playing important roles in cancer cell survival and invasion, including in HCC. However, how IMD affects the behavior of HCC cells and the underlying mechanisms have not been fully elucidated. Here, we show that IMD maintains an important homeostatic state by activating the ERK1/2-EGR1 (early growth response 1) signaling cascade, through which HCC cells acquire a highly invasive ability via significantly enhanced filopodia formation. The inhibition of IMD blocks the phosphorylation of ERK1/2, resulting in EGR1 downregulation and endoplasmic reticulum stress (ER) stress, which is evidenced by the upregulation of ER stress marker DDIT3 (DNA damage-inducible transcript 3). The high level of DDIT3 induces HCC cells into an ER-stress related apoptotic pathway. Along with our previous finding that IMD plays critical roles in the vascular remodeling process that improves tumor blood perfusion, IMD may facilitate the acquisition of increased invasive abilities and a survival benefit by HCC cells, and it is easier for HCC cells to obtain blood supply via the vascular remodeling activities of IMD. According to these results, blockade of IMD activity may have therapeutic potential in the treatment of HCC.

Abstract Highly upregulated in liver cancer (HULC) had a significant predictive effect on tumor growth and metastasis of hepatocellular carcinoma (HCC); however, the mechanisms of HULC on HCC still need to be clarified. We attempted to determine the roles of HULC and miR‐107 in autophagy and invasion of HCC. HULC siRNA reduced the level of autophagy. The impact of HULC siRNA on invasion can be reversed by activating autophagy in HCC cell lines. Further studies on HULC and autophagy were conducted. An interacting sequence between HULC and miR‐107, as well as miR‐107 and Atg12, was predicted by software. The relationship of each pair of molecules was confirmed by luciferase reporter assays. The negative impacts of miR‐107 on autophagy and invasion were proved in HCC cell lines. The inhibitor of miR‐107‐promoted invasion can also be reversed by Atg12 siRNA. The changes of miR‐107, Atg12, epithelial‐mesenchymal transition, and autophagy in transplanted tumors of mouse models also confirmed the results in HCC cell lines. Finally, we find that HULC acts as an endogenous sponge, which abolishes the binding of miR‐107 on the Atg12 3′‐UTR and promotes autophagy and metastasis of HCC.

Abstract Background In this study, we sought to evaluate the feasibility of improved transcatheter aortic valve implantation (TAVI) in noncalcified aortic valve by using the novel concept of double-layer ChenValve prosthesis. TAVI was initially considered as an alternative treatment for high-risk patients with aortic stenosis. However, non noncalcified aortic valve disease was considered as a contraindication to TAVI. Methods ChenValve prosthesis, which consisted of a self-expanding Nitinol ring, a balloon-expandable cobalt-chromium alloy stent and a biological valve, was implanted at the desired position under fluoroscopic guidance in a transapical approach through a 20F sheath in 10 goats. Aortic angiography was performed to measure the diameter of the aotic annulus and assess the performance of the artificial valve. The ultrasound was used to evaluate the regurgitation or paravalvular leakage and trans-prosthetic vascular flow velocity postoperatively. The aortogram and transthoracic echocardiography were applied to observe whether the valve stent was implanted at the desired position. Results ChenValve prosthesis was successfully transppical implanted in all animals. The aortogram and transthoracic echocardiography performed immediately after implantation revealed that the valve stent was implanted at the desired position. There was no significant paravalvular leakage, obstruction of coronary artery ostia, stent malpositioning or dislodgement occurred. Conclusions This preliminary trial with the novel double-layer ChenValve prosthesis demonstrated the feasibility of improved TAVI in noncalcified aortic valve. The mechanism of Nitinol ring-guided locating the aortic sinus enables us to anatomically correct position the artifact valve. This improved strategy seems to make the TAVI process more safe and repeatable in noncalcified aortic valve.

