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Traditional observational studies have reported a positive association between constipation and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between constipation and CRC is scarce. In the study, 2-sample Mendelian randomization analysis was conducted to investigate the potential causal relationship between constipation and CRC. Analysis of the results showed that there was no causal association between constipation and CRC, either in European populations (CRC: odds ratio [OR] = 1.00, 95% confidence interval [CI] = 0.99-1.00, P = .49; rectal cancer: OR = 0.99, 95% CI = 0.99-1.00, P = .79) or in Asian populations (CRC: OR = 1.00, 95% CI = 0.99-1.01, P = .30). Also there was no inverse causal association between CRC and constipation, either in European populations (CRC: OR = 0.10, 95% CI = 2.76E-03-3.45, P = .20; rectal cancer: OR = 0.05, 95% CI = 9.14E-07-2.64E + 03, P = .59) or in Asian population (CRC: OR = 1.18, 95% CI = 0.92-1.52, P = .20), there was no horizontal diversity in the instrumental variables in the Mendelian randomization analyses of the present study (all F statistics >10), and no heterogeneity was found in the regression analyses. The findings from bidirectional 2-sample Mendelian randomization analyses indicate that there is no evidence of a bidirectional causal association between constipation and CRC. However, further investigation is warranted through additional clinical studies and trials to thoroughly explore the association between these 2 factors., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cystic Echinococcosis (CE) is a zoonotic disease causing fibrosis and necrosis of diseased livers caused by infection with Echinococcus granulosus (E.g). There is evidence that E.g is susceptible to immune escape and tolerance when host expression of immunoinflammation and fibrosis is suppressed, accelerating the progression of CE. Ghrelin has the effect of suppressing immunoinflammation and fibrosis, and whether it is involved in regulating the progression of E.g-infected liver lesions is not clear., Methods: Serum and hepatic Ghrelin levels were observed in E.g-infected mice (4, 12 and 36 weeks) and compared with healthy control groups. Co-localization analysis is performed between protein expression of Ghrelin in and around the hepatic lesions of E.g-infected 12-week mice and protein expression of different hepatic histiocytes by mIHC. HepG2 cells and protoscoleces (PSCs) protein were co-cultured in vitro, as well as PSCs were alone in vitro, followed by exogenously administered of Ghrelin and its receptor blocker, [D-Lys3]-GHRP-6, to assess their regulatory effects on immunoinflammation, fibrosis and survival rate of PSCs., Results: Serum Ghrelin levels were increased in E.g-infected 4- and 12-week mice, and reduced in 36-week mice. E.g-infected mice consistently recruited Ghrelin in and around the hepatic lesions, which was extremely strongly co-localized with the protein expression of hepatic stellate cells (HSCs), T cells and the TGF-β1/Smad3 pathway. The secretion of Ghrelin was increased with increasing concentrations of PSCs protein in HepG2 cells culture medium. Moreover, Ghrelin could significantly inhibit the secretion of IL-2, INF-γ and TNF-α, as well as the expression of Myd88/NF-κB and TGF-β1/Smad3 pathway protein, and promoted the secretion of IL-4 and IL-10. Blocking Ghrelin receptor could significantly inhibit PSCs growth in in vitro experiment., Conclusion: Ghrelin is highly expressed in the early stages of hepatic E.g infection and may be involved in regulating the progression of liver lesions by suppression immunoinflammation and fibrosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu 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.)

Tumorous bone defects present significant challenges for surgical bio-reconstruction due to the dual pathological conditions of residual tumor presence and extensive bone loss following excision surgery. To address this challenge, a "thermal switch" smart bone scaffold based on the silicene nanosheet-modified decalcified bone matrix (SNS@DBM) is developed by leveraging the natural affinity between collagen and silicene, which is elucidated by molecular dynamics simulations. Benefitting from its exceptional photothermal ability, biodegradability, and bioactivity, the SNS@DBM "thermal switch" provides an integrated postoperative sequential thermotherapy for tumorous bone loss by exerting three levels of photothermal stimulation (i.e., strong, moderate, and nonstimulation). During the different phases of postoperative bioconstruction, the SNS@DBM scaffold realizes simultaneous residual tumor ablation, tumor recurrence prevention, and bone tissue regeneration. These biological effects are verified in the tumor-bearing nude mice of patient-derived tissue xenografts and critical cranium defect rats. Mechanism research prompts moderate heat stimulus generated by and coordinating with SNSs can upregulate osteogenic genes, promote macrophages M2 polarization, and intensify angiogenesis of H-type vessels. This study introduces a versatile approach to the management of tumorous bone defects., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Artificial bacterial flagella (ABF), also known as a magnetic helical microswimmer, has demonstrated enormous potential in various future biomedical applications (e.g., targeted drug delivery and minimally invasive surgery). Nevertheless, when used for in vivo / in vitro treatment applications, it is essential to achieve the high motion efficiency of the microswimmers for rapid therapy. In this paper, inspired by microorganisms, the surface microstructure was introduced into ABFs to investigate its effect on the swimming behavior. It was confirmed that compared with smooth counterparts, the ABF with surface microstructure reveals a smaller forward velocity below the step-out frequency (i.e., the frequency corresponding to the maximum velocity) but a larger maximum forward velocity and higher step-out frequency. A hydrodynamic model of microstructured ABF is employed to reveal the underlying movement mechanism, demonstrating that the interfacial slippage and the interaction between the fluid and the microstructure are essential to the swimming behavior. Furthermore, the effect of surface wettability and solid fraction of microstructure on the swimming performance of ABFs was investigated experimentally and analytically, which further reveals the influence of surface microstructure on the movement mechanism. The results present an effective approach for designing fast microrobots for in vivo / in vitro biomedical applications.

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus ( E. granulosus ), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body's innate immune defenses and compromise the liver's ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis.

Background: The challenge of emerging antimicrobial resistance and variation in antibiotic use across provinces in China call for knowledge on antibiotic utilization at the regional level. This study aims to evaluate the long-term trends and patterns of antibiotic usage in Xinjiang Province, the largest provincial-level division located in the northwest of China, aiming to provide evidence in enhancing provincial antimicrobial stewardship (AMS) and developing policy measures to optimize regional antimicrobial use., Methods: This was an ecological study with temporal trend analysis on inpatient antibiotic utilization, with antibiotic use data from 92 public hospitals covered by Xinjiang's Center for Antibacterial Surveillance from 2012 to 2022. Antibiotic use was measured by the number of daily defined doses per 100 patient days (DDDs/100 pds). Patterns of antibiotic use were described by Anatomical Therapeutic Chemical (ATC) subgroups and the Access, Watch, Reserve (AWaRe) classification. The Average Annual Percent Change (AAPC) of antibiotic use and the corresponding 95% confidence intervals (CIs) were calculated to describe the trend of antibiotic use over time. Joinpoint regression was performed using the Weighted Bayesian Information Criteria (WBIC) model with a parametric method. A pairwise comparison between secondary and tertiary hospitals was conducted to explore disparities in antibiotic use across hospital levels. The most commonly used antibiotics were also analyzed., Results: The total inpatient antibiotic use in Xinjiang was 27.6 DDDs/100 patient days in 2022, with a significant decreasing trend during 2012-2022 (AAPC, -2.0%; 95% CI, -3.6% to -0.4%). The Watch group antibiotics were the most used AWaRe category, with the Access-to-Watch ratio decreasing significantly from 46.4% to 24.4% (AAPC, -6.8%; 95% CI, -8.4% to -5.1%). No significant difference was found in the trend of total antibiotic use between secondary and tertiary hospitals, but there were disparities across hospital levels in subgroups. Third-generation cephalosporins, second-generation cephalosporins, and fluoroquinolones remained the top three antibiotic class throughout the study period. The number of antibiotics accounting for 90% of the total antibiotic use decreased from 34 antibiotics in 2012 to 18 antibiotics in 2022., Conclusions: The decreasing trend of inpatient antibiotic use in Xinjiang's public hospitals reflects the effects of continuous AMS implementation. Patterns of antibiotic use underscore the need for further efforts on evidence-based antibiotic selection and for analyses on the appropriateness of antibiotic use.

