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The typical clinical characteristic of patients with anti-IFN-γ autoantibodies (AIGAs) is primarily associated with infection caused by intracellular pathogens. With continued research, additional clinical characteristics have been gradually uncovered. Here, we present a case of multiple pathogen infections accompanied by ocular pathologies in a patient with high titers of AIGAs. The patient, a 53-year-old female patient, was admitted to our hospital after finding a mass in the right supraclavicular fossa. She was successively diagnosed with Talaromyces marneffei, Aspergillus flavus and Nontuberculous mycobacteria (NTM) infections. Then, she received a complete course of antifungal agents for nearly 3.5 years and anti-NTM treatment for nearly 3 years, with discontinuation upon symptom improvement. However, there was a rapid recurrence of the infection upon cessation of the drug despite improvement in the patient's symptoms. Moreover, when the recurrent infection stabilized, the patient exhibited immune conjunctivitis and dry eye, which was successfully treated by tacrolimus eye drops and lubricant. Patients with high-titer AIGAs are more prone to experiencing recurrence and/or persistent infection, as well as immune disorders., Competing Interests: Declarations Ethics approval and consent to participate Informed consent was obtained from the patient to publish this case report in an online open-access publication. Patient had provided written consent to publish this case. Documentation is available upon request. All identifying information has been removed from the manuscript and figures. Informed consent was obtained from the patient to publish this case report in an online open-access publication. Consent for publication Written informed consent to have the case details and any accompanying images published has been provided by the patient. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Polyploid giant cancer cells (PGCCs) have properties of cancer stem cells (CSCs). PGCCs with daughter cells (PDCs) undergo epithelial-mesenchymal transition and show enhanced cellular plasticity. This study aimed to elucidate the mechanisms underlying the osteo/chondrogenic-like differentiation of PDCs, which may be exploited therapeutically by transdifferentiation into post-mitotic and functional cells., Methods: Cobalt chloride was used to induce PGCC formation in MDA-MB-231 and HEY cells, and PDCs were cultured in osteo/chondrogenic differentiation media. Alcian blue staining was used to confirm osteo/chondrogenic differentiation, and the cell cycle was detected using flow cytometry. The expression of osteo/chondrogenic differentiation-related proteins was compared, and a co-immunoprecipitation assay was used to demonstrate the interactions between proteins. Bioinformatic analysis was used to explore the regulatory mechanism of osteo/chondrogenic differentiation, and a dual-luciferase reporter assay was performed to validate the interaction between transcriptional factors and target genes. Animal xenograft models were used to confirm the osteo/chondrogenic differentiation of PDCs., Results: When cultured in osteo/chondrogenic medium, the stemness of PDCs decreased, and the expression of osteo/chondrogenic-related markers increased. This osteo/chondrogenic-like process was regulated by the transforming growth factor-β pathway in a time-dependent manner. A concurrent increase in the expression of histone acetyltransferase p300 and the transcription factor CCCTC-binding factor (CTCF) was observed. Co-immunoprecipitation assays revealed that p300 acetylated the osteo/chondrogenic marker RUNT-related transcription factor 2 (RUNX2). Analysis of chromatin immunoprecipitation sequencing datasets revealed that both CTCF and histone H3 lysine 27 acetylation (H3K27ac) were enriched in the promoter region of E1A-associated protein p300 (P300). The four predicted binding sites for CTCF and P300 were validated using dual-luciferase reporter assays. We examined the interaction between CTCF and H3K27ac and found that these two proteins had a combined effect on the transactivation of P300., Conclusion: CTCF, in synergy with H3K27ac, amplified the expression of P300, facilitating acetyl group transfer to RUNX2. This acetylation stabilized RUNX2 and promoted osteo/chondrogenic differentiation, thereby reducing the incidence of PDC malignancies., Competing Interests: Declarations Ethical approval The experimental protocol was established according to the ethical guidelines of the Declaration of Helsinki and was approved by the Medicine Ethics Committee of the Tianjin Union Medical Center. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to examine the association between the American Heart Association's (AHA) newly revised Life's Essential 8 (LE8) algorithm, designed for assessing cardiovascular health (CVH), and cognitive impairment among older adults in the United States., Methods: This study employed a cross-sectional design, utilizing data from the 2011-2014 National Health and Nutrition Examination Survey to explore the relationship between CVH and cognitive impairment in older adults. CVH scores are assessed based on the AHA definition of the LE8, categorized into three tiers: low (0-49), medium (50-79), and high (80-100). Cognitive impairment is evaluated using three distinct scoring systems: the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). The lowest quartile as the cut-off point; below or equal to the lower quartile was considered as low cognitive population, and above the lower quartile was normal population. To analyze the association, multivariable logistic regression and restricted cubic spline (RCS) models were employed., Results: A significant negative correlation exists between the LE8 and cognitive impairment. After adjusting for multiple variables, the odds ratios (OR) for cognitive impairment, as measured by the CERAD, AFT, and DSST, were compared between patients with high and low CVH. The results indicated OR values of 0.60 (95% CI: 0.36-0.98), 0.72 (95% CI: 0.52-0.97), and 0.29 (95% CI: 0.16-0.53) for the CERAD, AFT, and DSST, respectively. Additionally, the RCS curve demonstrated a significant linear relationship between lifestyle factors encapsulated by the LE8 and cognitive impairment., Conclusions: The findings indicate higher adherence to LE8 was associated with lower odds of cognitive impairment. Furthermore, maintaining optimal CVH is crucial in preventing cognitive impairment., Competing Interests: Declarations Ethics approval and consent to participate The studies involving human participants were reviewed and approved through the NHANES has been approved through the National Center for Health Statistics Research Ethics Review Board. All participants have provided their informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