Objectives: Invasive fungal infection (IFI) remains an important cause of mortality in liver transplantation (LT). The objective of this meta-analysis was to identify the risk factors for IFI after LT.Methods: We searched for relevant studies published up to June 2020 from PubMed, Web of Science, Embase, and the Cochrane Library. Odds ratios (ORs) and their corresponding 95% CIs were used to identify significant differences in the risk factors. Heterogeneity between studies was evaluated by the I2 test, and potential publication bias was assessed with Egger's test. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS).Results: A total of 14 studies enrolling 4,284 recipients were included in the meta-analysis. Reoperation (OR = 2.18, 95% CI: 1.61–2.94), posttransplantation dialysis (OR = 2.03, 95% CI: 1.52–2.72), bacterial infection (OR = 1.81, 95% CI: 1.33–2.46), live donor (OR = 1.78, 95% CI: 1.20–2.63), retransplantation (OR = 2.45, 95% CI: 1.54–3.89), and fungal colonization (OR = 2.60, 95% CI: 1.99–3.42) were associated with the risk factors of IFI after LT.Conclusions: Despite some risk factors that have been identified as significant factors for IFI post-LT, which may inform prevention recommendations, rigorous and well-designed studies with adequate sample sizes should be conducted to solve the limitations of this study.

Pneumonia is a common disease in patients. This paper discusses the signal processing techniques of electrocardiogram (ECG) and the statistical analysis of myocardial enzymes in the diagnosis and treatment of patients with pneumonia and analyzes its significance. Detecting the activity of creatine kinase (CK), isoenzyme (CK-MB), and cardiac troponin T (CTnT) before and after treatment in patients with pneumonia and recording the changes of the electrocardiogram with non-invasive bedside conventional electrocardiogram can be useful for medical diagnosis. In addition, in order to eliminate the ECG signal noise to improve the accuracy of analysis and diagnosis, we have introduced a Butterworth filter to achieve the suppression of interference signals. Moreover, the Butterworth filter method is used to denoise the ECG signal, and the selection of wavelet function, the analysis of noise frequency band, and the threshold processing are solved accordingly. This method has the characteristics of simple calculation and fast processing speed. It can effectively suppress baseline drift noise and improve the overall operation speed. The experimental results show that the proposed method can well filter baseline drift, power frequency interference, EMG interference, and other high-frequency interference in ECG signals, and the real-time performance of the Butterworth filter method in the sampling process has good performance, which provides help for diagnosis. Via comparing and analyzing different ECG signal parameters between the groups, the serum levels of CK, CK-MB, and troponin are demonstrated to be significantly increased with the severity of the disease in patients with pneumonia. Abnormal changes in the ECG indicate that the myocardium may be affected after pneumonia in patients. The detection of CK-MB and troponin levels in the serum of patients with pneumonia has very high sensitivity and specificity. Recording electrocardiogram has good intuitive utility. ECG and myocardial enzyme monitoring are of great significance in the diagnosis and treatment of the development of the disease in patients with pneumonia.

Graft derived cell-free DNA was recently reported as a non-invasive biomarker to detect graft damage or rejection after liver transplantation. There are a number of methods for quantification of Gcf-DNA,3 including quantitative-PCR, digital droplet PCR and massively parallel sequencing (next generation sequencing). Here we present the NGS4 data and fragment size distribution of cell-free DNA in the plasma of patients with inborn errors of metabolism who underwent living-related liver transplantation. For more insights please see Analysis of fragment size distribution of cell-free DNA: a potential noninvasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism. [1]. Keywords: Graft derived cell-free DNA, Fragment size, Living-related liver transplantation, Inborn errors of metabolism

As the chains composed of magnetic particles (MPs) move through a channel, the breaking, recomposing, and sticking to the channel wall of the chains may occur, and it is of great importance to reveal the motion regularity of magnetic nanoparticles when they are used as carriers. In this work, experimental visualizations and numerical simulations were carried out to investigate the bending phenomena of different types of chains composed of micro-sized magnetic particles in a channel flow governed by a transversal magnetic field. The experiments focus on the motion of the MP chain, and different types of chains were observed and photographed. In addition, the pose of the chains was investigated based on the lattice Boltzmann method (LBM) by using particles with diameter equal to the thickness of the chain. It is revealed that as the inlet velocity of carrier fluid increases, the bending degree of the chain increases and the regularities well coincide with the LBM simulation results. The shear force on the end particle was taken to evaluate the stability of the chain. In addition, the reorganization process of two short chains was investigated. It is feasible to model the chain composed of micro-sized MPs with large particles so as to predict the motion regularity of the chains efficiently.