Introduction: The production of bone-like structural scaffolds through bone tissue engineering technology is a promising method for bone regeneration to repair bone defects. Deer antler, an easily harvested and abundantly sourced initial bone tissue structure, resembles the composition and structure of human cancellous bone and can serve as a new material for allogeneic bone transplantation. Methods: This study involved the preparation and characterization of antler powder/chitosan/β-glycerophosphate sodium/polyvinyl alcohol (AP/CS/β-GP/PVA) porous hydrogel scaffolds to verify their material properties and osteogenic mechanisms. The microstructure, hydrophilicity, and mechanical properties of the scaffolds were studied using Scanning Electron Microscopy (SEM), contact angle measurement, and a universal material testing machine. The interactions between the various components were investigated using Fourier-Transform Infrared Spectroscopy (FTIR). Biocompatibility, osteogenic properties, and expression of osteogenesis-related proteins of the scaffolds were evaluated through Cell Counting Kit-8 (CCK-8) assays, alkaline phosphatase staining, Alizarin Red staining, live/dead cell staining, and Western blot analysis. Results: The results showed that as the content of deer antler powder increased, both the hydrophilicity and mechanical properties of the scaffold materials improved, while the porosity slightly decreased with an increase in deer antler powder content. Cell culture experiments demonstrated that scaffolds with a higher proportion of deer antler powder were beneficial for the proliferation and differentiation of mouse pre-osteoblast (MC3T3-E1) cells, with the scaffolds containing 10% and 8% deer antler powder showing the best effects. The upregulation of RUNX2, OCN, OSX, and OPN protein expression may promote differentiation. Discussion: Therefore, the AP/CS/β-GP/PVA hydrogel scaffolds have the potential to become a promising biomaterial for bone tissue engineering., 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 Abudukelimu, Aierken, Tuerxuntayi, Yilihamu, Abulizi, Wufuer and Dong.)

Background: Many related factors can accelerate the age-dependent telomere shortening, but some problems remain unresolved. This study aimed to assess the risk factors of telomere attrition at different age stages., Methods: This study was a population-based nationally representative survey study. All data were collected using a standard methodology by the national surveillance system. Quantitative polymerase chain reaction was used to measure relative leukocyte telomere length. Multiple linear regression analysis with age stratification was used to estimate the association of shortened telomere length with risk factors at the different age stages. Covariance analysis was used to compare the telomere length of category variables, and the model was adjusted for potentially confounders., Results: A total of 7,659 eligible participants aged 20 years or older with DNA specimens participated in the study. Related risk factors for age-dependent telomere shortening included gender, race-ethnicity, education levels, family income, health insurance, marital status, physical activity, smoking status, alcohol use, and self-reported greatest weight, which were associated with change in telomere length at different age stages., Conclusions and Implications: Related risk factors of telomere attrition were changed with age in life course. The evaluation of related risk factors for telomere attrition in terms of age may be a more accurate evaluation comparison with the specific age., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Supraglottic squamous cell carcinoma (SGSCC) is characterized by low differentiation, rapid growth, and inconspicuous initial manifestations. Early detection and prompt treatment can significantly improve survival rates. The main focus of treatment is to maintain optimal laryngeal function., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we conducted univariate and multivariate Cox regression analyses to identify independent prognostic factors for T1-T2 SGSCC. We also enrolled 109 patients with T1-T2 SGSCC from the First Affiliated Hospital of Xinjiang Medical University as an external validation set. In addition, we developed a nomogram to predict the prognosis of T1-T2 SGSCC, assessed the predictive accuracy and discriminatory ability of the nomogram using the area under the curve (AUC), C-index, receiver operating characteristic (ROC) curve and calibration curve, and confirmed the clinical validity of the nomogram using decision curve analysis (DCA)., Results: Our investigation identified nine prognostic indicators for T1-T2 SGSCC: age (≥ 65 years), marital status, American Joint Committee on Cancer (AJCC) stage (II-IV), grade (III-IV), M stage (M1), radiotherapy, chemotherapy, sex (female), and surgery. These variables were used to create accurate nomograms that predict overall and specific survival rates at 1, 3, and 5 years. The nomograms demonstrated superior prognostic value and accuracy compared to AJCC staging. Laryngectomy with partial laryngectomy is the preferred treatment option for T1-T2 SGSCC cases, providing superior overall survival (OS) and cancer-specific survival (CSS). Radiotherapy also improves OS and CSS. Our results were based on a comprehensive analysis of various indicators, including the C-index, ROC curve, calibration curve, and DCA curve., Conclusion: Nomograms provide significant advantages in treatment decision making and diagnosis. Laryngectomy with partial laryngectomy is the most appropriate method for T1-T2 SGSCC cases. However, radiotherapy can also be used. Thus, patients with T1-T2 SGSCC should be evaluated to determine if combination therapy is the optimal treatment approach. Nevertheless, further research is needed to understand the role of chemotherapy. Overall, this study identified nine key predictors of future outcomes, aiding healthcare professionals in assessing risks and making treatment decisions for T1-T2 SGSCC patients., (© 2024. The Author(s).)

Background: Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them., Methods: This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated., Results: When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899-0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796-0.995) and 0.870 (95% CI, 0.769-0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model., Conclusions: DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo ., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Large bony Bankart injuries are typically stabilized using screws or plates or multiple anchors. Here, the "door-locking" technique, using a single-row anchor, can provide effective fixation for massive bony Bankart injuries. This technique offers several advantages over open fixation surgery or other techniques that use more than 2 suture anchors, including simpler surgical procedures, lower medical costs, and satisfactory clinical outcomes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This work involving data collection, data analysis, and editing of the manuscript was supported by the National Key 10.13039/100006190Research and Development Project (2021YFA1201404), Major Project of 10.13039/501100001809NSFC (81991514), Nanjing Drum Tower Hospital 10.13039/501100009584Clinical Research Foundation (2022-LCYJ-MS-21). All authors (Y.Z., J.Q., Q.L., A.A., R.X. D.C., Q.J.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (© 2024 Published by Elsevier Inc. on behalf of the Arthroscopy Association of North America.)

Ulcerative colitis (UC) is a relapsing and reoccurring inflammatory bowel disease. The treatment effect of Alhagi maurorum and stem cell extracts on UC remains unclear. The aim of the present study was to investigate the protective role of Alhagi maurorum combined with stem cell extract on the intestinal mucosal barrier in an intestinal inflammation mouse model. Sixty mice were randomly divided into a control group, model group, Alhagi group, MSC group, and MSC/Alhagi group. MSC and Alhagi extract were found to reduce the disease activity index (DAI) scores in mice with colitis, alleviate weight loss, improve intestinal inflammation in mice ( p < 0.05), preserve the integrity of the ileal wall and increase the number of goblet cells and mucin in colon tissues. Little inflammatory cell infiltration was observed in the Alhagi, MSC, or MSC/Alhagi groups, and the degree of inflammation was significantly alleviated compared with that in the model group. The distribution of PCNA and TNF-alpha in the colonic tissues of the model group was more disperse than that in the normal group ( p < 0.05), and the fluorescence intensity was lower. After MSC/Alhagi intervention, PCNA and TNF-alpha were distributed along the cellular membrane in the MSC/Alhagi group ( p < 0.05). Compared with that in the normal control group, the intensity was slightly reduced, but it was still stronger than that in the model group. In conclusion, MSC/Alhagi can alleviate inflammatory reactions in mouse colonic tissue, possibly by strengthening the protective effect of the intestinal mucosal barrier.