Duck plague virus (DPV) causes the highly pathogenic duck plague, and the envelope glycoprotein I (gI), as one of the key virulence genes, has not yet had its critical virulence sites identified through screening. This study used reverse genetics technology to target the gI, specifically within the DPV genome. Four DPV mutants with gI N-glycosylation site mutations were designed and constructed, and these mutant strains were successfully rescued. Our results confirmed that three asparagine residues of gI (N 69 , N 78 , and N 265 ) are N-glycosylation sites, and western blot analysis substantiated that glycosylation at each predicted N-glycosylation site was compromised. The deglycosylation of gI leads to the protein misfolding and subsequent retention in the endoplasmic reticulum (ER). The subsequent deglycosylated gI is carried into the Golgi apparatus (GM130) in the interaction of gE. Compared to the parental virus, the mutated virus shows a 66.3% reduction in intercellular transmission capability. In ducks, the deglycosylation of gI significantly reduces DPV replication in vivo, thereby weakening the virulence of DPV. This study represents the first successful creation of a weak DPV virus strain by specific mutation at the N-glycosylation site. The findings provide a foundational understanding of DPV pathogenesis and form the basis for developing live attenuated vaccines against the disease., (© 2024. The Author(s).)

The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies., (© 2024. The Author(s).)

Objective: This study aims to assess the performance of various scoring systems in predicting the 28-day mortality of patients with aortic aneurysms (AA) admitted to the intensive care unit (ICU)., Methods: We utilized data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) to perform a comparative analysis of various predictive systems, including the Glasgow Aneurysm Score (GAS), Simplified Acute Physiology Score (SAPS) III, SAPS II, Logical Organ Dysfunction System (LODS), Sequential Organ Failure Assessment (SOFA), Systemic Inflammatory Response Syndrome (SIRS), and The Oxford Acute Illness Severity Score (OASIS). The discrimination abilities of these systems were compared using the area under the receiver operating characteristic curve (AUROC). Additionally, a 4-knotted restricted cubic spline regression was employed to evaluate the association between the different scoring systems and the risk of 28-day mortality. Finally, we conducted a subgroup analysis focusing on patients with abdominal aortic aneurysms (AAA)., Results: This study enrolled 586 patients with AA (68.39% male). Among them, 26 patients (4.4%) died within 28 days. Comparative analysis revealed higher SAPS II, SAPS III, SOFA, LODS, OASIS, and SIRS scores in the deceased group, while no statistically significant difference was observed in GAS scores between the survivor and deceased groups (P = 0.148). The SAPS III system exhibited superior predictive value for the 28-day mortality rate (AUROC 0.805) compared to the LODS system (AUROC 0.771), SOFA (AUROC 0.757), SAPS II (AUROC 0.759), OASIS (AUROC 0.742), SIRS (AUROC 0.638), and GAS (AUROC 0.586) systems. The results of the univariate and multivariate logistic analyses showed that SAPS III was statistically significant for both 28-day and 1-year mortality. Subgroup analyses yielded results consistent with the overall findings. No nonlinear relationship was identified between these scoring systems and 28-day all-cause mortality (P for nonlinear > 0.05)., Conclusion: The SAPS III system demonstrated superior discriminatory ability for both 28-day and 1-year mortality compared to the GAS, SAPS II SIRS, SOFA, and OASIS systems among patients with AA., (© 2024. The Author(s).)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients' symptoms cannot be relieved., Case Report: This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel., Results: After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations., Conclusion: Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids., (© 2024. The Author(s).)

