Search

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC., Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis., Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis., Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC., Competing Interests: The authors declare that they have no conflict of interest to declare., (Copyright 2024, Zhao et al.)

Background/aim: Efficient discharge for stroke patients is crucial but challenging. The study aimed to develop early predictive models to explore which patient characteristics and variables significantly influence the discharge planning of patients, based on the data available within 24 h of admission., Design: Prospective observational study., Methods: A prospective cohort was conducted at a university hospital with 523 patients hospitalised for stroke. We built and trained six different machine learning (ML) models, followed by testing and tuning those models to find the best-suited predictor for discharge disposition, dichotomized into home and non-home. To evaluate the accuracy, reliability and interpretability of the best-performing models, we identified and analysed the features that had the greatest impact on the predictions., Results: In total, 523 patients met the inclusion criteria, with a mean age of 61 years. Of the patients with stroke, 30.01% had non-home discharge. Our model predicting non-home discharge achieved an area under the receiver operating characteristic curve of 0.95 and a precision of 0.776. After threshold was moved, the model had a recall of 0.809. Top 10 variables by importance were National Institutes of Health Stroke Scale (NIHSS) score, family income, Barthel index (BI) score, FRAIL score, fall risk, pressure injury risk, feeding method, depression, age and dysphagia., Conclusion: The ML model identified higher NIHSS, BI, and FRAIL, family income, higher fall risk, pressure injury risk, older age, tube feeding, depression and dysphagia as the top 10 strongest risk predictors in identifying patients who required non-home discharge to higher levels of care. Modern ML techniques can support timely and appropriate clinical decision-making., Relevance to Clinical Practice: This study illustrates the characteristics and risk factors of non-home discharge in patients with stroke, potentially contributing to the improvement of the discharge process., Reporting Method: STROBE guidelines., (© 2024 John Wiley & Sons Ltd.)

CuGaTe 2 -based compounds show great promise in the application for high-temperature thermoelectric power generation; however, its wide bandgap feature poses a great challenge for enhancing thermoelectric performance via structural defects modulation and doping the system. Herein, it is discovered that the presence of Ga Cu antisite defects in the CuGaTe 2 compound promotes the formation of Cu vacancies, and vice versa, which tends to form the charge-neutral structure defects combination with one Ga Cu antisite defect and two Cu vacancies. The accumulation of Cu vacancies in the structure of the (Cu 2 Te) x (Ga 2 Te 3 ) 1- x compounds evolves into twins and stacking faults. This in conjunction with Ga Cu antisite defects intensify the point defects phonon scattering, yielding a dramatic reduction on lattice thermal conductivity from 6.95 W m -1 K -1 for the pristine CuGaTe 2 sample to 2.98 W m -1 K -1 for the (Cu 2 Te) 0.45 (Ga 2 Te 3 ) 0.55 sample at room temperature. Furthermore, the high concentration of charge-neutral defects combination narrows the band gap and increases the carrier concentration, leading to an improved power factor of 1.58 mW/mK 2 at 600 K for the (Cu 2 Te) 0.49 (Ga 2 Te 3 ) 0.51 sample, which is 41% higher than for the pristine CuGaTe 2 sample. Consequently, the highest ZT value of 0.82 is achieved at 915 K for Cu 0.015 (Cu 2 Te) 0.48 (Ga 2 Te 3 ) 0.52 , which represents an enhancement of about 22% over that of the pristine CuGaTe 2 compound.

Introduction: Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The clinical manifestations of CD patients are asymptomatic, bleeding and thrombosis. The majority of patient are asymptomatic. However, the single fibrinogen detection method is easy to cause missed diagnosis or misdiagnosis of CD patients. The treatment strategies of CD patients with different clinical manifestations are also different., Methods: Combing the existing experimental diagnosis technology, literature and our research results, a simple and practical CD diagnostic criteria was proposed. And based on the relevant literature and existing treatment guidelines, more comprehensive treatment recommendations are summarized., Results: In this new criteria, combination Clauss method and PT derived method was proposed to detect fibrinogen and its ratio was used to diagnose for CD. Diagnosis also needs to be combined the clinical manifestations, family investigation and genetic testing. According to different clinical manifestation (bleeding, thrombosis or asymptomatic), treatment methods and strategies are different. The treatment of CD patients should consider the patient's personal and family history of bleeding or thrombosis. Treatment of thrombosis and pregnancy may be more challenging. The risk of bleeding and thrombosis should be evaluated and balanced at all times during clinical treatment. These detailed treatment recommendations can provide reference for patients with different clinical manifestations of CD., Conclusions: The new CD diagnosis criteria and comprehensive treatment recommendations can effectively improve the diagnosis and treatment of CD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the vitamin C microbial fermentation system, oxidative stress limits the growth and 2-keto-l-gulonic acid (2-KLG, the precursor of vitamin C) production of Ketogulonicigenium vulgare. Most Bacillus strains, as helper strains, have been reported to release key biomolecules to reduce oxidative stress and promote the growth and 2-KLG production of K. vulgare. To understand the specific mechanism by which the helper strain and K. vulgare interact to reduce oxidative stress, a novel helper strain, Rhodotorula mucilaginosa A8, was used to construct a consortium in the co-culture fermentation system. Based on the activities of the antioxidant enzymes and quantitative polymerase chain reaction (qPCR) analysis, R. mucilaginosa A8 could reduce oxidative stress and increase 2-KLG production in K. vulgare by upregulating antioxidant enzyme activities and related gene-expression levels. In addition, the carotenoids of R. mucilaginosa promoted 2-KLG production in K. vulgare. Coculture of R. mucilaginosa with K. vulgare increased the yield of carotenoids. This study suggested that helper strains with the ability to reduce oxidative stress in K. vulgare would likely act as potential helper strains for facilitating 2-KLG biosynthesis. This work could provide a theoretical basis for the search for potential helper strains for vitamin C microbial fermentation and for the construction of synthetic microbial communities to produce valuable products., (© 2024 Wiley‐VCH GmbH.)

Background: Renal fibrosis contributes to chronic renal failure and a decline in the quality of life. Bushen Huoxue (BSHX) formula is a Traditional Chinese Medicine used to treat chronic renal failure. However, its mechanisms of action remain unclear., Methods and Results: In this study, a rat model of renal fibrosis was constructed by 5/6 nephrectomy in vivo , and histopathological changes were analyzed using hematoxylin-eosin and Masson's trichrome staining. Angiotensin II (Ang II) was used to establish an in vitro renal fibrosis cell model in vitro . Pyroptosis was measured using flow cytometry. Related markers of fibrosis and NOD-like receptor protein 3 (NLRP3) inflammasome activation were measured using western blotting and enzyme-linked immunosorbent assay. Treatment with BSHX (0.25, 0.5, and 1 g/kg) significantly inhibited renal fibrosis and damage in 5/6 nephrectomized rats and simultaneously reduced oxidative stress and NLRP3 inflammasome activation. Similarly, BSHX treatment reduced the levels of hydroxyproline, transforming growth factor-β, matrix metalloproteinase 2, and matrix metalloproteinase 9 and inactivated the Smad2/3 signaling pathway in Ang II-treated HK-2 cells. Our data also showed that treatment with BSHX reduced NLRP3 inflammasome activation and pyroptosis in Ang II-treated HK-2 cells. Moreover, fibrosis and pyroptosis in HK-2 cells induced by NLRP3 overexpression were reduced by treatment with BSHX., Conclusions: BSHX significantly reduced renal fibrosis and pyroptosis, and its mechanism was mainly associated with the inhibition of reactive oxygen species (ROS)/NLRP3-mediated inflammasome activation.