Significant advances in chemotherapy drugs have reduced mortality in patients with malignant tumors. However, chemotherapy-related cardiotoxicity increases the morbidity and mortality of patients, and has become the second leading cause of death after tumor recurrence, which has received more and more attention in recent years. Arrhythmia is one of the common types of chemotherapy-induced cardiotoxicity, and has become a new risk related to chemotherapy treatment, which seriously affects the therapeutic outcome in patients. Traditional Chinese medicine has experienced thousands of years of clinical practice in China, and has accumulated a wealth of medical theories and treatment formulas, which has unique advantages in the prevention and treatment of malignant diseases. Traditional Chinese medicine may reduce the arrhythmic toxicity caused by chemotherapy without affecting the anti-cancer effect. This paper mainly discussed the types and pathogenesis of secondary chemotherapeutic drug-induced arrhythmia (CDIA), and summarized the studies on Chinese medicine compounds, Chinese medicine Combination Formula and Chinese medicine injection that may be beneficial in intervention with secondary CDIA including atrial fibrillation, ventricular arrhythmia and sinus bradycardia, in order to provide reference for clinical prevention and treatment of chemotherapy-induced arrhythmias., 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 Li, Cheng, Zhu, Hu, Wang, Niu, Li, Aierken, Li, Feng and Liu.)

Alzheimer's disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aβ is a typical AD hall marker, but Aβ-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aβ-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aβ-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors.)

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare. Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn's disease (CD)] and DD using the Mendelian randomization (MR) analysis. Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy. Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98-1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94-1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92-1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method. Conclusion: This study's findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies., 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 Aierken, Atabieke, Aierken, Li, Xia, Aizezi and Li.)

Background: Although previous studies found that frailty is prevalent in NAFLD patients with advanced liver fibrosis and cirrhosis, studies examining the relationship are spare., Aim: Our study aspires to investigate the potential correlation between the Frailty Index (FI) and hepatic fibrosis among middle-aged and older adults with NAFLD., Methods: Data from the 2017-2020.03 National Health and Nutrition Examination Survey (NHANES) were utilized for this study, with a final of 2,383 participants aged 50 years and older included. The quantification of frailty was executed employing a 49-item frailty index. The recognition of hepatic steatosis and fibrosis was accomplished through the utilization of the controlling attenuation parameter (CAP) and transient elastography (TE). The relationship between the FI and hepatic fibrosis were investigated employing univariable and multivariable-adjusted logistic regression analyses. A subgroup analysis was conducted, dividing the subjects based on gender, Body Mass Index (BMI), and the presence of hyperlipidemia., Results: The findings demonstrated a positive correlation between the FI and significant hepatic fibrosis in NAFLD, even after using multivariate logistic regression models adjusting for potential confounding factors (OR = 1.022, 95% CI, 1.004-1.041) and in tertiles (Q3vs Q1: OR = 2.004, 95% CI, 1.162-3.455). In the subgroup analysis, the correlation was more statistically significant in male (OR = 1.046, 95% CI, 1.022-1.071), under/normal weight (OR = 1.077, 95% CI, 1.009-1.150), overweight (OR = 1.040, 95% CI, 1.010-1.071), and subjects without hyperlipidemia (OR = 1.054, 95% CI, 1.012-1.097). The area under the Receiver Operating Characteristic (ROC) curve for the FI in assessing the existence of substantial fibrosis in NAFLD was 0.612 (95% CI, 0.596-0.628)., Conclusion: This study demonstrated a positive correlation between significant hepatic fibrosis and frailty, particularly among males aged 50 years and older, who were non-obese and did not have hyperlipidemia with NAFLD. Additional studies are required to further validate these findings., 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 Atabieke, Li, Aierken, Li, Zhang, Aizezi, Gao and Zhang.)

The transcription factor promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16) is critical for the self-renewal of spermatogonial stem cells (SSCs). However, the function of PLZF in SSCs is not clear. Here, we found that PLZF acted as an epigenetic regulator of stem cell maintenance and self-renewal of germ cells. The PLZF protein interacts with the ten-eleven translocation 1 (TET1) protein and subsequently acts as a modulator to regulate the expression of self-renewal-related genes. Furthermore, Transcription Factor 7-like 2 (TCF7L2) is promoted by the coordination of PLZF and Tri-methylation of lysine 4 on histone H3 (H3K4me3). In addition, testicular single-cell sequencing indicated that TCF7L2 is commonly expressed in the PLZF cluster. We demonstrated that PLZF directly targets TCF7L2 and alters the landscape of histone methylation in the SSCs nucleus. Meanwhile, the RD domain and Zn finger domain of PLZF synergize with H3K4me3 and directly upregulate TCF7L2 expression at the transcriptional level. Additionally, we identified a new association between PLZF and the histone methyltransferase EZH2 at the genomic level. Our study identified a new association between PLZF and H3K4me3, established the novel PLZF&TET1-H3K4me3-TCF7L2 axis at the genomic level which regulates undifferentiated spermatogonia, and provided a platform for studying germ cell development in male domestic animals., Competing Interests: Declaration of competing interest All authors read and approved the final manuscript and declare no competing financial interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

III-V/Si multi-junction solar cells have been widely studied in recent years due to their excellent theoretical efficiency (∼42%). In order to solve the problem of lattice mismatch between Si and III-V compounds of III-V/Si solar cells, different hexagonal Si 1- x Ge x buffer layer models on the surface of hexagonal diamond Si(001) were built, and the structural, electronic and optical properties of the proposed models were calculated based on first principles calculations. The results showed that all models of the designed buffer layer could effectively reduce the lattice mismatch, and the buffer layer hex-Si 1- x Ge x ( x = 0, 0.75, and 1) is the ideal model and has achieved the best lattice-matching improvement with high defect formation energy, as well as direct band gap properties and a larger light adsorption coefficient. These theoretical models, with their analyzed properties, could offer a promising pathway toward realizing high efficiency and low cost III-V/Si multi-junction solar cells.

Background: Fractional exhaled nitric oxide (FeNO) measured at multiple exhalation flow rates can be used as a biomarker to differentiate central and peripheral airway inflammation. However, the role of alveolar nitric oxide (CaNO) indicating peripheral airway inflammation remains unclear in gastroesophageal reflux-associated cough (GERC)., Objectives: We aimed to characterize the changes in alveolar nitric oxide (CaNO) and determine its clinical implication in GERC., Design: This is a single-center prospective observational study., Methods: FeNOs at exhalation flow rates of 50 and 200 ml/s were measured in 102 patients with GERC and 134 patients with other causes of chronic cough (non-GERC). CaNO was calculated based on a two-compartment model and the factors associated with CaNO were analyzed. The effect of anti-reflux therapy on CaNO was examined in 26 GERC patients with elevated CaNO., Results: CaNO was significantly elevated in GERC compared with that in non-GERC (4.6 ± 4.4 ppb versus 2.8 ± 2.3 ppb, p  < 0.001). GERC patients with high CaNO (>5 ppb) had more proximal reflux events (24 ± 15 versus 9 ± 9 episodes, p  = 0.001) and a higher level of pepsin (984.8 ± 492.5 versus 634.5 ± 626.4 pg/ml, p  = 0.002) in sputum supernatant than those with normal CaNO. More GERC patients with high CaNO required intensified anti-reflux therapy (χ 2  = 3.963, p  = 0.046), as predicted by a sensitivity of 41.7% and specificity of 83.3%. Cough relief paralleled a significant improvement in CaNO (8.3 ± 3.0 versus 4.8 ± 2.6 ppb, p  < 0.001)., Conclusion: Peripheral airway inflammation can be assessed by CaNO measurement in GERC. High CaNO indicates potential micro-aspiration and may predict a necessity for intensified anti-reflux therapy.