Purpose: The survival rate of patients with medullary thyroid carcinoma (MTC) who fail to achieve a biochemical cure after surgery is reduced. This study aimed to investigate the prognostic factors affecting the survival of MTC patients who do not achieve a biochemical cure after surgery., Methods: Cox univariate and multivariate proportional hazard models were used to determine the influence of different variables on overall survival (OS). Pearson's chi-square test was used for categorical variables, and paired t-test was used for continuous variables., Results: In our study of 277 MTC patients treated between 2012 and 2022, there were 96 with raised postoperative 1-month calcitonin (Ct) levels (0-9.52 pg/ml). The overall survival (OS) rates of patients with high postoperative 1-month Ct values at 1, 3, and 5 years were 97.9%, 94.6%, and 86.8%, respectively. The univariate analysis revealed that patients with a postoperative 1-month Ct > 441.9 pg/ml had a greater risk of mortality than patients with postoperative 1-month Ct values ranging from 9.52 to 73.4 pg/ml (p = 0.043). Subsequent analyses revealed that receiving targeted therapy did not improve the OS of patients with distant metastasis among those with high postoperative 1-month Ct values (p = 0.527)., Conclusion: This study confirmed that MTC patients who did not achieve biochemical remission after surgery had an increased risk of death when the Ct level was > 441.9 pg/ml 1 month after surgery. Additionally, for MTC patients who have not achieved biochemical remission and have experienced disease progression or distant metastasis after surgery, the use of targeted therapy does not prolong survival., (© 2024. The Author(s).)

Background: Owing to a lack of data, this study aimed to explore the effect of cardiac preload on myocardial strain in patients with sepsis., Methods: A total of 70 patients with sepsis in intensive care unit (ICU) of a tertiary teaching hospital in China from January 2018 to July 2019 and underwent transthoracic echocardiography were enrolled. Echocardiographic data were recorded at ICU admission and 24 h later. Patients were assigned to low left ventricular end-diastolic volume index (LVEDVI) and normal LVEDVI groups. We assessed the impact of preload on myocardial strain between the groups and analyzed the correlation of echocardiographic parameters under different preload conditions., Results: Thirty-seven patients (53%) had a low LVEDVI and 33 (47%) a normal LVEDVI. Those in the low LVEDVI group had a faster heart rate (121.7 vs. 95.3, p < 0.001) and required a greater degree of fluid infusion (3.67 L vs. 2.62 L, P = 0.019). The left ventricular global strain (LVGLS) (-8.60% vs. -10.80%, p = 0.001), left ventricular global circumferential strain (LVGCS) (-13.83% vs. -18.26%, p = 0.006), and right ventricular global longitudinal strain (RVGLS) (-6.9% vs. -10.60%, p = 0.001) showed significant improvements in the low LVEDVI group after fluid resuscitation. However, fluid resuscitation resulted in a significantly increased cardiac afterload value (1172.00 vs. 1487.00, p = 0.009) only in the normal LVEDVI group. Multivariate backward linear regression showed that LVEDVI changes were independently associated with myocardial strain-related improvements during fluid resuscitation. The baseline LVEDVI was significantly negatively correlated with the LVGLS and RVGLS (r = -0.44 and - 0.39, respectively) but not LVGCS. LVEDVI increases during fluid resuscitation were associated with improvements in the myocardial strain degree., Conclusions: Myocardial strain alterations were significantly influenced by the cardiac preload during fluid resuscitation in sepsis., (© 2024. The Author(s).)

The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N 1 -(4-boronobenzyl)-N 3 -(4-boronophenyl)-N 1 , N 1 , N 3 , N 3 -teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation., (© 2024. The Author(s).)

Background: Diabetic wounds present significant challenges, specifically in terms of bacterial infection and delayed healing. Therefore, it is crucial to address local bacterial issues and promote accelerated wound healing. In this investigation, we utilized electrospinning to fabricate microgel/nanofiber membranes encapsulating MXene-encapsulated microgels and chitosan/gelatin polymers., Results: The film dressing facilitates programmed photothermal therapy (PPT) and mild photothermal therapy (MPTT) under near-infrared (NIR), showcasing swift and extensive antibacterial and biofilm-disrupting capabilities. The PPT effect achieves prompt sterilization within 5 min at 52 °C and disperses mature biofilm within 10 min. Concurrently, by adjusting the NIR power to induce local mild heating (42 °C), the dressing stimulates fibroblast proliferation and migration, significantly enhancing vascularization. Moreover, in vivo experimentation successfully validates the film dressing, underscoring its immense potential in addressing the intricacies of diabetic wounds., Conclusions: The MXene microgel-loaded nanofiber dressing employs temperature-coordinated photothermal therapy, effectively amalgamating the advantageous features of high-temperature sterilization and low-temperature promotion of wound healing. It exhibits rapid, broad-spectrum antibacterial and biofilm-disrupting capabilities, exceptional biocompatibility, and noteworthy effects on promoting cell proliferation and vascularization. These results affirm the efficacy of our nanofiber dressing, highlighting its significant potential in addressing the challenge of diabetic wounds struggling to heal due to infection., (© 2024. The Author(s).)