Aims: Primary pigmented nodular adrenocortical disease (PPNAD), as a rare kind of Cushing's syndrome, is frequently misdiagnosed. To get a better understanding of the disease, we analyzed the clinical characteristics and pathogenic variants of PPNAD., Methods: Databases were searched, and the pathogenic variants and clinical manifestations of patients were summarized from the relevant articles., Results: A total of 210 patients in 86 articles were enrolled with a median age of 22 and a female-to-male ratio of 2:1. Sixty-six (31.43%) patients were combined with Carney complex (CNC) and 94.29% were combined with osteoporosis/osteopenia. Among 151 patients who underwent genetic testing, 87.42% (132/151) had pathogenic variants. Six gene mutations ( PRKAR1A , PDE11A , PRKACA , CTNNB1 , PDE8B , and ARMC5 ) were detected in the patients. The most common mutation was PKAR1A, accounting for 79.47% (120/151). There was a significant correlation between PRKAR1A pathogenic variant and spotty skin pigmentation in CNC concurrent with PPNAD ( p < 0.05). Among pregnant patients with PPNAD, those without surgical treatment and with bilateral adrenalectomy suffered from a high-risk perinatal period. However, patients with unilateral adrenalectomy presented a safe perinatal period., Conclusions: For young patients with Cushing's syndrome, especially female patients with spotty skin pigmentation and osteoporosis/osteopenia, PPNAD should be considered. Unilateral adrenal resection may be considered as an option for women with fertility needs. In view of the difficulty of PPNAD diagnosis, genetic testing before surgery might be a reasonable option. Patients with PPNAD with spotty skin pigmentation should consider the PRKAR1A pathogenic variant and pay attention to CNC., Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023416988., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Ding, He, Fu, Li, Feng, Dong and Liao.)

Aims: Rabson-Mendenhall syndrome (RMS) is a rare autosomal, recessive disorder characterized by severe insulin resistance due to mutations in the insulin receptor (INSR) gene. This study aims to analyze the clinical features and gene mutations in RMS, which have not been extensively studied., Methods: PubMed, Embase, the China National Knowledge Infrastructure, and Wanfang were searched for "Rabson-Mendenhall syndrome" or "Black acanthosis hirsutism insulin resistance syndrome.", Results: A total of 42 cases from 33 articles were included. The body mass index ranged from 18.50 to 20.00 kg/m 2 with an average of 16.00 kg/m 2 . There were no overweight (25.00∼29.90 kg/m 2 ) or obese (≥30.00 kg/m 2 ) patients. Acanthosis was present in 29 cases (29/42, 69.05%); growth retardation in 25 cases (25/42, 59.52%); dental anomalies including absence of teeth, crowding, and malocclusion in 23 cases (23/42, 54.76%); and hirsutism in 17 cases (17/42, 40.48%). The average glycosylated hemoglobin was 9.35%, and the average fasting blood-glucose was 8.44 mmol/L; the mean fasting insulin was 349.96 μIU/mL, and the average fasting C-peptide was 6.00 ng/mL. Diabetes was reported in 25 cases (25/33, 75.76%) all of which were diagnosed before 23 years old. All 42 patients had recorded gene mutations, with 22 patients (22/42, 52.38%) having ≥ 2 mutations and 20 cases (20/42, 47.62%) having only 1 mutation. No statistical differences were found in clinical features and laboratory parameters between patients with different mutations., Conclusion: The study indicates that RMS should be considered in young patients with hyperinsulinemia, hyperglycemia with low weight, acanthosis nigricans, growth retardation, dental anomalies, and hirsutism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Stroke patients with dysphagia and family caregivers will experience multiple transitions during the whole process of the disease and various nursing needs will be generated. There is a lack of knowledge about their experiences at different transition stages. Thus, we aimed to explore the transition experiences of patients with post stroke dysphagia and family caregivers from admission to discharge home., Methods: A semi-structured interview based on Meleis's transition theory was used during hospitalization and telephone follow-up interviews were conducted in the first, third, and sixth month after the diagnosis of dysphagia. Interview transcripts were analyzed using the conventional content analysis method., Results: A total of 17 participants enrolled in the first face-to-face interview, 16 participants took part in the first month's telephone follow-up interview, 14 participants in the third month, and 12 participants in the sixth month. The transition experiences of patients with post stroke dysphagia and family caregivers could be summarized into three themes: (1)transition from onset to admission; (2)transition from discharge to other rehabilitation institutions; and (3)transition from discharge to home. Each theme had identified interrelated subthemes., Conclusions: The experiences of patients with post stroke dysphagia and family caregivers during transition are a dynamic process with enormous challenges in each phase. Collaboration with health care professionals, follow-up support after discharge, and available community and social support should be integrated into transitional nursing to help patients facilitate their transition., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 CHEN et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The primary objective was to establish a radiomics model utilizing longitudinal +cross-sectional ultrasound (US) images of lymph nodes (LNs) to predict cervical lymph node metastasis (CLNM) following differentiated thyroid carcinoma (DTC) surgery., Methods: A retrospective collection of 211 LNs from 211 postoperative DTC patients who underwent neck US with suspicious LN fine needle aspiration cytopathology findings at our institution was conducted between June 2021 and April 2023. Conventional US and clinicopathological information of patients were gathered. Based on the pathological results, patients were categorized into CLNM and non-CLNM groups. The database was randomly divided into a training cohort (n = 147) and a test cohort (n = 64) at a 7:3 ratio. The least absolute shrinkage and selection operator algorithm was applied to screen the most relevant radiomic features from the longitudinal + cross-sectional US images, and a radiomics model was constructed. Univariate and multivariate analyses were used to assess US and clinicopathological significance features. Subsequently, a combined model for predicting CLNM was constructed by integrating radiomics, conventional US, and clinicopathological features and presented as a nomogram., Results: The area under the curves (AUCs) of the longitudinal + cross-sectional radiomics models were 0.846 and 0.801 in the training and test sets, respectively, outperforming the single longitudinal and cross-sectional models (p < 0.05). In the testing cohort, the AUC of the combined model in predicting CLNM was 0.901, surpassing that of the single US model (AUC, 0.731) and radiomics model (AUC, 0.801)., Conclusions: The US-based radiomics model exhibits the potential to accurately predict CLNM following DTC surgery, thereby enhancing diagnostic accuracy., (© 2023. The Author(s).)

Background: Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown., Methods: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes., Results: Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], -0.59, 95% CI, -0.73 to -0.45, p < .01) vs (WMD, -0.29, 95% CI, -0.32 to -0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, -5.12, 95% CI, -5.84 to -4.41, p < .01) compared to non-Asians (WMD, -3.64, 95% CI, -4.38 to -2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01)., Conclusions: Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions., Data Sources: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years., Review Methods: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts., Results: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain., Conclusions: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years., Competing Interests: Declaration of conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis., Methods: Restenosis and atherosclerosis rat models of type 2 diabetes (n  =  20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student's t-test and one-way analysis of variance were used for statistical analysis., Results: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitroC/EBPβ overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBPβ knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBPβ hypomethylation. Additionally, Lin28a overexpression reduced C/EBPβ methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells., Conclusion: Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

In engineering practice, layered rock masses often display obvious anisotropy while deforming and failing, and the failure mode directly impacts the engineering construction stability. In this study, the fracture failure load, fracture toughness, crack deflection angle, and failure mode of a layered rock mass under different fracture modes were analyzed by utilizing improved asymmetric semi-circular disc specimens. According to the constitutive model of transversely isotropic materials, the maximum tensile stress (MTS), maximum energy release rate (MERR), and maximum strain energy density (MSED) calculation formulas were modified, and the calculation formulas of the three prediction criteria under anisotropic materials were derived. The calculation results were compared with the experimental results. The results show that the fracture toughness and crack deflection angle were significantly affected by the weak bedding plane. As a result of applying the MTS criterion, the results are closer to the experimental results, providing a solid foundation for engineering deformation, failure, and fracture analyses.

Understanding mass transfer mechanisms is vital for developing new material synthesis and densification technologies. Ion transport, serving both mass and charge transfer, is essential for the rapid preparation of high-performance fast ionic conductor thermoelectric materials like Zn 4 Sb 3 and Cu 2 Q (Q = S, Se). In the case of dual-cation fast ion conductor materials like CuAgSe, exploring the relationship between cation transport becomes pertinent. In this study, copper (Cu) and selenium (Se) undergo a reaction in the presence of an electric field (∼15 A), resulting in the formation of the CuSe compound. Subsequent to this initial reaction, a subsequent thermal environment facilitates the interaction among Cu, CuSe, and Ag 2 Se, culminating in the rapid formation and densification of CuAgSe (with a relative density exceeding 99%) in just 30 s. Evidently, the diffusion of copper ions substantiates a pivotal role in facilitating mass transfer. As a result, CuAg 1+ x Se samples with different silver contents ( x = 0.01, 0.02, 0.03, 0.04 and 0.05) can effectively inhibit cation vacancy, and introduce highly ordered Ag nanotwins to enhance the electrical transport performance. For CuAg 1.04 Se, a peak ZT value of 1.0 can be achieved at 673 K, which is comparable to the literatures. This work will guide the future electric field-assisted rapid mass transfer of materials.