Background: When specific nutrients are inadequate, vulnerability to cardiovascular and metabolic illnesses increases. The data linking dietary nutrition with these illnesses, however, has been sparse in the past observational research and randomized controlled trials., Objectives: A Mendelian randomization (MR) analysis was performed to assess the influence of macronutrients (fat, protein, sugar, and carbohydrates) and micronutrients (β-carotene, folate, calcium, iron, copper, magnesium, phosphorus, selenium, zinc, vitamin C, vitamin D, vitamin B, and vitamin B12) on the susceptibility to cardiovascular metabolic disorders, including coronary artery disease, heart failure, ischemic stroke, and type 2 diabetes., Methods: We employed a two-sample Mendelian randomization (MR) analysis, utilizing inverse variance weighting and conducting comprehensive sensitivity assessments. We obtained publicly accessible summary data from separate cohorts comprising individuals of European ancestry. The level of statistical significance was established at a threshold of P < 0. 00074., Results: Based on our research findings, we have established a causal association between the consumption of circulating fat and the development of cardiovascular and metabolic diseases. The study found that an increase of one standard deviation in fat consumption was associated with a decreased risk of heart failure, with an odds ratio of 0. 56 (95 % CI: 0. 40-0. 79; p = 0. 0007). Notably, various sensitivity analyses confirmed the robustness of this association. Conversely, we did not find any significant correlation between other dietary components and the risk of cardiovascular and metabolic disorders., Conclusion: Our research findings demonstrate a conspicuous impact of dietary fat consumption on the susceptibility to heart failure, independent of coronary artery disease, diabetes, and stroke. Consequently, it is indicated that dietary factors are unrelated to the predisposition to cardiovascular metabolic disorders., 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 Inc.)

Background: Endoscopic nipple-sparing mastectomy (E-NSM) is a promising procedure in the treatment of breast cancer, but the limitations of endoscopic tools and intrinsic technical complexity of the technique hinder its applicability. Here, we introduce a novel surgery, gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), for breast cancer. and early effects., Methods: A retrospective analysis of the clinical data of 11 female patients, aged 50 (27-78) years, admitted to our hospital from January to December 2022, who underwent gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), was conducted. This study was designed to assess patient satisfaction before and after breast reconstruction, early complications, and breast function., Results: The tumors were all solitary, with a mean maximum diameter of 1.0 (0-2.0) cm and a mean distance of 2.3 (2-4) cm from the nipple, the mean intraoperative bleeding volume was 47.5 mL, and the mean hospital stay was 1.5 d. Postoperatively, 1 patient developed depigmentation of the nipple due to mild ischemia. There were no incisional complications, subcutaneous emphysema, infection, areola necrosis, skin flap necrosis, or removal of the prosthesis and/or patch. No tumor recurrence or metastasis was observed during the follow-up period. The difference between breast satisfaction and psychosocial health scores was not statistically significant ( P  = 0.680; P  = 0.612)., Conclusion: GETSMIRI, immediate implantable breast reconstruction, is less invasive than other such procedures, and short-term follow-up results show good postoperative satisfaction, making it an alternative surgical method., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

As a pathological hallmark of type 2 diabetes mellitus (T2DM), islet amyloid is formed by the aggregation of islet amyloid polypeptide (IAPP). Endoplasmic reticulum (ER) stress interacts with IAPP aggregates and has been implicated in the pathogenesis of T2DM. To examine the role of ER stress in T2DM, we cloned the hIAPP promoter and analyzed its promoter activity in human β-cells. We found that ER stress significantly enhanced hIAPP promoter activity and expression in human β-cells via triggering X-box binding protein 1 (XBP1) splicing. We identified a binding site of XBP1 in the hIAPP promoter. Disruption of this binding site by substitution or deletion mutagenesis significantly diminished the effects of ER stress on hIAPP promoter activity. Blockade of XBP splicing by MKC3946 treatment inhibited ER stress-induced hIAPP up-regulation and improved human β-cell survival and function. Our study uncovers a link between ER stress and IAPP at the transcriptional level and may provide novel insights into the role of ER stress in IAPP cytotoxicity and the pathogenesis of T2DM., (© 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: At present, good results have been obtained in the treatment of hematogenous osteomyelitis(HO) in children by the use of drug-loaded calcium sulfate, but there are few clinical studies reported. The aim of this study was to investigate the clinical efficacy of radical debridement combined with drug-laden calcium sulphate antibiotics in paediatric haematogenous osteomyelitis., Methods: In this study, we retrospectively analyzed the clinical data of 15 cases of pediatric hematogenous osteomyelitis admitted to our hospital in recent years. A total of 15 pediatric patients with HO treated in our hospital from January 2018 to February 2022 were included for evaluation., Results: All 15 patients were treated with drug-laden calcium sulfate, and the antibiotic of choice was vancomycin in 14 cases and vancomycin combined with gentamicin in 1 case. The follow-up period ranged from 12 to 36 months, with a mean follow-up time of 24.73 months, and all children were treated with drug-laden calcium sulfate with satisfactory clinical outcomes. The results of serological examination showed that the preoperative white blood cell count level, C-reactive protein and erythrocyte sedimentation rate were higher than the postoperative ones, and the differences were statistically significant (P < 0.05).After the operation, referring to the treatment standard of McKee's osteomyelitis, 15 cases were cured without recurrence; According to the Lower Extremities Functional Scale, 12 cases were excellent, 2 cases were good and 1 case was moderate, with an excellent rate of 93.33%. Children with lower limb involvement could walk with full weight bearing, and gait was basically normal., Conclusion: Drug-loaded calcium sulfate is a good therapeutic method for the treatment of hematogenous osteomyelitis in children, with a effect of reducing complications and reducing recurrence., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Coating the perovskite layer via a two-step method is an adaptable solution for industries compared to the anti-solvent process. But what about the impact of unreacted PbI 2 ? Usually, it is generated during perovskite conversion in a two-step method and considered beneficial within the grain boundaries, while also being accused of enhancing the interface defects and nonradiative recombination. Several additives are mixed in PbI 2 precursors for the purpose of improving the perovskite crystallinity and hindering the Pb 2+ defects. Herein, in lieu of adding additives to the PbI 2 , the effects of the PbI 2 residue via the electron transport layer/perovskite interface modification are explored. Consequently, by introducing artemisinin decorated with hydrophobic alkyl units and a ketone group, it reduces the residual PbI 2 and improves the perovskites' crystallinity by coordinating with Pb 2+ . In addition, artemisinin-deposited perovskite enhances both the stability and efficiency of perovskite solar cells by suppressing nonradiative recombination.

Gastroesophageal reflux-related cough is a multidisciplinary disease that cannot be diagnosed solely based on typical reflux-related symptoms. Its current diagnostic methods and criteria are largely derived from those used for gastroesophageal reflux disease, with slight differences. Esophageal reflux monitoring can provide objective evidence for the diagnosis of gastroesophageal reflux-related cough and is therefore the first-choice of laboratory tests recommended by the guidelines for cough management. Acid exposure time and syndrome association probability have been accepted as the diagnostic criteria, while esophageal motility assessment also has some certain auxiliary diagnostic value. Based on the existing evidence, we have reviewed how to improve the diagnostic methods and criteria for gastroesophageal reflux-related cough, as well as the issues that need to be addressed in the future.