Background: Carotid endarterectomy (CEA) is a surgical procedure that can reduce the risk of stroke in patients with carotid artery stenosis. However, controversy still exists regarding the optimal surgical technique for CEA., Objective: To compare the safety and effectiveness of different techniques., Methods: Data on baseline characteristics as well as perioperative and postoperative complications from patients who underwent CEA at the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, were retrospectively collected and analyzed., Results: A total of 262 CEA patients included in study, with a total of 265 CEA operations. The mean age of 69.95 ± 7.29 (range, 44-89) years. 65 (24.5%) patients underwent cCEA, 94 (35.5%) underwent pCEA, and 106 (40.0%) underwent eCEA. The use of shunt (1.9%) and the mean operation time were lower in eCEA group (P < 0.05). eCEA was also associated with a lower incidence of postoperative hypotension, whereas pCEA was associated with a lower incidence of postoperative hypertension (P < 0.05). There was no significant difference in clinical baseline characteristics, occurrence of perioperative complications, and survival whether restenosis-free, asymptomatic or overall., Conclusions: This study found that all three surgical methods are equally safe for the treatment of carotid artery stenosis and are effective in preventing stroke., (© 2024. The Author(s).)

Background: Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology., Methods: On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers., Results: As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences., Conclusions: Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence., (© 2024. The Author(s).)

Background: Artificial intelligence is a growing phenomenon that will soon facilitate wide-scale changes in many professions, and is expected to play an important role in the field of medical education. This study explored the realistic feelings and experiences of nursing undergraduates participating in different stages of artificial intelligence + project task driven learning, and provide a basis for artificial intelligence participation in nursing teaching., Methods: We conducted face-to-face semi-structured interviews with nursing undergraduates participating in Nursing Research Course which adopts artificial intelligence + project task driven learning from a medical university in Ningxia from September to November 2023, to understand their experience of using artificial intelligence for learning and the emotional changes at different stages. The interview guide included items about their personal experience and feelings of completing project tasks through dialogue with artificial intelligence, and suggestions for course content. Thematic analysis was used to analyze interview data. This study followed the COREQ checklist., Results: According to the interview data, three themes were summarized. Undergraduate nursing students have different experiences in participating in artificial intelligence + project task driven learning at different stages, mainly manifested as diverse emotional experiences under initial knowledge deficiency, the individual growth supported by external forces during the adaptation period, and the expectations and suggestions after the birth of the results in the end period., Conclusions: Nursing undergraduates can actively adapt to the integration of artificial intelligence into nursing teaching, dynamically observe students' learning experience, strengthen positive guidance, and provide support for personalized teaching models, better leveraging the advantages of artificial intelligence participation in teaching., (© 2024. The Author(s).)

Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds., (© 2024. The Author(s).)

Background: Diabetic cardiomyopathy (DCM) is a crucial complication of long-term chronic diabetes that can lead to myocardial hypertrophy, myocardial fibrosis, and heart failure. There is increasing evidence that DCM is associated with pyroptosis, a form of inflammation-related programmed cell death. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily, which regulates oxidative stress, inflammation, and cell survival to mitigate myocardial hypertrophy, myocardial infarction, and vascular injury. However, the role of GDF11 in regulating pyroptosis in DCM remains to be elucidated. This research aims to investigate the role of GDF11 in regulating pyroptosis in DCM and the related mechanism., Methods and Results: Mice were injected with streptozotocin (STZ) to induce a diabetes model. H9c2 cardiomyocytes were cultured in high glucose (50 mM) to establish an in vitro model of diabetes. C57BL/6J mice were preinjected with adeno-associated virus 9 (AAV9) intravenously via the tail vein to specifically overexpress myocardial GDF11. GDF11 attenuated pyroptosis in H9c2 cardiomyocytes after high-glucose treatment. In diabetic mice, GDF11 alleviated cardiomyocyte pyroptosis, reduced myocardial fibrosis, and improved cardiac function. Mechanistically, GDF11 inhibited pyroptosis by preventing inflammasome activation. GDF11 achieved this by specifically binding to apoptosis-associated speck-like protein containing a CARD (ASC) and preventing the assembly and activation of the inflammasome. Additionally, the expression of GDF11 during pyroptosis was regulated by peroxisome proliferator-activated receptor α (PPARα)., Conclusion: These findings demonstrate that GDF11 can treat diabetic cardiomyopathy by alleviating pyroptosis and reveal the role of the PPARα-GDF11-ASC pathway in DCM, providing ideas for new strategies for cardioprotection., (© 2024. The Author(s).)