We described an iron(III) and BF 3 ·OEt 2 -promoted oxygen transfer reaction of N -aryl-α,β-unsaturated nitrones to prepare various N , O -difluoroboron β-ketoiminates in good yields ranging from 24% to 87%. Control experiments revealed that the enaminone was the vital intermediate for the formation of N , O -difluoroboron β-ketoiminates, and iron(III) combined with BF 3 ·OEt 2 played as cocatalyst to promote the oxygen transfer reaction through intramolecular cyclization and N-O bond cleavage. More importantly, an estrone-derived N , O -difluoroboron β-ketoiminate was easily prepared in 40% yield from estrone in four steps.

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary In this case, the authors describe the advantage of using concentrated sodium chloride solution in the management of mucosal edema in a patient undergoing POEM. Owing to the chronic acid and food stasis within the dilatated esophagus in patients with achalasia, it is often common to encounter superficial mucosal congestion and esophagitis (reflux and fungal) during endoscopy. All of these mucosal changes are barriers to a safe POEM procedure because of the inherited increased risk of bleeding and mucosal tear during the incision and tunneling portion of the procedure. Patients are advised to take high-dose proton pump inhibitors for at least 2 weeks before the procedure as well as antifungal medication for 1 week before the procedure to improve mucosal healing. Despite all efforts, persistent mucosal edema and esophagitis are often noted before the procedure. As the authors mentioned, concentrated sodium chloride solution has a drying effect on wounds and would lead to decreased mucosal edema. In general, fibroblast cells play a crucial role in the regeneration of damaged mucosal tissue. It has been shown that concentrated sodium chloride solution could also lead to an increased migration of human fibroblast cells and accelerate tissue regrowth and healing of oral ulcers within days. More trials are needed to assess the efficacy of using concentrated sodium chloride solution in the preoperative period before POEM. Tara Keihanian, MD, MPH, Assistant Professor, Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA Mohamed O. Othman, MD, GIE Senior Associate Editor

Introduction: Tirzepatide is a novel hypoglycemic agent for type 2 diabetes mellitus (T2DM). However, the pathophysiology of T2DM in Asians is different from that in non-Asians, and there is no evidence to explain the differences in the efficacy and safety of tirzepatide between different races., Methods: A literature search was conducted in China National Knowledge Infrastructure (CNKI), PubMed, Cochrane Library, Clinical Trials.gov, and Embase databases for clinical studies of tirzepatide for T2DM. The data extraction process was done independently by two authors. All analyses were performed using STATA 14.0 software and Review Manager 5.3 software., Results: A total of 2118 patients with T2DM from 6 studies were involved, with doses of tirzepatide ranging from 5 to 15 mg administered subcutaneously once weekly. The results showed that compared with control/placebo, tirzepatide was more effective in decreasing fasting blood glucose (FBG) in non-Asians than in Asians, and 10 mg rather than 15 mg was the optimal dose to decrease FBG. Similarly, non-Asians were more effective than Asians in improving glycated hemoglobin (HbA1c). Asians were significantly more effective than non-Asians in reducing body weight and ≥ 5% weight loss. In terms of adverse events, the incidence of gastrointestinal adverse events was higher in Asians than in non-Asians at the same dose, while the incidence of metabolic and nutrition disorders was higher in non-Asians than in Asians., Conclusion: Tirzepatide is a novel agent for the treatment of diabetes and has different efficacy in Asians and non-Asians. Asians were more likely to experience weight loss and gastrointestinal adverse events, whereas non-Asians were more likely to have better glycemic control and more metabolic and nutritional disorders., Trial Registration: PROSPERO registration no. CRD42023489588., (© 2024. The Author(s).)

Background: Type 2 diabetes mellitus (T2DM) is a common comorbidity in patients with chronic obstructive pulmonary disease (COPD) and has been associated with an increased risk of mortality in this population., Purpose: This study was designed to investigate the predictive factors of diabetes awareness (DA), including diabetes knowledge (DK), and diabetes care behaviors (DCB) among older people with both COPD and T2DM., Methods: This was a cross-sectional descriptive correlation study. One hundred thirty-three older-age patients with COPD comorbid with T2DM receiving treatment at a chest hospital were enrolled as participants. Both DK and DCB were utilized to measure DA. The Diabetes Knowledge Questionnaire was utilized to measure DK, and the Summary of Diabetes Self-Care Activities was used to evaluate DCB., Results: The average glycated hemoglobin (HbA1c) was 7.68% ( SD = 1.55%), with 74 (55.6%) participants having a level > 7%. The average DA was 46.46% ( SD = 13.34%), the average DK was 53.42% ( SD = 18.91%), and the average DCB was 39.50% ( SD = 16.66%). In terms of demographic variables, age, diabetes education, diabetes shared care, and HbA1c were all significantly associated with DA, DK, and DCB (all p s < .05). The overall variance in DA was significantly explained by diabetes education and HbA1c (all p s < .05). The overall variance in DK was significantly explained by age, diabetes education, and HbA1c. The overall variance in DCB was significantly explained by diabetes education and HbA1c (all p s < .05)., Conclusions/implications for Practice: Our study findings indicate that older adult patients with COPD comorbid with T2DM are at elevated risks of poor glycemic control and low DA. Healthcare professionals should be aware of these issues and develop appropriate DA plans to prevent poor glycemic control in this population. Providing accurate information on diabetes to older adults with COPD comorbid with T2DM is important to improving their DK and promoting better DCB., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

BACKGROUND Hyperparathyroidism is a common issue in patients on long-term hemodialysis, necessitating parathyroidectomy with deep venipuncture. These patients frequently exhibit a heightened incidence of vascular calcification, complicating deep venipuncture and increasing the risk of associated complications. Therefore, a crucial aspect of preoperative assessment in this population involves identifying vascular calcification, with a preference for ultrasound-guided intraplane puncture. Special care is required to prevent blood vessel injuries and postoperative complications such as deep vein thrombosis. CASE REPORT We present the case of a 66-year-old woman with secondary hyperparathyroidism who encountered challenges during an internal jugular vein puncture, leading to subsequent thrombosis. Initial attempts were hindered by calcification of the internal jugular vein's vascular wall, resulting in stratified damage to the vessel's wall. However, the ultrasound-guided in-plane puncture technique successfully allowed the insertion of a central venous catheter without further damage to the vascular wall. On the postoperative fourth day, thrombus formation was observed in the damaged vascular wall from the initial puncture. CONCLUSIONS The ultrasound-guided in-plane puncture technique is advantageous in overcoming the difficulties associated with puncturing through deep vein calcification in patients with secondary hyperparathyroidism. This technique also diminishes the likelihood of complications such as venous thrombosis.