Objective: To investigate the characteristics of esophageal dysmotility in patients with an initial diagnosis of acid/non-acid gastroesophageal reflux-related cough (GERC), and its correlation with the therapeutic response to anti-reflux treatments to search for the useful indicators to screen patients with chronic cough suitable for anti-reflux therapy. Methods: A total of 173 patients with suspicious GERC who attended the Chronic Cough Specialist Clinic of Department of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University between June 2020 and December 2022 were retrospectively selected for the study. The age of the patients was (45.1±14.6) years old, including 87 males and 86 females. Their demographic characteristics, clinical manifestations, and the results of high-resolution manometry (HRM) and multichannel intraluminal impedance-pH monitoring (MII-pH) were collected. Information on the etiological identification process and final diagnosis was also recorded. The recruited cases were grouped according to therapeutic outcomes and divided into cases with a favourable response to conventional anti-reflux treatment, cases with a favourable response to intensified anti-reflux treatment, and cases with no response to anti-reflux treatment. Factors influencing the efficacy of anti-reflux treatment were investigated. Differences between groups were compared using the χ 2 test, Student-Newman-Keuls test, and Kruskal-Wallis H ( K ) test, where applicable. Logistic regression analysis using forward stepwise regression based on maximum likelihood estimation was used to screen for influence factors. Results: The 175 patients with suspicious GERC included 45 (26.0%) patients who responded to conventional anti-reflux treatment, 54 (31.2%) who responded to intensified anti-reflux treatment and 74 (42.8%) who did not respond to anti-reflux therapies. Esophageal dysmotility was present in 52.0% of patients (90/173), but was less common in patients who responded to conventional anti-reflux treatment ( χ 2 =8.09, P= 0.018). Although the majority of reflux episodes were non-acid (136/173, 78.6%), the proportion of acid reflux ( χ 2 =19.49, P <0.001) and acid exposure time ( H= 11.04, P= 0.078), with a shorter break [2.4 (0.7, 5.6) cm vs. 48.5%, χ 2 =3.11, P= 0.078), with a shorter break [2.4 (0.7, 5.6) cm vs. 6.1 (1.4, 10.0) cm, Z= -2.39, P= 0.017], longer upper esophageal sphincter [(4.1±0.9) cm vs. (3.7±1.3) cm, t= -2.09, P= 0.038], higher percentage of normal esophageal contractions [60.0% (17.8%, 90.0%) vs. 30.0% (0, 80.0%), Z= -2.14, P= 0.032], and lower percentage of large break [10.0% (0, 40.0%) vs. 50.0% (0, 100.0%), Z= -2.92, P= 0.014) in the patients who responded to intensified anti-reflux treatment and in the patients who did not respond to the anti-reflux therapies. Multifactorial logistic regression analysis identified the percentage of ineffective contraction as an independent factor predicting the efficacy of conventional anti-reflux treatment, with a cut-off value of≤45% and a moderate predictive value (AUC=0.67, H= 7.49, P= Esophageal dysmotility is common in GERC patients with different characteristics in acid and non-acid GERC. The percentage of ineffective esophageal contraction may be a useful indicator for selecting an anti-reflux strategy and predicting treatment outcomes.H= 8.60, P= 0.014) in the patients who responded to intensified anti-reflux treatment and in the patients who did not respond to the anti-reflux therapies. Multifactorial logistic regression analysis identified the percentage of ineffective contraction as an independent factor predicting the efficacy of conventional anti-reflux treatment, with a cut-off value of≤45% and a moderate predictive value (AUC=0.67, P= 0.004). Conclusions: Esophageal dysmotility is common in GERC patients with different characteristics in acid and non-acid GERC. The percentage of ineffective esophageal contraction may be a useful indicator for selecting an anti-reflux strategy and predicting treatment outcomes.

Background: This study aimed to examine glycolysis/gluconeogenesis-related genes in hepatocellular carcinoma (HCC) and evaluate their potential roles in HCC progression and immunotherapy response., Methods: Data analyzed in this study were collected from GSE14520, GSE76427, GSE174570, The Cancer Genome Atlas (TCGA), PXD006512, and GSE149614 datasets, metabolic pathways were collected from MSigDB database. Differentially expressed genes (DEGs) were identified between HCC and controls. Differentially expressed glycolysis/gluconeogenesis-related genes (candidate genes) were obtained and consensus clustering was performed based on the expression of candidate genes. Bioinformatics analysis was used to evaluate candidate genes and screen prognostic genes. Finally, the key results were tested in HCC patients., Results: Thirteen differentially expressed glycolysis/gluconeogenesis-related genes were validated in additional datasets. Consensus clustering analysis identified two distinct patient clusters (C1 and C2) with different prognoses and immune microenvironments. Immune score and tumor purity were significantly higher in C1 than in C2, and CD4+ memory activated T cell, Tfh, Tregs, and macrophage M0 were higher infiltrated in HCC and C1 group. The study also identified five intersecting DEGs from candidate genes in TCGA, GSE14520, and GSE141198 as prognostic genes, which had a protective role in HCC patient prognosis. Compared with the control group, the prognostic genes all showed decreased expression in HCC patients in RT-qPCR and Western blot analyses. Flow cytometry verified the abnormal infiltration level of immune cells in HCC patients., Conclusion: Results showed that glycolysis/gluconeogenesis-related genes were associated with patient prognosis, immune microenvironment, and response to immunotherapy in HCC. It suggests that the model based on five prognostic genes may valuable for predicting the prognosis and immunotherapy response of HCC 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., (Copyright © 2023 Chen, Aierken, Li, Chen, Ren and Wang.)

Background: Community practice training is an important part of education in medicine, public health, social medicine, and other disciplines. The objective of this study is to explore the effect and importance of the community practice of Master of Public Health graduates on community residents' health during the Coronavirus Disease 2019 pandemic., Methods: This study used a pretest-posttest design. A total of 152 participants with age ≥ 60 years were selected using a multistage sampling method from Hangzhou in China. Baseline and endline data were collected using structured questionnaires by face-to-face interviews. All psychological and behavioral measurements were performed using standardized instruments and showed good reliability and validity. A total of 147 participants were included in the analysis. The chi-square and rank sum tests were used to compare the difference between baseline and endline for categorical variables. Binary logistic regression analysis was used to evaluate the association between community practice training and changes in psychology and behavior., Results: The result of chi-square test revealed a statistically significant difference in participants' eating habits from baseline to endline. Participants reported that the self-perceived health status was different between endline and baseline by the rank sum test. The results of logistic regression analysis showed that community practice training was significantly associated with increased self-efficacy scores, cognitive function and eating habits, with odd ratios of 1.08, 0.90 and 1.93, respectively., Conclusions: Community practice training was associated with changes in health behavior and psychology of community residents. Our results suggested enhanced community practice training for students under the Master of Public Health program., (© 2023. The Author(s).)

Posttraumatic stress disorder (PTSD) is a psychiatric disorder that is associated with long-lasting memories of traumatic experiences. Extinction and discrimination of fear memory have become therapeutic targets for PTSD. Newly developed optogenetics and advanced in vivo imaging techniques have provided unprecedented spatiotemporal tools to characterize the activity, connectivity, and functionality of specific cell types in complicated neuronal circuits. The use of such tools has offered mechanistic insights into the exquisite organization of the circuitry underlying the extinction and discrimination of fear memory. This review focuses on the acquisition of more detailed, comprehensive, and integrated neural circuits to understand how the brain regulates the extinction and discrimination of fear memory. A future challenge is to translate these researches into effective therapeutic treatment for PTSD from the perspective of precise regulation of the neural circuits associated with the extinction and discrimination of fear memories.