Objective: This study aims to establish and validate a nomogram model for the all-cause mortality rate in patients with diabetic nephropathy (DN)., Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. A random split of 7:3 was performed between the training and validation sets. Utilizing follow-up data until December 31, 2019, we examined the all-cause mortality rate. Cox regression models and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were employed in the training cohort to develop a nomogram for predicting all-cause mortality in the studied population. Finally, various validation methods were employed to assess the predictive performance of the nomogram, and Decision Curve Analysis (DCA) was conducted to evaluate the clinical utility of the nomogram., Results: After the results of LASSO regression models and Cox multivariate analyses, a total of 8 variables were selected, gender, age, poverty income ratio, heart failure, body mass index, albumin, blood urea nitrogen and serum uric acid. A nomogram model was built based on these predictors. The C-index values in training cohort of 3-year, 5-year, 10-year mortality rates were 0.820, 0.807, and 0.798. In the validation cohort, the C-index values of 3-year, 5-year, 10-year mortality rates were 0.773, 0.788, and 0.817, respectively. The calibration curve demonstrates satisfactory consistency between the two cohorts., Conclusion: The newly developed nomogram proves to be effective in predicting the all-cause mortality risk in patients with diabetic nephropathy, and it has undergone robust internal validation., (© 2024. The Author(s).)

Background: Previous observational research showed a potential link between physical activities such as walking and the risk of lung cancer. However, Mendelian randomization (MR) studies suggested there was no association between moderate to vigorous physical activity and lung cancer risk. We speculated that specific physical activities may be associated with lung cancer risk. Consequently, we conducted an MR study to examine the potential relationship between walking and the risk of lung cancer., Methods: We collected genetic summary data from UK Biobank. After excluding SNPs with F values less than 10 and those associated with confounding factors, we conducted a MR analysis to assess the causal effects between different types of walk and lung cancer. We also performed sensitivity analysis to validate the robustness of our findings. Finally, we analyzed the possible mediators., Results: MR analysis showed number of days/week walked for 10 + minutes was associated with a reduced risk of lung cancer risk (OR = 0.993, 95% CI = 0.987-0.998, P = 0.009). Additionally, usual walking pace was identified as a potentially significant factor in lowering the risk (OR = 0.989, 95% CI = 0.980-0.998, P = 0.015). However, duration of walks alone did not show a significant association with lung cancer risk (OR = 0.991, 95%CI = 0.977-1.005, P = 0.216). The sensitivity analysis confirmed the robustness of these findings. And number of days/week walked for 10 + minutes could affect fed-up feelings and then lung cancer risk. There was a bidirectional relationship between usual walking pace and sedentary behaviors (time spent watching TV)., Conclusion: The study unveiled a genetically predicted causal relationship between number of days/week walked for 10 + minutes, usual walking pace, and the risk of lung cancer. The exploration of potential mediators of walking phenotypes and their impact on lung cancer risk suggests that specific physical activities may reduce the risk of lung cancer., (© 2024. The Author(s).)

Background: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations., Methods: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11 + 0 -13 + 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20 + 0 -24 + 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA., Results: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations., Conclusions: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA., (© 2024. The Author(s).)

Objective: Presently, no study has compared the clinical outcomes of minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) with bilateral decompression via the unilateral approach (BDUA) and Open-TLIF with bilateral decompression for degenerative lumbar diseases (DLD). We aimed to compare the clinical outcomes of through Mis-TLIF combined with BDUA and Open-TLIF with bilateral decompression for the treatment of DLD, and reported the learning curve of the procedure of MIS-TLIF with BDUA., Methods: We retrospectively analyzed the prospectively collected data of consecutive DLD patients in the two groups from January 2016 to January 2020., Results: The operative time (OT) was significantly longer in the Mis-TLIF group (n = 113) than in the Open-TLIF group (n = 135). The postoperative drainage volume (PDV) and length of stay (LOS) were significantly higher in the Open-TLIF group than in the Mis-TLIF group. Additionally, the complication rate was significantly higher in the Open-TLIF group than in the Mis-TLIF group (14.8% vs. 6.2%, P = 0.030), while there was no significant difference in the reoperation and adjacent segment disease rates between the two groups. There were no significant differences in back pain and leg pain Numerical Rating Scale (NRS) scores and Oswestry Disability Index (ODI) between the two groups preoperatively, at discharge, and 2 years postoperatively. Patients in both groups showed significant improvements in NRS scores and ODI scores after surgery. OT was negatively correlated with the number of surgeries performed (P < 0.001, r =  -0.43). The learning curve of Mis-TLIF with BDUA was steep, with OT tapered to steady state in 43 cases., Conclusion: Compared with Open-TLIF with bilateral decompression, Mis-TLIF with BDUA can achieve equivalent clinical outcomes, lower PDV and LOS, and lower complication rates. Although this procedure took longer, it could be a viable alternative for the treatment of DLD after a steep learning curve., (© 2024. The Author(s).)