Background: Proximal tubular cells (PTCs) play a critical role in the progression of diabetic kidney disease (DKD). As one of important progenitor markers, CD133 was reported to indicate the regeneration of dedifferentiated PTCs in acute kidney disease. However, its role in chronic DKD is unclear. Therefore, we aimed to investigate the expression patterns and elucidate its functional significance of CD133 in DKD., Methods: Data mining was employed to illustrate the expression and molecular function of CD133 in PTCs in human DKD. Subsequently, rat models representing various stages of DKD progression were established. The expression of CD133 was confirmed in DKD rats, as well as in human PTCs (HK-2 cells) and rat PTCs (NRK-52E cells) exposed to high glucose. The immunofluorescence and flow cytometry techniques were utilized to determine the expression patterns of CD133, utilizing proliferative and injury indicators. After overexpression or knockdown of CD133 in HK-2 cells, the cell proliferation and apoptosis were detected by EdU assay, real-time cell analysis and flow analysis. Additionally, the evaluation of epithelial, progenitor cell, and apoptotic indices was performed through western blot and quantitative RT-PCR analyses., Results: The expression of CD133 was notably elevated in both human and rat PTCs in DKD, and this expression increased as DKD progressed. CD133 was found to be co-expressed with CD24, KIM-1, SOX9, and PCNA, suggesting that CD133+ cells were damaged and associated with proliferation. In terms of functionality, the knockdown of CD133 resulted in a significant reduction in proliferation and an increase in apoptosis in HK-2 cells compared to the high glucose stimulus group. Conversely, the overexpression of CD133 significantly mitigated high glucose-induced cell apoptosis, but had no impact on cellular proliferation. Furthermore, the Nephroseq database provided additional evidence to support the correlation between CD133 expression and the progression of DKD. Analysis of single-cell RNA-sequencing data revealed that CD133+ PTCs potentially play a role in the advancement of DKD through multiple mechanisms, including heat damage, cell microtubule stabilization, cell growth inhibition and tumor necrosis factor-mediated signaling pathway., Conclusion: Our study demonstrates that the upregulation of CD133 is linked to cellular proliferation and protects PTC from apoptosis in DKD and high glucose induced PTC injury. We propose that heightened CD133 expression may facilitate cellular self-protective responses during the initial stages of high glucose exposure. However, its sustained increase is associated with the pathological progression of DKD. In conclusion, CD133 exhibits dual roles in the advancement of DKD, necessitating further investigation., (© 2024. The Author(s).)

Background: Pyroptosis is a critical form of cell death during the development of chronic kidney disease (CKD). Tripartite motif 6 (TRIM6) is an E3-ubiquitin ligase that participates in the progression renal fibrosis (RF). The aim of this study was to investigate the roles of TRIM6 and Glutathione peroxidase 3 (GPX3) in oxidative stress-induced inflammasome activation and pyroptosis in Ang-II treated renal tubular epithelial cells., Methods: To study its role in RF, TRIM6 expression was either reduced or increased in human kidney-2 (HK2) cells using lentivirus, and Ang-II, NAC and BMS-986299 were served as reactive oxygen species (ROS) inducer, ROS scavenger and NLRP3 agonist respectively. Pyroptosis and mitochondrial ROS were measured by flow cytometry. The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were determined using commercial kits, while the levels of IL-1β, IL-18, IL-6, and tumor necrosis factor-α (TNF-α) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Co-immunoprecipitation (Co-IP) assay was used to evaluate the interaction between TRIM6 and GPX3. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to measure mRNA and protein expression, respectively., Results: Treatment with Angiotensin II (Ang II) increased the protein and mRNA levels of TRIM6 in HK2 cells. Ang II also increased mitochondrial ROS production and the malondialdehyde (MDA) level, but decreased the levels of GSH and SOD. In addition, Ang II enhanced HK2 cell pyroptosis, increased the levels of IL-1β, IL-18, IL-6, and TNF-α, and promoted the expression of active IL-1β, NLRP3, caspase-1, and GSDMD-N proteins. These effects were reversed by knockdown of TRIM6 and by treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. BMS-986299, an NLRP3 agonist treatment, did not affect ROS production in HK2 cells exposed to Ang II combined with NAC, but cell pyroptosis and inflammation were aggravated. Moreover, the overexpression of TRIM6 in HK2 cells resulted in similar effects to Ang II. NAC and GPX3 overexpression in HK2 cells could reverse ROS production, inflammation, and pyroptosis induced by TRIM6 overexpression. TRIM6 overexpression decreased the GPX3 protein level by promoting its ubiquitination, without affecting the GPX3 mRNA level. Thus, TRIM6 facilitates GPX3 ubiquitination, contributing to increased ROS levels and pyroptosis in HK2 cells., Conclusions: TRIM6 increases oxidative stress and promotes the pyroptosis of HK2 cells by regulating GPX3 ubiquitination. These findings could contribute to the development of novel drugs for the treatment of RF., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Aim: Achondroplasia is the most common of the skeletal dysplasias that cause fatal and disabling growth and developmental disorders in children, and is caused by a mutation in the fibroblast growth factor receptor, type 3 gene(FGFR3). This study aims to analyse the clinical characteristics and gene mutations of ACH to accurately determine whether a patient has ACH and to raise public awareness of the disease., Methods: The database of Pubmed, Cochrane Library, Wanfang and CNKI were searched with terms of "Achondroplasias" or "Skeleton-Skin-Brain Syndrome" or "Skeleton Skin Brain Syndrome" or "ACH" and "Receptor, Fibroblast Growth Factor, Type 3" or "FGFR3"., Results: Finally, four hundred and sixty-seven patients with different FGFR3 mutations were enrolled. Of the 138 patients with available gender information, 55(55/138, 40%) were female and 83(83/138, 60%) were male. Among the patients with available family history, 47(47/385, 12%) had a family history and 338(338/385, 88%) patients were sporadic. The age of the patients ranged from newborn babies to 36 years old. The mean age of their fathers was 37 ± 7 years (range 31-53 years). Patients came from 12 countries and 2 continents, with the majority being Asian (383/432, 89%), followed by European (49/432, 11%). Short stature with shortened arms and legs was found in 112(112/112) patients, the abnormalities of macrocephaly in 94(94/112) patients, frontal bossing in 89(89/112) patients, genu valgum in 64(64/112) patients and trident hand were found in 51(51/112) patients. The most common mutation was p.Gly380Arg of the FGFR3 gene, which contained two different base changes, c.1138G > A and c.1138G > C. Ten rare pathogenic mutations were found, including c.831A > C, c.1031C > G, c.1043C > G, c.375G > T, c.1133A > G, c.1130T > G, c.833A > G, c.649A > T, c.1180A > T and c.970&#95;971insTCTCCT., Conclusion: ACH was caused by FGFR3 gene mutation, and c.1138G > A was the most common mutation type. This study demonstrates the feasibility of molecular genetic testing for the early detection of ACH in adolescents with short stature, trident hand, frontal bossing, macrocephaly and genu valgum., (© 2024. The Author(s).)

The energy needs of tubular epithelial components, especially proximal tubular epithelial cells (PTECs), are high and they heavily depend on aerobic metabolism. As a result, they are particularly vulnerable to various injuries caused by factors such as ischemia, proteinuria, toxins, and elevated glucose levels. Initial metabolic and phenotypic changes in PTECs after injury are likely an attempt at survival and repair. Nevertheless, in cases of recurrent or prolonged injury, PTECs have the potential to undergo a transition to a secretory state, leading to the generation and discharge of diverse bioactive substances, including transforming growth factor-β, Wnt ligands, hepatocyte growth factor, interleukin (IL)-1β, lactic acid, exosomes, and extracellular vesicles. By promoting fibroblast activation, macrophage recruitment, and endothelial cell loss, these bioactive compounds stimulate communication between epithelial cells and other interstitial cells, ultimately worsening renal damage. This review provides a summary of the latest findings on bioactive compounds that facilitate the communication between these cellular categories, ultimately leading to the advancement of tubulointerstitial fibrosis (TIF)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guo, Cui, Jiao, Yao, Zhao, Tian, Dong and Liao.)

Purpose: Proximal tubular epithelial cell (PTEC) is vulnerable to injury in diabetic kidney disease (DKD) due to high energy expenditure. The injured PTECs-derived profibrotic factors are thought to be driving forces in tubulointerstitial fibrosis (TIF) as they activate surrounding fibroblasts. However, the mechanisms remain unclear., Methods: The diabetes with uninephrectomy (DKD) rats were used to evaluated renal histological changes and the expression of Claudin-2 by immunofluorescence staining. Then, Claudin-2 expression in PTECs were modulated and subsequently determined the proliferation and activation of fibroblasts by building a transwell co-culture system in normal glucose (NG)or high glucose (HG) condition., Results: Decreased expression of Claudin-2 in PTECs accompanied by tight junction disruption and increased interstitial fibrosis, were detected in DKD rats. In vitro, downregulated Claudin-2 in PTECs promoted proliferation and activation of fibroblasts, which coincided with elevated expression of profibrotic connective tissue growth factor (CTGF) in PTECs. Silenced CTGF inhibited the profibrotic of PTECs via Claudin-2 inhibition. Fibroblasts co-cultured with PTECs transitioned more to myofibroblasts and generated extracellular matrix (ECM) significantly in response to high glucose (HG) stimulation whereas overexpression of Claudin-2 in PTECs reversed the above results. Upregulating CTGF disrupted the beneficial anti-fibrosis effects obtained by overexpression of Claudin-2 in HG condition., Conclusion: Our study suggested that Claudin-2 in PTECs, a key mediator of paracellular cation and water transport, promotes the activation and proliferation of surrounding fibroblasts significantly via CTGF in a paracrine manner., Competing Interests: The authors declare no conflict of interest., (© 2024 Guo et al.)