Purpose We aimed to generate a capture platform that integrates a deterministic lateral displacement (DLD) microfluidic structure with magnetic-activated cell sorting (MACS) technology for miniaturized, efficient, tumor antigen-independent circulating tumor cell (CTC) separation. Methods The microfluidic structure was based on the theory of DLD and was designed to remove most red blood cells and platelets. Whole Blood CD45 MicroBeads and a MACS separator were then used to remove bead-labeled white blood cells. We established HepG2 human liver cancer cells overexpressing green fluorescent protein by lentiviral transfection to simulate CTCs in blood, and these cells were then used to determine the CTC isolation efficiency of the device. The performance and clinical value of our platform were evaluated by comparison with the Abnova CytoQuest™ CR system in the separating of blood samples from 12 hepatocellular carcinoma patients undergoing liver transplantation in a clinical follow-up experiment. The isolated cells were stained and analyzed by confocal laser scanning microscopy. Results Using our integrated platform at the optimal flow rates for the specimen (60 µl/min) and buffer (100 µl/min per chip), we achieved an CTC yield of 85.1% ± 3.2%. In our follow-up of metastatic patients, CTCs that underwent epithelial–mesenchymal transition were found. These CTCs were missed by the CytoQuest™ CR bulk sorting approach, whereas our platform displayed increased sensitivity to EpCAMlow CTCs. Conclusions Our platform, which integrates microfluidic and MACS technology, is an attractive method for high-efficiency CTC isolation regardless of surface epitopes.

Organelle selective imaging can reveal structural and functional characters of cells undergoing external stimuli, and is considered critical in revealing biological fundamentals, designing targeted delivery system, and screening potential drugs and therapeutics. This paper describes the nucleoli targeting ability of nanoscale carbon dots (including nanodiamond) that are hydrothermally made with controlled surface charges. The surface charges of carbon dots are controlled in the range of -17.9 to -2.84 mV by changing the molar ratio of two precursors, citric acid (CA) and ethylenediamine (EDA). All carbon dots samples show strong fluorescence under wide excitation wavelength, and samples with both negative and positve charges show strong fluorescent contrast from stained nucleoli. The nucleoli selective imaging of live cell has been confirmed with Hoechst staining and nucleoli specific staining (SYTO RNA-select green), and is explained as surface charge heterogeneity on carbon dots. Carbon dots with both negative and positive charges have better ability to penetrate cell and nucleus membranes, and the charge heterogeneity helps carbon dots to bind preferentially to nucleoli, where the electrostatic environment is favored.

Tapered thin-walled structures have been widely used in wind turbine and rotor blade. In this paper, a spectral finite element model is developed to investigate tapered thin-walled beam structures, in which torsion related warping effect is included. First, a set of fully coupled governing equations are derived using Hamilton’s principle to account for axial, bending, and torsion motion. Then, the differential transform method (DTM) is applied to obtain the semianalytical solutions in order to formulate the spectral finite element. Finally, numerical simulations are conducted for tapered thin-walled wind turbine rotor blades and validated by the ANSYS. Modal frequency results agree well with the ANSYS predictions, in which approximate 30,000 shell elements were used. In the SFEM, one single spectral finite element is needed to perform such calculations because the interpolation functions are deduced from the exact semianalytical solutions. Coupled axial-bending-torsion mode shapes are obtained as well. In summary, the proposed spectral finite element model is able to accurately and efficiently to perform the modal analysis for tapered thin-walled rotor blades. These modal frequency and mode shape results are important to carry out design and performance evaluation of the tapered thin-walled structures.