Background: Chimeric antigen receptor (CAR) T cell therapy has shown remarkable responses in hematological malignancies with several approved products, but not in solid tumors. Patients suffer from limited response and tumor relapse due to low efficacy of CAR-T cells in the complicated and immunosuppressive tumor microenvironment. This clinical challenge has called for better CAR designs and combined strategies to improve CAR-T cell therapy against tumor changes., Methods: In this study, IL-15/IL-15Rα was inserted into the extracellular region of CAR targeting mesothelin. In-vitro cytotoxicity and cytokine production were detected by bioluminescence-based killing and ELISA respectively. In-vivo xenograft mice model was used to evaluate the anti-tumor effect of CAR-T cells. RNA-sequencing and online database analysis were used to identify new targets in residual gastric cancer cells after cytotoxicity assay. CAR-T cell functions were detected in vitro and in vivo after GLI Pathogenesis Related 1 (GLIPR1) knockdown in gastric cancer cells. Cell proliferation and migration of gastric cancer cells were detected by CCK-8 and scratch assay respectively after GLIPR1 were overexpressed or down-regulated., Results: CAR-T cells constructed with IL-15/IL-15Rα (CAR-ss-T) showed significantly improved CAR-T cell expansion, cytokine production and cytotoxicity, and resulted in superior tumor control compared to conventional CAR-T cells in gastric cancer. GLIPR1 was up-regulated after CAR-T treatment and survival was decreased in gastric cancer patients with high GLIPR1 expression. Overexpression of GLIPR1 inhibited cytotoxicity of conventional CAR-T but not CAR-ss-T cells. CAR-T treatment combined with GLIPR1 knockdown increased anti-tumor efficacy in vitro and in vivo., Conclusions: Our data demonstrated for the first time that this CAR structure design combined with GLIPR1 knockdown in gastric cancer improved CAR-T cell-mediated anti-tumor response., (© 2024. The Author(s).)

Background: Current studies have shown that longer observation time can improve neoplastic detection rate. This study aimed to clarify whether endoscopists with longer observation times can detect more focal lesions., Methods: Based on the mean examination time for Esophagogastroduodenoscopy (EGD) without biopsy, endoscopists were divided into fast and slow groups, and the detection rate of focal lesions was compared between the two groups. Univariate analysis, multivariate analysis and restricted cubic spline were used to explore the factors of focal lesion detection rate., Results: Mean examination time of EGD without biopsy was 4.5 min. The cut-off times used were 5 min. 17 endoscopists were classified into the fast (4.7 ± 3.6 min), and 16 into the slow (7.11 ± 4.6 min) groups. Compared with fast endoscopists, slow endoscopists had a higher detection rate of focal lesions (47.2% vs. 51.4%, P < 0.001), especially in the detection of gastric lesions (29.7% vs. 35.9%, P < 0.001). In univariate and multivariate analyses, observation time, patient age and gender, expert, biopsy rate, and number of images were factors in FDR. There is a nonlinear relationship between observation time and FDR., Conclusion: Longer examination time improves the detection rate of focal lesions. Observation time is an important quality indicator of the EGD examination., (© 2024. The Author(s).)

Background: Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression., Methods: A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26)., Results: Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009)., Conclusions: Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated., Methods: The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2., Results: ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/β-catenin pathway., Conclusion: ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/β-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC., (© 2024. The Author(s).)

Background: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient., Case Presentation: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders., Conclusions: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels., (© 2024. The Author(s).)