Bacterial or viral infections, such as Brucella , mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1 , an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1 - Spry1 -NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Luminescence thermometry using sharp line emission of lanthanide ions has become an active area of research as it offers the advantages of remote temperature sensing with high sensitivity and superior spatial resolution. The most widely applied method relies on the temperature dependence of the luminescence intensity ratio of emission lines from two thermally coupled levels. However, the usable temperature range for this type of Boltzmann thermometer is limited. In addition, the weak and narrow line absorption of the parity forbidden 4f-4f transitions of lanthanides forms a serious drawback. To solve both problems, we here report a new dual functionality luminescence thermometer: Gd 2 O 2 S co-doped with Eu 3+ and Nd 3+ . This material combines Boltzmann and energy transfer thermometry to extend the temperature range and uses the strong and broad charge transfer absorption band of Eu 3+ for sensitization. In the T-range of 300-500 K efficient energy transfer from Eu 3+ to Nd 3+ allows for charge transfer-sensitized luminescence thermometry using near infrared emission from the thermally coupled 4 F 3/2 and 4 F 5/2 levels of Nd 3+ . Above 500 K a high temperature sensitivity is obtained using the strong temperature dependence of the luminescence intensity ratio of red Eu 3+ to near infrared Nd 3+ emission. The dual-functionality provides a single thermometer combining strong absorption and high relative sensitivity (0.6 - 1.4%) over a wide temperature range (300 to 650 K). Finally, it is proposed that this dual-function luminescent thermometer has promising potential for multifunctional applications in biosensors and in situ temperature measurements of chemical reaction process., 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 Elsevier Inc. All rights reserved.)

The existing treatment modalities for skin injuries mainly include dressings, negative-pressure wound treatment, autologous skin grafting, and high-pressure wound treatment. All of these therapies have limitations such as high time cost, the inability to remove inactivated tissue in a timely manner, surgical debridement, and oxygen toxicity. Mesenchymal stem cells have a unique self-renewal ability and wide differentiation potential, and they are one of the most promising stem cell types in cell therapy and have great application prospects in the field of regenerative medicine. Collagen exerts structural roles by promoting the molecular structure, shape, and mechanical properties of cells, and adding it to cell cultures can also promote cell proliferation and shorten the cell doubling time. The effects of collagen on MSCs were examined using Giemsa staining, EdU staining, and growth curves. Mice were subjected to allogeneic experiments and autologous experiments to reduce individual differences; all animals were separated into four groups. Neonatal skin sections were detected by HE staining, Masson staining, immunohistochemical staining, and immunofluorescence staining. We found that the MSCs pretreated with collagen accelerated the healing of skin wounds in mice and canines by promoting epidermal layer repair, collagen deposition, hair follicle angiogenesis, and an inflammatory response. Collagen promotes the secretion of the chemokines and growth factors associated with skin healing by MSCs, which positively influences skin healing. This study supports the treatment of skin injuries with MSCs cultured in medium with collagen added.

Background and Objective: Gastroesophageal reflux disease (GERD)-associated cough is defined as a special GERD with a predominant cough symptom and is a common cause of chronic cough. This review summarizes our current understanding on the pathogenesis and management of GERD-associated cough., Methods: Main literatures on the pathogenesis and management of GERD-associated cough were reviewed and our understandings derived from the published studies were showed then., Key Content and Findings: Although esophageal-tracheobronchial reflex mainly underlies the pathogenesis of GERD-associated cough, its counterpart-tracheobronchial-esophageal reflex might exist and initiate the cough due to reflux induced by upper respiratory tract infection through the signaling of transient receptor potential vanilloid 1 linking airway and esophagus. The presence of reflux-associated symptoms such as regurgitation and heartburn along with coughing suggests an association between cough and GERD, which is supported by the objective evidence of abnormal reflux as detected by reflux monitoring. Although there is no general consensus, esophageal reflux monitoring provides the main diagnostic criteria for GERD-associated cough. Despite that acid exposure time and symptom associated probability are useful and mostly employed reflux diagnostic criteria, they are imperfect and far from being the gold standard. Acid suppressive therapy has long been recommended as the first choice for GERD-associated cough. However, the overall benefits of proton pump inhibitors have been controversial and need to be further assessed, especially in patients with cough due to non-acid reflux. Neuromodulators have demonstrated potential therapeutic effects for refractory GERD-associated cough, for which anti-reflux surgery may also be a promising treatment option., Conclusions: Tracheobronchial-esophageal reflex might initiate reflux-induced cough provoked by the upper respiratory tract infection. It is necessary to optimize the current standards and to explore new criteria with higher diagnostic potency. Acid suppressive therapy is the first choice for GERD-associated cough, followed by neuromodulators and anti-reflux surgery for refractory GERD-associated cough., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1757/coif). The series “Novel Insights Into Chronic Cough” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: The community environment plays a vital role in the health of older adults. During the COVID-19 epidemic, older adults, who were considered the most impacted and most vulnerable social group, were confined to their homes during the implementation of management and control measures for the epidemic. In such situations, older adults may have to contend with a lack of resources and experience anxiety. Therefore, identifying the environmental factors that are beneficial for their physical and mental health is critical., Objective: This study aimed to assess the association between community cohesion and the physical and mental health of older adults and to identify the related community services and environmental factors that may promote community cohesion., Methods: This community-based cross-sectional study was designed during the COVID-19 epidemic. A multistage sampling method was applied to this study. A total of 2036 participants aged ≥60 years were sampled from 27 locations in China. Data were collected through face-to-face interviews. The neighborhood cohesion instrument consisting of scales on 3 dimensions was used to assess community cohesion. Self-efficacy and life satisfaction, cognitive function and depression, and community services and environmental factors were also measured using standard instruments. Statistical analyses were restricted to 99.07% (2017/2036) of the participants. Separate logistic regression analysis was conducted to assess the association among community cohesion and physical and mental health factors, related community services, and environmental factors among older adults., Results: The results showed that high levels of community cohesion were associated with good self-perceived health status and life satisfaction (odds ratio [OR] 1.27, 95% CI 1.01-1.59 and OR 1.20, 95% CI 1.15-1.27, respectively) and high levels of self-efficacy and psychological resilience (OR 1.09, 95% CI 1.05-1.13 and OR 1.05, 95% CI 1.03-1.06, respectively). The length of stay in the community and the level of physical activity were positively associated with community cohesion scores, whereas the education level was negatively associated with community cohesion scores (P=.009). Community cohesion was also associated with low levels of depression and high levels of cognitive function. Community cohesion was significantly associated with community services and environmental factors on 4 dimensions. High levels of community cohesion were associated with transportation services and rehabilitation equipment rental services as well as high levels of satisfaction with community physicians' technical expertise and community waste disposal (OR 3.14, 95% CI 1.87-5.28; OR 3.62, 95% CI 2.38-5.52; OR 1.37, 95% CI 1.08-1.73; and OR 1.23, 95% CI 1.01-1.50, respectively)., Conclusions: Community cohesion was found to be associated with the physical and mental health of older adults. Our research suggests that enhancing community services and environmental resources may be an effective strategy to increase community cohesion during major infectious disease epidemics., (©Ying Li, XiWen Ding, Ayizuhere Aierken, YiYang Pan, Yuan Chen, DongBin Hu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 14.04.2023.)