Background: Poorly differentiated thyroid cancer (PDTC) is a special type of thyroid cancer that threatens the life of the patients. Unfortunately, there are no effective treatments for PDTC right now, so it is urgent to search for new efficacious drugs. This experiment was designed to elucidate the effects of selenomethionine (SeMet) on PDTC in vitro and vivo., Methods: A xenograft animal model was used to assay the volume and weight of PDTC. LncRNA NOMMMUT014201 expression was detected by fluorescence in situ hybridization and Real-time quantitative PCR (qRT-PCR). In vitro experiments were carried on in WRO cells. The Cell Counting Kit-8 assay was performed to test the effect of SeMet on the proliferation of cells. And the migration and invasion of WRO cells by the wound-healing assay, Transwell migration and invasion assays. The cell apoptosis was measured by flow cytometry. In addition, genes related to proliferation, migration, invasion and apoptosis were detected through qRT-PCR and Western Blot., Results: SeMet inhibited the proliferation, migration and invasion and promoted the apoptosis of WRO cells in a dose-dependent manner. Then vivo, SeMet significantly suppressed the volume and weight of PDTC. And SeMet downregulated the expressions of Ki67, PCNA, MMP2, MMP9 and BCL2, but upregulated that of BAX and Cleaved-Caspase 3. Moreover, SeMet upregulated the level of LncRNA NOMMMUT014201 both vivo and in vitro. In addition, repression of LncRNA NOMMMUT014201 removed the inhibition effect of SeMet on WRO cell growth significantly (p<0.05). Further investigation showed that LncRNA NOMMMUT014201 downregulated the expression of miR-6963-5p in PDTC cells, but miR-6963-5p inhibited the level of Srprb. In addition, sh-LncRNA NOMMMUT014201 enhanced the proliferation, migration and invasion but inhibited the apoptosis of WRO cells. However, inhibited miR-6963-5p or overexpressed Srprb relieved the effects of sh-LncRNA NOMMMUT014201on WRO cells., Conclusion: Collectively, SeMet inhibits the growth of PDTC in a dose-dependent manner through LncRNA NONMMUT014201/miR-6963-5p/Srprb signal pathway, thus suggesting that SeMet might be a potential drug for PDTC treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The mineralocorticoid receptor plays an important pathophysiological role in cardiorenal diseases by causing inflammation and fibrosis. Mineralocorticoid receptor antagonists (MRAs) are well known in treating cardiovascular disease and diverse nephropathies. However, the first-generation MRA (spironolactone) and the second-generation MRA (eplerenone) remain underutilized because of the risk of inducing severe adverse events. As a selective nonsteroidal MRA, finerenone is safer and more effective and improves cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the effect of finerenone on cardiorenal outcomes in patients of different races and kidney function (estimated glomerular filtration rate) is unclear., Summary: In this review, we summarized the impact of finerenone on patients with CKD and T2DM from randomized controlled trials. The synthesis of published data aims to address the questions pertaining to the cardiorenal benefits of finerenone among various racial groups and different levels of kidney function., Key Message: Finerenone presents racial differences and effects associated with kidney function in CKD and T2DM patients. Due to the limited data for subgroups, it is prudent to approach the conclusion with caution., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Thyroid cancer is one of the most common endocrine neoplasms. Treatment methods include surgical resection, radioactive iodine therapy, inhibition of thyroid-stimulating hormone, and inhibition of kinase-based target therapies. These treatments induced adverse effects. Lithospermum officinale possesses antioxidant, anticancer, burn-healing, and anti-inflammatory activities, and Shikonin is the main ingredient. Antithyroid cancer studies of Shikonin discovered that it inhibited thyroid cancer cell migration and invasion by suppressing the epithelial-mesenchymal transition; induced cell cycle arrest; induced DNA damage and apoptosis by producing excessive reactive oxygen species; upregulated Bax; increased the stability of p53; decreased the expression of Mdm2; downregulated Slug and MMP-2, MMP-9, and MMP-14; repressed the phosphorylation of Erk and Akt; activated the p16/retinoblastoma protein pathway, leading to apoptosis; suppressed the expression of DNMT1; reduced the PTEN gene methylation; increased the expression of PTEN, leading to the inhibition of migration; increased LC3-II to induce autophagy and apoptosis of medullary thyroid carcinoma; and upregulated βII-tubulin in the cell to produce less resistance to cisplatin and paclitaxel, without cross-resistance to other anticancer agents. In vivo studies showed that it is safe in Sprague-Dawley rats, Beagle dogs, and nude mice., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Three undescribed compounds, 1-(4-hydroxyphenyl)-3-((4-hydroxyphenyl)thio) -2-propanone ( I ), 4'-hydroxybenzyl 4-(4''- hydroxybenzyloxy) benzyl thioether ( II ) and 3-(4'-hydroxybenzyl)-6-hydroxy-quinazolinone ( III ) were isolated from the seeds of Sinapis alba L. The structures of all compounds were elucidated based on NMR and MS analysis, along with the comparison with published data. The potential targets of compounds I - III were identified by virtual screening. The potential inhibitory effects of these compounds on protein kinase C theta type were compared by molecular docking. The docking score of compound III was the highest.

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m 2 ) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m 2 ) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were -6.7% (SE 0.7) with mazdutide 3 mg, -10.4% (0.7) with 4.5 mg, -11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from -7.7% to -12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction., (© 2023. The Author(s).)

Objectives: The primary objective of this meta-analysis was to determine whether high-intensity laser therapy (HILT) was effective in improving pain intensity, cervical range of motion (ROM), functional activity, and quality of life (QOL) in individuals with neck pain., Data Sources: PubMed, PEDro, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to March 26, 2022., Study Selection: Randomized controlled trials (RCTs) involving HILT for neck pain were selected., Data Extraction and Data Synthesis: Two raters were independent in data extraction. The methodological quality was evaluated using the PEDro scale, and the level of evidence was assessed using the GRADE system. RevMan5.4 was used for meta-analysis., Results: Eight RCTs were included and their PEDro scores were moderate to high. Compared with placebo, HILT was effective in improving pain intensity (SMD 2.12, 95%CI 1.24 to 3.00; moderate quality evidence), cervical flexion (SMD 1.31, 95%CI 0.27 to 2.35; moderate quality evidence), extension (SMD 1.43, 95%CI 0.24 to 2.63; moderate quality evidence), right lateral flexion (SMD 1.36, 95%CI 0.15 to 2.56; low-quality evidence). There was a trend of better outcome in functional activity after HILT (SMD 1.73, 95%CI -0.05 to 3.54; low quality evidence)., Limitations: There was limited information available on QOL., Conclusion: HILT may be considered as an adjunctive treatment modality for neck pain. There was moderate quality evidence that HILT may improve pain intensity and cervical ROM in individuals with neck pain, but there was low quality evidence that HILT was not effective in improving functional activity., Systematic Review Registration Number: PROSPERO CRD42021254078 CONTRIBUTION OF THE PAPER., Competing Interests: Conflicts of interest All authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Thyroid dysfunction is the most common immune-related adverse event during anti-programmed cell death 1 (anti-PD-1) therapy. In this study, we monitored patients with advanced malignant tumors who received anti-PD-1 therapy to observe the characteristic of anti-PD-1 therapy-induced thyroid dysfunction and its correlation with prognosis., Methods: Patients with advanced carcinoma treated with anti-PD-1 therapy were evaluated for thyroid function at baseline and after treatment initiation from August 2020 to March 2022. Seventy-three patients were finally included in the study., Results: Among these patients, 19 (26.03%) developed thyroid dysfunction after receiving anti-PD-1 therapy. Primary hypothyroidism and thyrotoxicosis were the most common clinical manifestation. Anti-PD-1-induced thyroid dysfunction occurred 63 (26-131) days after administration; thyrotoxicosis appeared earlier than primary hypothyroidism. In Kaplan-Meier survival analysis, the progression-free survival (PFS) of the thyroid dysfunction group was better than that of the no thyroid dysfunction group (227 (95% confidence interval (CI) 50.85-403.15) days vs 164 (95% CI 77.76-250.24) days, p = 0.026). Male patients had better PFS than female patients (213 (95% CI 157.74-268.26) days vs 74 (95% CI 41.23-106.77) days, p = 0.031). In cox proportional hazards regression model, anti-PD-1-induced thyroid dysfunction remained an independent predictor of better PFS (hazard ratio (HR) = 0.339(0.136-0.848), p = 0.021)., Conclusion: Thyroid dysfunction is a common immune-related adverse events in advanced cancer patients treated with anti-PD-1 therapy and predicts a better prognosis., Trial Registration: This study was retrospectively registered with Trial ClinicalTrials.gov (NCT05593744) on October 25, 2022., (© 2023. The Author(s).)