Background: Major depressive disorder (MDD) has a high incidence and an unknown mechanism. There are no objective and sensitive indicators for clinical diagnosis., Objective: This study explored specific electrophysiological indicators and their role in the clinical diagnosis of MDD using machine learning., Methods: Forty first-episode and drug-naïve patients with MDD and forty healthy controls (HCs) were recruited. EEG data were collected from all subjects in the resting state with eyes closed for 10 min. The severity of MDD was assessed by the Hamilton Depression Rating Scale (HAMD-17). Machine learning analysis was used to identify the patients with MDD., Results: Compared to the HC group, the relative power of the low delta and theta bands was significantly higher in the right occipital region, and the relative power of the alpha band in the entire posterior occipital region was significantly lower in the MDD group. In the MDD group, the alpha band scalp functional connectivity was overall lower, while the scalp functional connectivity in the gamma band was significantly higher than that in the HC group. In the feature set of the relative power of the ROI in each band, the highest accuracy of 88.2% was achieved using the KNN classifier while using PCA feature selection. In the explanatory model using SHAP values, the top-ranking influence feature is the relative power of the alpha band in the left parietal region., Conclusions: Our findings reveal that the abnormal EEG neural oscillations may reflect an imbalance of excitation, inhibition and hyperactivity in the cerebral cortex in first-episode and drug-naïve patients with MDD. The relative power of the alpha band in the left parietal region is expected to be an objective electrophysiological indicator of MDD., (© 2023. The Author(s).)