Objectives: Previous studies have suggested that heart rate and blood pressure play important roles in the development of adverse outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the relationship between the rate pressure product (RPP) and long-term outcomes has rarely been investigated. This study investigated the effects of RPP on the clinical outcomes of patients with CAD who underwent PCI., Design: In this study, a total of 6015 patients with CAD were enrolled. All patients were from the CORFCHD-PCI (Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI) Study. They were divided into two groups according to RPP (RPP <10 269, n=4018 and RPP ≥10 269, n=1997). In addition, the median follow-up time was 32 months., Participants: Data was obtained from 6050 patients with CAD who underwent PCI at the First Affiliated Hospital of Xinjiang Medical University from January 2008 to December 2016., Primary and Secondary Outcome Measures: The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs)., Results: We found that there were significant differences between the two groups in the incidence of ACM, CM, MACCEs and MACEs (all p<0.05). Among the patients with CAD having ACM, CM, MACCEs and MACEs, the mean survival time of the low-value group was significantly higher than that of the high-value group. Multivariate Cox regression analyses showed that RPP was an independent predictor for ACM (HR=1.605, 95% CI: 1.215-2.120, p=0.001), CM (HR=1.733, 95% CI: 1.267-2.369, p=0.001), MACCEs (HR=1.271, 95% CI: 1.063-1.518, p=0.008) and MACEs (HR=1.315, 95% CI: 1.092-1.584, p=0.004) in patients with stable CAD. On the other hand, there was no significant correlation between the RPP and the adverse outcomes in patients with acute coronary syndrome., Conclusion: In summary, RPP is an independent predictor of long-term prognosis in patients with CAD who underwent PCI. A higher baseline RPP before PCI increased the risk of adverse outcomes. Compared with heart rate and blood pressure alone, RPP has a higher predictive value for adverse clinical outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

This paper investigated the influence of dry-wet cycles and sulfate attack on the performance of magnesium potassium phosphate cement (MKPC) as well as the effect of waterglass on MKPC. X-ray diffraction (XRD), TG-DTG, and scanning electron microscopy (SEM-EDS) were used to examine the phase composition and microstructure of MKPC. The results showed that the flexural and compressive strength of an MKPC paste increased initially and subsequently decreased in different erosion environments. The final strength of the M0 paste exposed to the SK-II environment was the highest, while that of the M0 paste exposed to the DW-II environment was the lowest. The final volume expansion value of MKPC specimens under four corrosion conditions decreased in the following order: DW-II, M0 > SK-II, M0 > DW-II, M1 > SK-I, M0 > DW-I, M0. Compared to the full-soaking environment, the dry-wet cycles accelerated sulfate erosion and the appearance of damages in the macro and micro structure of the MKPC paste. With the increase in the number of the dry and wet cycles, more intrinsic micro-cracks were observed, and the dissolution of hydration products was accelerated. Under the same number of dry-wet cycles, the strength test and volume stability test showed that the durability in a Na 2 SO 4 solution of the MKPC paste prepared with 2% waterglass (M1) was superior to that of the original M0 cement. The micro analysis indicated that waterglass can improve the compactness of the microstructure of MPC and prevent the dissolution of struvite-K.

Background: The deregulated genetic factors are critically associated with idiopathic pulmonary arterial hypertension (IPAH) development and progression. However, the identification of hub-transcription factors (TFs) and miRNA-hub-TFs co-regulatory network-mediated pathogenesis in IPAH remains lacking., Methods: We used GSE48149, GSE113439, GSE117261, GSE33463, and GSE67597 for identifying key genes and miRNAs in IPAH. We used a series of bioinformatics approaches, including R packages, protein-protein interaction (PPI) network, and gene set enrichment analysis (GSEA) to identify the hub-TFs and miRNA-hub-TFs co-regulatory networks in IPAH. Also, we employed a molecular docking approach to evaluate the potential protein-drug interactions., Results: We found that 14 TFs encoding genes, including ZNF83, STAT1, NFE2L3, and SMARCA2 are upregulated, and 47 TFs encoding genes, including NCOR2, FOXA2, NFE2, and IRF5 are downregulated in IPAH relative to the control. Then, we identified the differentially expressed 22 hub-TFs encoding genes, including four upregulated (STAT1, OPTN, STAT4, and SMARCA2) and 18 downregulated (such as NCOR2, IRF5, IRF2, MAFB, MAFG, and MAF) TFs encoding genes in IPAH. The deregulated hub-TFs regulate the immune system, cellular transcriptional signaling, and cell cycle regulatory pathways. Moreover, the identified differentially expressed miRNAs (DEmiRs) are involved in the co-regulatory network with hub-TFs. The six hub-TFs encoding genes, including STAT1, MAF, CEBPB, MAFB, NCOR2, and MAFG are consistently differentially expressed in the peripheral blood mononuclear cells of IPAH patients, and these hub-TFs showed significant diagnostic efficacy in distinguishing IPAH cases from the healthy individuals. Moreover, we revealed that the co-regulatory hub-TFs encoding genes are correlated with the infiltrations of various immune signatures, including CD4 regulatory T cells, immature B cells, macrophages, MDSCs, monocytes, Tfh cells, and Th1 cells. Finally, we discovered that the protein product of STAT1 and NCOR2 interacts with several drugs with appropriate binding affinity., Conclusions: The identification of hub-TFs and miRNA-hub-TFs co-regulatory networks may provide a new avenue into the mechanism of IPAH development and pathogenesis.

Current measures mainly focus on how melatonin reduces physiological heat stress in animals, but its effects on reproductive damage to male dairy goats have been neglected. This study aimed to determine the protective effect of melatonin on male reproduction during heat stress in dairy goats and to further explore its mechanisms. A natural heat stress model of Saanen dairy goats was used to assess testicular tissue damage 7 days after heat stress and to examine semen quality changes during a spermatogenic cycle. RNA-seq, Western blot, RT-qPCR, and immunofluorescence staining were used to explore the mechanism by which melatonin protects against heat stress-induced reproductive damage and to validate the results. The data suggested that melatonin significantly alleviated the heat stress-induced decrease in sperm quality, protected varicose tubule structure, reduced the levels of heat shock proteins and apoptotic proteins and protected the spermatocytes and round spermatozoa, which are mainly affected by heat stress. RNA-seq results suggest that melatonin inhibits the PI3K/AKT signaling pathway, reduces the level of p-AKT, and promotes elevated BCL-2. In addition, melatonin treatment could upregulate the gene expression of MT2 which was downregulated by heat stress and improve the change in extracellular matrix components and restore serum testosterone levels. Our results suggest that melatonin can protect against testicular and spermatogenic cell damage and improve semen quality in male dairy goats under heat stress. This study provides an important reference for subsequent studies on the molecular mechanisms of melatonin in protecting male reproductive processes under heat stress and using exogenous melatonin to prevent heat stress., (© 2022. The Author(s).)

Laparoscopic surgery could be considered as an art of geometric algebra. However, very little is studied in the context of bariatric surgery. The current study aims to explore the possible influence concept of geometric algebra on the surgical process in the overweight and obese patients in the setting of laparoscopic sleeve gastrectomy (LSG). During the study period, clinical data of subjects who underwent LSG was retrospectively analyzed. Parameters examined include body mass index (BMI), umbilical-xiphoidal interval (U-X) and umbilical-fundus (U-F) interval. In this study, LSG was performed via central view approach (C) and left view approach (L). In both groups, the body surface projection points of viewing hole (V), main and accessory operating holes (O1 and O2) and surface display of fundus (F) were connected to form a geometric figure. The accessibility of the surgical instrument into the fundus, the need for elongated instruments and related intra- and post-operative parameters were noted. The overweight and obese subjects showed a significant increased U-X and U-F interval compared to the non-obese subjects. The length of both U-X and U-F interval were correlated with the BMI. The geometric figure is quite different between L and C approach with significant increase of area of quadrangle. Significant longer O1-F, O2-F and V-F interval was calculated in C approach of patients and thus the elongated instruments were frequently required. The integration of the concept geometric algebra with the proper selection of troca may provide a better surgical experience and smooth surgical process., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

In women, excess androgen causes polycystic ovary syndrome (PCOS), a common fertility disorder with comorbid metabolic dysfunctions including diabetes, obesity, and nonalcoholic fatty liver disease. Using a PCOS mouse model, this study shows that chronic high androgen levels cause hepatic steatosis while hepatocyte-specific androgen receptor (AR)-knockout rescues this phenotype. Moreover, through RNA-sequencing and metabolomic studies, we have identified key metabolic genes and pathways affected by hyperandrogenism. Our studies reveal that a large number of metabolic genes are directly regulated by androgens through AR binding to androgen response element sequences on the promoter region of these genes. Interestingly, a number of circadian genes are also differentially regulated by androgens. In vivo and in vitro studies using a circadian reporter [Period2::Luciferase (Per2::LUC)] mouse model demonstrate that androgens can directly disrupt the hepatic timing system, which is a key regulator of liver metabolism. Consequently, studies show that androgens decrease H3K27me3, a gene silencing mark on the promoter of core clock genes, by inhibiting the expression of histone methyltransferase, Ezh2, while inducing the expression of the histone demethylase, JMJD3, which is responsible for adding and removing the H3K27me3 mark, respectively. Finally, we report that under hyperandrogenic conditions, some of the same circadian/metabolic genes that are upregulated in the mouse liver are also elevated in nonhuman primate livers. In summary, these studies not only provide an overall understanding of how hyperandrogenism associated with PCOS affects liver gene expression and metabolism but also offer insight into the underlying mechanisms leading to hepatic steatosis in PCOS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI., Methods: The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEVs., Results: Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose, D-Glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats., Conclusions: We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future., (© 2022. The Author(s).)