Objective: The relationship between serum selenium levels and papillary thyroid cancer (PTC), especially the pathological features, still remains controversial. We conducted this study to investigate the relationship between serum selenium levels and PTC in a Chinese population., Methods: Cross-sectional data of 284 patients with PTC were collected from the First Affiliated Hospital of Shandong First Medical University. The general clinical characteristics, serum selenium levels, and tumor pathological features were described in PTC. The association between serum selenium levels and pathological features in PTC was analyzed using SPSS 26.0 statistical software., Results: Our results showed that the median serum selenium level was 79.15 μg/L (IQR: 71.00 - 86.98 μg/L) in PTC patients. Serum selenium levels were lower in females than males ( p = 0.035). Serum selenium levels were negatively correlated with the number of lymph node metastases ( p = 0.048). High serum selenium ( OR = 0.397, 95% CI : 0.217 - 0.725) and diastolic blood pressure ( OR = 1.028, 95% CI : 1.005 - 1.051) were related factors for the incidence of bilateral tumors. High serum selenium ( OR = 0.320, 95% CI : 0.166 - 0.617) and diastolic blood pressure ( OR = 1.066, 95% CI : 1.031 - 1.103) were related factors for tumor multifocal incidence., Conclusions: The serum selenium levels of PTC patients in females were lower than males. High serum selenium levels might be a protective factor in PTC patients. Further research is necessary to better understand the influence of selenium on PTC progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ge, Zhao, Yao, Fu, Tian, Shan, Sun, Feng, Dong and Liao.)

Background: The association between the total bilirubin/albumin (B/A) and the all-cause mortality of critically ill patients with acute kidney injury (AKI) remains unclear. This retrospective study aimed to investigate the relationship between B/A ratio and mortality in patients with AKI., Methods: The clinical data of AKI patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database were retrospectively analyzed. Patients were divided into the low and high B/A groups (B/A ≤ 0.25 and B/A > 0.25, respectively). The primary outcome was 28-day all-cause mortality, and the secondary outcomes were 60-day, 1-year and 4-year all-cause mortality. Kaplan-Meier survival curves and Cox proportional risk models were constructed to evaluate the effect of B/A on survival outcomes., Results: The 28-day mortality rates were 18.00% and 25.10% in the low and high B/A groups, respectively (P < 0.001). The Kaplan-Meier analysis showed that patients with higher B/A values had higher all-cause mortality risk (log-rank P < 0.0001). The multivariate Cox proportional risk analysis showed that B/A was an independent risk predictor for death at 28 days, 60 days, 1 year, and 4 years., Conclusion: B/A is an independent risk factor for increased mortality in patients with AKI and may be used as a predictor of clinical outcomes in AKI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are the main causes of restenosis (RS) in diabetic lower extremity arterial disease (LEAD). However, the relevant pathogenic mechanisms are poorly understood., Methods: In this study, we introduced a "two-step injury protocol" rat RS model, which started with the induction of atherosclerosis (AS) and was followed by percutaneous transluminal angioplasty (PTA). Hematoxylin-eosin (HE) staining and immunohistochemistry staining were used to verify the form of RS. Two-step transfection was performed, with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g, to explore the possible mechanism by which Lin28a exerted effects. 5-ethynyl-2΄-deoxyuridine (EdU) and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the expression of Lin28a protein and let-7 family members., Results: Using a combination of in vitro and in vivo experiments, we discovered that let-7c, let-7g, and microRNA98 (miR98) were downstream targets of Lin28a. More importantly, decreased expression of let-7c/let-7g increased Lin28a, leading to further inhibition of let-7c/let-7g. We also found an increased level of let-7d in the RS pathological condition, suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs., Conclusion: These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of VSMCs in RS., (Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: To determine the reliability of shear-wave elastography (SWE)in assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in neutral head posture (NHP) or forward head posture (FHP)., Methods: Sixteen healthy adults (mean age: 21.69 ± 1.01years, 9 females) were included. SWE mode was chosen to measure the nuchal fascia shear modulus and muscle thickness was measured in B-mode. Measurements were collected by two independent investigators on two different days. The intraclass correlation coefficient (ICC) was used to measure the relative reliability, and the standard error of measurement (SEM) were used to measure the absolute reliability., Results: Intra‑rater (ICC = 0.63-0.89) and inter-rater (ICC = 00.54-0.82) reliability for the nuchal fascia shear modulus were moderate to excellent. Intra‑rater (ICC = 00.64-0.96) and inter-rater (ICC = 00.48-0.86) reliability for upper cervical muscles thickness were moderate to excellent. The SEM percentage oscillated from 3.27% to 13.55%. There were significant differences(P < 0.05) between NHP and FHP on nuchal fascia shear modulus, right side splenius capitis muscle thickness and left side semispinalis capitis muscle thickness, but no significant differences(P > 0.05) were observed between the right and left sides. The upper cervical muscles thickness of males was significantly thicker(P < 0.01) than females while no significant differences were observed (P > 0.05) on the nuchal fascia shear modulus., Conclusions: Ultrasound-based SWE may be a reliable tool for assessing the stiffness of the nuchal fascia and the thickness of upper cervical muscles in clinical practice., Registration Number: ChiCTR2200055736., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Aims: Diabetic kidney disease (DKD) is a severe microvascular complication frequently associated with type 1 and type 2 diabetes mellitus. The objective of this work was to evaluate the relevance of PI3K/Akt pathway polymorphisms and DKD susceptibility by a meta-analysis., Methods: Case-control studies related to the relationship between PI3K/Akt pathway polymorphisms and DKD risk were searched from Pubmed, Embase, Cochrane Library, SINOMED, CNKI, and Wanfang databases. Statistical analysis and heterogeneity test were conducted by Review Manager 5.4., Results: Totally, 52 eligible studies were enrolled, including seven single nucleotide polymorphisms (SNPs) for four genes in the PI3K/AKT pathway (GNB3: rs5443; eNOS: rs1799983, rs869109213, rs2070744; IL-6: rs1800795, rs1800796; TNFα: rs1800629). The "M" allele of eNOS rs1799983 was related to the increased risk of DKD under random effects model, especially in Asian population (Overall:M vs. W: I 2  = 75%, OR = 1.29, 95%CI 1.07-1.56; MM + WM vs. WW: I 2  = 75%, OR = 1.50, 95%CI 1.21-1.86). The "M" allele of eNOS rs869109213 was implicated with higher prevalence of DKD under random effects model, especially in Asian population (Overall:M vs. W: I 2  = 63%, OR = 1.43, 95%CI 1.22-1.68; MM + WM vs. WW: I 2  = 50%, OR = 1.36, 95%CI 1.16-1.58; MM vs. WM + WW: I 2  = 59%, OR = 2.20, 95%CI 1.41-3.43). The "M" allele of eNOS rs2070744 was implicated with higher prevalence of DKD under random effects model, especially in Indian population (Overall: M vs. W: I 2  = 47%, OR = 1.35, 95%CI 1.15-1.59; MM + WM vs. WW: I 2  = 45%, OR = 1.32, 95%CI 1.07-1.62; MM vs. WM + WW: I 2  = 65%, OR = 2.29, 95%CI 1.39-3.77). The "M" allele of IL-6 rs1800796 was predominately associated with higher DKD risks under random effects model, especially in Asian population (Overall: M versus W: I 2  = 23%, OR = 1.49, 95%CI 1.21-1.84; MM + WM vs. WW: I 2  = 1%, OR = 1.43, 95%CI 1.15-1.77; MM + WM vs. WW: I 2  = 71%, OR = 2.77, 95%CI 1.09-7.06)., Conclusions: This meta-analysis indicated that polymorphisms in the PI3K/Akt pathway in eNOS rs1799983, rs869109213, rs2070744, and IL-6 rs1800796 were related to the increased risk of DKD., (© 2023 The Authors. IUBMB Life published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)

Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic Reprogramming is a sign of tumor, and as one of the three major substances metabolism, lipid has an obvious impact. Abnormal lipid metabolism is related to the occurrence of various diseases, and the proportion of people with abnormal lipid metabolism is increasing year by year. Lipid metabolism is involved in the occurrence, development, invasion, and metastasis of tumors by regulating various oncogenic signal pathways. The differences in lipid metabolism among different tumors are related to various factors such as tumor origin, regulation of lipid metabolism pathways, and diet. This article reviews the synthesis and regulatory pathways of lipids, as well as the research progress on cholesterol, triglycerides, sphingolipids, lipid related lipid rafts, adipocytes, lipid droplets, and lipid-lowering drugs in relation to tumors and their drug resistance. It also points out the limitations of current research and potential tumor treatment targets and drugs in the lipid metabolism pathway. Research and intervention on lipid metabolism abnormalities may provide new ideas for the treatment and survival prognosis of tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Wang, Cui, Li, Zhao and Liao.)

Objective: To explore the relationship between short-term rapid hypothyroidism and blood lipid levels in patients with differentiated thyroid cancer (DTC)., Methods: Seventy-five DTC patients scheduled to receive radioactive iodine ablation were enrolled. Levels of thyroid hormone and serum lipids were tested at two time points: the euthyroid before thyroidectomy, and the hypothyroid (off thyroxine). Then the collected data were analyzed., Results: Totally 75 DTC patients enrolled, among them, 5o were female (66.67%) and 25 were male (33. 33%), with an average age of 52.24 ± 1.24 years old. The short-term rapid severe hypothyroidism induced by thyroid hormone withdrawal significantly aggravated dyslipidemia, particularly in patients with dyslipidemia before thyroidectomy (All P < 0.01). However, there was no significant differences between blood lipid levels with different thyroid stimulating hormone (TSH) levels. And our study showed significant negative correlations between free triiodothyronine levels and the changes from euthyjroidism to hypothyroidism in total cholesterol (r=-0.31, P =0.03), triglycerides (r=-0.39, P =0.006), high density lipoprotein-cholesterol (HDL-C) (r=-0.29, P =0.042), and significant positive correlations between free thyroxine and the changes of HDL-C (r=-0.32, P =0.027) were identified in females, however, which were not observed in males., Conclusion: Short-term rapids severe hypothyroidism caused by thyroid hormone withdrawal can lead to rapid significant changes in blood lipid levels. It is necessary to pay attention to dyslipidemia and its long-term effects after thyroid hormone withdrawal, especially in patients with dyslipidemia before thyroidectomy., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03006289?term=NCT03006289&draw=2&rank=1, identifier NCT03006289., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yao, Zhao, Liu, Jiang, Guo, Xu, Zhang, Sheng, Wang, Liao and Dong.)

Background: Diabetic kidney disease (DKD) has mainly been considered as a glomerular disease. Our previous study showed that the progression of DKD was highly correlated with the dysfunction of renal proximal tubular cells. Fermented Cordyceps sinensis (CS), a substitute for natural CS, is a prominent herb widely used in China, and has exhibited excellent efficacy on DKD. However, the underlying mechanisms remain poorly understood., Methods: The database analysis was used to identify the main therapeutic targets and pathways of CS involved in DKD treatment. Next, the protective effects of fermented CS on high glucose (HG, 30 mM) induced HK-2 cell injury was validated through cell proliferation and apoptosis assay, including CCK-8, EdU and TUNEL. Finally, quantitative real‑time PCR (qRT-PCR) and western blotting were used to verify key target genes., Results: Our results revealed that 9 main targets (RELA, JNK1, PTEN, VEGFA, EGF, ERK2, CASP3, AKT1, MMP9) were recognized as key therapeutic targets with excellent binding affinity screened by database analysis and molecular docking. The biological processes were identified by Gene Ontology (GO) enrichment, which appeared mainly involved in the positive regulation of cell proliferation as well as the negative regulation of apoptosis. The verification experiments in vitro revealed that fermented CS significantly attenuated the HG-induced cytotoxicity and apoptosis, and promoted the proliferation of HK-2 cells. Moreover, fermented CS significantly downregulated the expressions of Bax, Caspase-3, VEGFA, P-AKT and P-ERK, and upregulated the expression of PTEN compared with that of HG group., Conclusion: Our results demonstrate that the fermented CS has nephroprotective effects significantly, which functions via promoting proliferation and inhibiting apoptosis of renal proximal tubular cells, likely by targeting Caspase-3, Bax, VEGFA and PTEN. Furthermore, AKT and ERK signaling pathway may be the critical mechanisms underlying the efficacy of fermented CS in DKD treatment., (© 2023. The Author(s).)

Background: The second-generation smoking cessation measures for inpatients in our hospital were provided primarily by physicians. Statistics from January to December 2019 showed a negative trend in the number of inpatient smoking cessation services and health education courses provided., Purpose: Purpose: In this study, a comprehensive systematic literature review on the application of smoking cessation interventions was conducted with the goal of helping enhance the inpatient quit rate at the author's hospital., Resolution: The literature on smoking cessation interventions was reviewed, with the findings used to formulate a feasible plan for the implementation of an effective related intervention at our hospital. During the implementation process, the challenges encountered led to the formulation of strategies, including: 'conducting second-generation smoking cessation on-the-job training,' 'revising the referral process for patients taking smoking-cessation medications,' and 'adding patients who do not cease smoking to the referral process.' Data on the number of individuals attempting to quit smoking and the success rate of smoking cessation were collected. The baseline values before project implementation were compared with the values at 12 and 24-months posttest., Results: The number of individuals receiving smoking cessation services increased from 85 people within 12 months to 105 people, and further increased to 125 people by the 24th month. Comparing the 3-month abstinence rates for 2019 and 2020, an increase from 31.36% before project implementation to 42.67% after implementation was observed, indicating a rise of 11.31%. Also, comparing the 6-month abstinence rates between 2019 and 2020, an increase from 27.16% before project implementation to 42.67% after implementation was observed, indicating a rise of 15.51%. The project outcomes calculated in December 2021 show a three-month abstinence rate of 44.40% and a six-month abstinence rate of 41.82%., Conclusions: The nursing interventions for smoking cessation in this project increased the abstinence rate among inpatients. Evidence-based practices, including earching for quality research evidence, utilizing the 7A framework to bridge evidence and clinical differences, and promoting the project using a collaborative cross-team approach, were the main factors contributing to the success of the project. The evidence-based application of smoking cessation strategies highlights the significant role played by nurses in enhancing the quality of care. The findings may serve as a reference for the future development of nursing project solutions.