Children aged 6-11 years with uncontrolled asthma are treated with low-dose inhaled corticosteroid (ICS) with stepwise increase in ICS dosage and/or add-on maintenance treatment, as necessary. The objective of the present study was to evaluate the efficacy and safety of tiotropium add-on treatment in children with severe and mild symptomatic asthma. The present prospective cohort study included 144 children with severe and mild asthma (age, 6-11 years) who received ICS (budesonide) with ≥1 controller treatment combination therapies for ≥1 month and score ≥1.5 based on Asthma Control Questionnaire-Interviewer-Administered. In addition to ICS with ≥1 controller treatment, children received 5 µg once-daily tiotropium (treatment group; n=72) or did not receive tiotropium (control group; n=72). The peak forced expiratory volume in 1-sec change from the baseline 3 h post-administration of tiotropium was significantly improved in the treatment group compared with the control group (384±31 vs. 248±28 ml; P<0.0001). The trough forced expiratory volume in 1-sec (224±28 vs. 140±31 ml; P<0.0001) and forced expiratory flow at 25-75% of forced vital capacity (389±36 vs. 116±27 ml/sec; P<0.0001) showed significant improvement following treatment with tiotropium. Significant differences were noted for trough forced vital capacity (153±29 vs. 139±30 ml/sec; P<0.0001), mean weekly rescue treatment usage (0.29±0.08 vs. 0.36±0.09; P<0.0001), mean weekly peak expiratory flow measurement (4.12±3.56 vs. 7.46±3.29 l/min; P<0.0001) and mean weekly symptom-free time (0.19±0.04 vs. 0.16±0.04 days; P<0.0001) between both cohorts. Children of both groups tolerated any adverse effects. Tiotropium 5 µg administered once/day as an add-on treatment to ICS with ≥1 controller treatments in children (6-11 years of age) with severe and mild symptomatic asthma was found to be efficacious and safe (level of evidence 2; technical efficacy stage 4)., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020, Spandidos Publications.)

Background: The prevalence of dependency personality disorder (DPD) is high among elderly people living in rural areas. This study aims to explore the association between dependency on community resources and social support among elderly individuals living in rural areas., Methods: A cross-sectional study was conducted in 26 locations in China. A total of 1160 participants aged ≥ 60 years were selected using a complex multistage sampling design. All data were obtained using questionnaires via face-to-face interviews. DPD was measured using the Minnesota Multiphasic Personality Inventory-II in the standardized Chinese version. Self-efficacy was assessed using the Chinese version of the General Self-Efficacy Scale. Social support was measured using the Chinese version of the questionnaires of the Older American Resources and Services scale. Community services and resources comprised 44 items. The association between DPD and levels of social support and self-efficacy was evaluated using a logistic regression model. The association between social support and self-efficacy was assessed using analysis of covariance., Results: Univariate analysis results showed that elderly people living in rural areas had higher DPD scores and lower levels of self-efficacy compared with those living in urban areas (P < 0.001). Logistic regression analysis showed that DPD was positively associated with the received frequencies of community health service, contracted family doctor services, and regular lectures on health knowledge among the elderly people with odd ratios of 1.58 (P < 0.001), 2.03 (P = 0.013), and 2.67 (P = 0.005), respectively. Logistic regression analysis showed significant interaction between social support and self-efficacy effect on DPD was found in the additive model (P < 0.001)., Conclusion: DPD was associated mainly with the community resources among elderly people living in rural areas. Social support and self-efficacy were commonly associated with DPD through a synergistic effect. These results suggest that DPD among elderly people may be reduced through effective social support to directly and indirectly promote the elderly's use of community resources and improve their self-efficacy., (© 2022. The Author(s).)

In this study, we used the polysaccharide ulvan from the green macroalgae Ulva fenestrata to prepare the hydrogel for chronic diabetic wound healing. A natural polysaccharide-based hydrogel matrix (UC-DPA-Ag hydrogel) was prepared using ulvan dialdehyde, chitosan, dopamine (DPA) and silver nanoparticles (Ag NPs). Human umbilical cord mesenchymal stem cell lyophilized powder (hUC-MSCs) was loaded into the hydrogel to develop a novel chronic diabetic wound healing material (UC-DPA-Ag@hUC-MSCs). The resulting hydrogel features adequate mechanical properties, swelling capability, adhesiveness, antioxidant, antibacterial ability, and promoting cell proliferation and migration. In vivo wound healing in type II diabetic mellitus mouse wound model showed that hUC-MSCs loaded UC-DPA-Ag hydrogel could accelerate wound healing effectively. This advanced hydrogel provides a facile and effective way for diabetic chronic wound management. Furthermore, it offers a new route for the utilizing Ulva as a valuable biomaterial for the global and large-scale production of valued added biomaterials., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The effect of socioeconomic status (SES) on dependency is still complex and not fully clear. The purposes of this study are to assess the association between SES and dependency personality disorder (DPD) using both objective and subjective assessments., Methods: A cross-sectional study was conducted in 27 locations in China among 1,276 general residents aged 60 years and above through a complex multistage sampling design. Data were collected using a questionnaire by well-trained investigators through face-to-face interviews. The DPD was assessed using a standardized Chinese version of the Minnesota Multiphasic Personality Inventory-II scale. Objective SES was assessed by the combination of education levels, individual income, preretirement occupation, and medical insurance. Subjective SES was measured using the MacArthur Scale. The logistic regression analysis was used to evaluate the association between objective SES and DPD. Analysis of covariance was conducted to compare the mean of DPD scores in different levels of SES., Results: The results of the chi-squared test showed that the levels of objective SES were associated with DPD, depression, social resources, and region. The logistic regression analysis showed a significant negative association between the levels of objective SES and DPD. The odds ratio was 1.84 (95% confidence interval, 1.07-3.18) after adjusting for important confounding factors. The analysis of covariance showed differences in the mean of DPD scores among different groups defined by different levels of SES., Conclusion: The levels of SES were negatively associated with DPD, and subjective SES had a stronger association with DPD than objective SES. The effect of subjective SES on DPD is possibly associated with the perception of position in the social hierarchy., 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 Pan, Aierken, Ding, Chen and Li.)

Ferroptosis is a relatively novel form of regulated cell death that was discovered in 2012. With the increasing research related to the mechanisms of ferroptosis, previous studies have demonstrated that the inactive of the intracellular antioxidant system and iron overload can result in the accumulation of reactive oxygen species (ROS), which can ultimately cause lipid peroxidation in the various cell types of the body. ROS accumulation can cause sperm damage by attacking the plasma membrane and damaging DNA. Acute ferroptosis causes oxidative damage to sperm DNA and testicular oxidative stress, thereby causing male reproductive dysfunction. This review aims to discuss the metabolic network of ferroptosis, summarize and analyze the relationship between male reproductive diseases caused by iron overload as well as lipid peroxidation, and provide a novel direction for the research and prevention of various male reproductive diseases.