Context: Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). Circular RNAs (circRNAs) act as key regulators of DR development by regulating inflammation and angiogenesis. Objective: This study aimed to elucidate the function and mechanism of hsa&#95;circ&#95;0000047 in DR. Materials and methods: High glucose (HG) was used to induce human retinal microvascular endothelial cells (hRMECs) to construct a DR model in vitro. Qualitative real-time polymerase chain reaction (qRT-PCR) or western blotting were used to detected the levels of hsa&#95;circ&#95;0000047, miR-6720-5p, and CYB5R2 in DR and HG-indeced hRMECs. Cell functional experiments were performed to detect the change of viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Besides, the correlation between miR-6720-5p and hsa&#95;circ&#95;0000047/CYB5R2 was confirmed by luciferase assay and Pearson correlation analysis. Results: hsa&#95;circ&#95;0000047 and CYB5R2 were downregulated in DR, whereas miR-6720-5p was upregulated in DR. Cell functional experiments showed that hsa&#95;circ&#95;0000047 overexpression restrained viability, inflammation, migration, invasion, and angiogenesis of HG-induced hRMECs. Regarding mechanism, hsa&#95;circ&#95;0000047 could sponge miR-6720-5p to regulate CYB5R2 expression in hRMECs. Additionally, CYB5R2 knockdown reversed the effects of hsa&#95;circ&#95;0000047 overexpression on HG-induced hRMECs. Conclusion: Our study revealed that hsa&#95;circ&#95;0000047 alleviated inflammation and angiogenesis in HG-induced hRMECs by targeting the miR-6720-5p/CYB5R2 axis, which may be a novel biomarker for DR therapy.

Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves' orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto's thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Li, Li, Cui, Zhao and Liao.)

Aim: To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy., Materials and Methods: This multicentre phase 3 trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once-daily placebo, janagliflozin 25 or 50 mg. After the 24-week treatment period, patients on placebo were re-randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28-week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24., Results: At week 24, the placebo-adjusted least squares mean changes of HbA1c were -0.58% and -0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, and improvements in high-density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28-week extension period. No severe hypoglycaemia occurred throughout the whole 52-week treatment., Conclusions: Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy., (© 2022 John Wiley & Sons Ltd.)

Aims: Resistance to thyroid hormone (RTH) and pituitary tumors are both rare diseases, and the differential diagnosis of these two diseases is difficult in some cases. There are also patients who have both conditions, making diagnosis more difficult. To better understand this aspect, we analyzed the clinical characteristics and gene mutations of RTH coexisting with pituitary tumors., Methods: Database retrieval was conducted in the PubMed, Cochrane Library, and SinoMed databases, and the search contents were case reports or case series of patients with RTH coexisting with pituitary tumors. The demographic, clinical manifestations, and imaging characteristics of pituitary tumors and gene mutations were summarized., Results: Thirteen articles involving 16 patients with RTH coexistent with pituitary tumors, consisting of 13 female patients, one male patient, and two patients with unknown sex, were included. The patients were 10 to 79 years old and most patients were 41-55 years old (43.75%). The 16 patients were from seven different countries and three continents (Asia, the Americas, and Europe). All the patients showed an abnormal secretion of TSH, and five patients underwent transsphenoidal surgery. Finally, four patients were pathologically confirmed to have TSHoma. A total of 11 different mutations occurred at nine amino acid sequence sites (251, 310, 344, 347, 383, 429, 435, 438, and 453). Two different mutations occurred in both the no. 435 and no. 453 amino acid sequences. Fourteen patients provided their treatment histories, and all had undergone different treatment regimens., Conclusions: Patients with both RTH and pituitary tumors had multiple clinical manifestations and different thyroid functions, imaging characteristics of pituitary tumors, genetic mutations of THRβ , and treatments. However, due to the limited number of cases, the patients were mainly women. Further studies with more cases that focus on the mechanism are still needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Xu, Li, Wang, Liao and Dong.)

The pathogenic mechanism of diabetic kidney disease (DKD) is involved in various functions; however, its inadequate characterisation limits the availability of effective treatments. Tubular damage is closely correlated with renal function and is thought to be the main contributor to the injury observed in early DKD. Programed cell death (PCD) occurs during the biological development of the living body. Accumulating evidence has clarified the fundamental role of abnormalities in tubular PCD during DKD pathogenesis. Among PCD types, classical apoptosis, autophagic cell death, and pyroptosis are the most studied and will be the focus of this review. Our review aims to elucidate the current knowledge of the mechanism of DKD and the potential therapeutic potential of drugs targeting tubular PCD pathways in DKD., (© 2022 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background and Aims: The genetic and clinical characteristics of patients with distal renal tubular acidosis (dRTA) caused by SLC4A1 mutations have not been systematically recorded before. Here, we summarized the SLC4A1 mutations and clinical characteristics associated with dRTA., Methods: Database was searched, and the mutations and clinical manifestations of patients were summarized from the relevant articles., Results: Fifty-three eligible articles involving 169 patients were included and 41 mutations were identified totally. Fifteen mutations involving 100 patients were autosomal dominant inheritance, 21 mutations involving 61 patients were autosomal recessive inheritance. Nephrocalcinosis or kidney stones were found in 72.27%, impairment in renal function in 14.29%, developmental disorders in 61.16%, hematological abnormalities in 33.88%, and muscle weakness in 13.45% of patients. The age of onset was younger ( P  < 0.01), urine pH was higher ( P  < 0.01), and serum potassium was lower ( P  < 0.001) in recessive patients than patients with dominant SLC4A1 mutations. Autosomal recessive inheritance was more often found in Asian patients ( P  < 0.05)., Conclusions: The children present with metabolic acidosis with high urinary pH, accompanying hypokalemia, hyperchloremia, nephrocalcinosis, growth retardation and hematological abnormalities should be suspected as dRTA and suggested a genetic testing. The patients with recessive dRTA are generally more severely affected than that with dominant SLC4A1 mutations. Autosomal recessive inheritance was more often found in Asian patients, and more attentions should be paid to the Asian patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Yang, Sheng, Ge, Song, Dong, Guo and Liao.)

Background: Although the prognosis of papillary thyroid carcinoma (PTC) is relatively good, it causes around 41,000 deaths per year, which is likely related to recurrence and metastasis. Lymph node metastasis (LNM) is an important indicator of PTC recurrence and transmembrane 4 superfamily (TM4SF) proteins regulate metastasis by modulating cell adhesion, migration, tissue differentiation, and tumor invasion. However, the diagnostic and prognostic values of TM4SF in PTC remain unclear. Methods: This study aimed to identify TM4SF genes with predictive value for LNM and prognostic value in PTC using bioinformatic analysis. We screened the differentially expressed genes (DEGs) of the TM4SF family in PTC using data from TCGA, constructed a PPI network using STRING, and evaluated the predictive role of TM4SF1 in LNM via a binary logistic regression analysis and ROC curve. We assessed the association between TM4SF1 expression and DNA methylation, and determined the functional and mechanistic role of TM4SF1 in promoting LNM via GSEA, KEGG, and GO. We estimated the relationship between each TM4SF gene and overall survival (OS, estimated by Kaplan-Meier analysis) in patients with PTC and established a predictive model of prognostic indicators using a LASSO penalized Cox analysis to identify hub genes. Finally, we explored the correlation between TM4SFs and TMB/MSI. Results: We identified 21 DEGs from the 41 TM4SFs between N0 (without LNM) and N1 (with LNM) patients, with TM4SF1 , TM4SF4 , UPK1B , and CD151 being highly expressed in the N1 group; several DEGs were observed in the TNM, T, and N cancer stages. The "integrins and other cell-surface receptors" pathway was the most significantly enriched functional category related to LNM and TM4SFs. TM4SF1 was identified as an indicator of LNM (AUC= 0.702). High levels of TM4SF1 might be related to Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT) process in PTC. The higher expression of TM4SF1 was also related to DNA promoter hypomethylation. CD9 , TM4SF4 , TSPAN2 , and TSPAN16 were associated with OS in PTC patients and TSPAN2 has great potential to become a prognostic marker of PTC progression. For the prognostic model, the riskscore = (-0.0058)*CD82+(-0.4994)*+(0.1584)*TSPAN11+(1.7597)*TSPAN19+(0.2694)*TSPAN2 (lambda.min = 0.0149). The AUCs for 3-year, 5-year, and 10-year OS were 0.81, 0.851, and 0.804. TSPAN18 , TSPAN31 , and TSPAN32 were associated with both TMB and MSI in PTC patients. Conclusion: Our findings identified TM4SF1 as a potential diagnostic marker of LNM and TSPAN2 as a prognostic factor for patients with PTC. Our study provides a novel strategy to assess prognosis and predict effective treatments in PTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Li, Zhao, Yao, Lu, Dong, Bai and Liao.)