Background: Polyploid giant cancer cells (PGCCs), a specific type of cancer stem cells (CSCs), can be induced by hypoxic microenvironments, chemical reagents, radiotherapy, and Chinese herbal medicine. Moreover, PGCCs can produce daughter cells that undergo epithelial-mesenchymal transition, which leads to cancer recurrence and disseminated metastasis. Vimentin, a mesenchymal cell marker, is highly expressed in PGCCs and their daughter cells (PDCs) and drives migratory persistence. This study explored the molecular mechanisms by which vimentin synergistically regulates PGCCs to generate daughter cells with enhanced invasive and metastatic properties., Methods: Arsenic trioxide (ATO) was used to induce the formation of PGCCs in Hct116 and LoVo cells. Immunocytochemical and immunohistochemical assays were performed to determine the subcellular localization of vimentin. Cell function assays were performed to compare the invasive metastatic abilities of the PDCs and control cells. The molecular mechanisms underlying vimentin expression and nuclear translocation were investigated by real-time polymerase chain reaction, western blotting, cell function assays, cell transfection, co-immunoprecipitation, and chromatin immunoprecipitation, followed by sequencing. Finally, animal xenograft experiments and clinical colorectal cancer samples were used to study vimentin expression in tumor tissues., Results: Daughter cells derived from PGCCs showed strong proliferative, migratory, and invasive abilities, in which vimentin was highly expressed and located in both the cytoplasm and nucleus. Vimentin undergoes small ubiquitin-like modification (SUMOylation) by interacting with SUMO1 and SUMO2/3, which are associated with nuclear translocation. P62 regulates nuclear translocation of vimentin by controlling SUMO1 and SUMO2/3 expression. In the nucleus, vimentin acts as a transcription factor that regulates CDC42, cathepsin B, and cathepsin D to promote PDC invasion and migration. Furthermore, animal experiments and human colorectal cancer specimens have confirmed the nuclear translocation of vimentin., Conclusion: P62-dependent SUMOylation of vimentin plays an important role in PDC migration and invasion. Vimentin nuclear translocation and overexpressed P62 of cancer cells may be used to predict patient prognosis, and targeting vimentin nuclear translocation may be a promising therapeutic strategy for metastatic cancers., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Ketamine and its enantiomer have rapid and robust effects on depressive symptom and suicidal ideation. Little is known about their cognitive effects in adolescents. We aimed to evaluate the short-term effect of esketamine on cognition in adolescents with major depressive disorder (MDD) and suicidal ideation., Method: In this randomized-controlled trial, 51 participants aged 13-18 with MDD and suicidal ideation received three intravenous infusions of either esketamine (0.25 mg/kg) or midazolam (0.02 mg/kg). Four dimensions of the MATRICS Consensus Cognitive Battery (MCCB), including processing speed, working memory, verbal learning and visual learning, were assessed at Days 0, 6 and 12., Results: In the linear mixed model, a significant time main effect (F = 12.803, P < 0.001), drug main effect (F = 6.607, P = 0.013), and interaction effect (F = 3.315, P = 0.041) was found in processing speed. Other dimensions including working memory and verbal learning showed significant time main effect (all P < 0.05), but no significant drug or interaction effect (all P > 0.05). Esketamine group showed improvement in processing speed from baseline to Days 6 and 12, and working memory from baseline to Day 12 (all P < 0.05). The generalized estimation equation showed no significant association between baseline cognition and antidepressant or antisuicidal effect (both P > 0.05)., Conclusions: The present study suggested that three-dose subanesthetic esketamine infusions did not harm cognition among adolescents with MDD and suicidal ideation. Instead, esketamine may be associated with improvement in processing speed., Trial Registration: This trial was registered in the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2000041232)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: 17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown., Methods: In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro., Results: sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression., Conclusion: These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Chronic kidney disease (CKD) is a global public health concern. Therefore, to provide timely intervention for non-hospitalized high-risk patients and rationally allocate limited clinical resources is important to mine the key factors when designing a CKD prediction model., Methods: This study included data from 1,358 patients with CKD pathologically confirmed during the period from December 2017 to September 2020 at Zhongshan Hospital. A CKD prediction interpretation framework based on machine learning was proposed. From among 100 variables, 17 were selected for the model construction through a recursive feature elimination with logistic regression feature screening. Several machine learning classifiers, including extreme gradient boosting, gaussian-based naive bayes, a neural network, ridge regression, and linear model logistic regression (LR), were trained, and an ensemble model was developed to predict 24-hour urine protein. The detailed relationship between the risk of CKD progression and these predictors was determined using a global interpretation. A patient-specific analysis was conducted using a local interpretation., Results: The results showed that LR achieved the best performance, with an area under the curve (AUC) of 0.850 in a single machine learning model. The ensemble model constructed using the voting integration method further improved the AUC to 0.856. The major predictors of moderate-to-severe severity included lower levels of 25-OH-vitamin, albumin, transferrin in males, and higher levels of cystatin C., Conclusions: Compared with the clinical single kidney function evaluation indicators (eGFR, Scr), the machine learning model proposed in this study improved the prediction accuracy of CKD progression by 17.6% and 24.6%, respectively, and the AUC was improved by 0.250 and 0.236, respectively. Our framework can achieve a good predictive interpretation and provide effective clinical decision support., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To explore relevant clinical factors of level IIB and contralateral level VI lymph node metastasis and evaluate the safety of low-collar extended incision (LCEI) for lymph node dissection in level II for papillary thyroid carcinoma (PTC) with pN1b., Method: A retrospective analysis was performed on 218 patients with PTC with pN1b who were treated surgically in the Head and Neck Surgery Center of Sichuan Cancer Hospital from September 2021 to May 2022. Data on age, sex, body mass index (BMI), tumor location, maximum tumor diameter, multifocality, Braf gene, T staging, surgical incision style, and lymph node metastasis in each cervical subregion were collected. The chi-square test was used for comparative analysis of relevant factors. All statistical analyses were completed by SPSS 24 software., Result: Each subgroup on sex, age, BMI, multifocality, tumor location, extrathyroidal extension, Braf gene, and lymphatic metastasis in level III, level IV, and level V had no significant difference in the positive rate of lymph node metastasis in level IIB (P > 0.05). In contrast, patients with bilateral lateral cervical lymphatic metastasis were more likely to have level IIB lymphatic metastasis than those with unilateral lateral cervical lymphatic metastasis, with a statistically significant difference (P = 0.000). In addition, lymph node metastasis in level IIA was significantly associated with lymph node metastasis in level IIB (P = 0.001). After multivariate analysis, lymph node metastasis in level IIA was independently associated with lymph node metastasis in level IIB (P = 0.010). The LCEI group had a similar lymphatic metastasis number and lymphatic metastasis rate in both level IIA and level IIB as the L-shaped incision group (P > 0.05). There were 86 patients with ipsilateral central lymphatic metastasis (78.2%). Patients with contralateral central lymphatic metastasis accounted for 56.4%. The contralateral central lymphatic metastasis rate was not correlated with age, BMI, multifocality, tumor invasion, or ipsilateral central lymphatic metastasis, and there was no significant difference (P > 0.05). The contralateral central lymphatic metastasis in males was slightly higher than that in females, and the difference was statistically significant (68.2% vs. 48.5%, P = 0.041)., Conclusion: Lymphatic metastasis in level IIA was an independent predictor of lymphatic metastasis in level IIB. When bilateral lateral cervical lymphatic metastasis or lymph node metastasis of level IIA is found, lymph node dissection in level IIB is strongly recommended. When unilateral lateral cervical lymphatic metastasis and lymphatic metastasis in level IIA are negative, lymph node dissection in level IIB may be performed as appropriate on the premise of no damage to the accessory nerve. LCEI is safe and effective for lymph node dissection in level II. When the tumor is located in the unilateral lobe, attention should be given to contralateral central lymph node dissection because of the high lymphatic metastasis rate., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Lung cancer is a complex and heterogeneous disease characterized by abnormal growth and proliferation of lung cells. It is the leading cause of cancer-related deaths worldwide, accounting for approximately 18% of all cancer deaths. In recent years, targeted therapy has emerged as a promising approach to treat lung cancer, which involves the use of drugs that selectively target specific molecules or signaling pathways that are critical for the growth and survival of cancer cells. Liquid-liquid phase separation (LLPS) is a fundamental biological process that occurs when proteins and other biomolecules separate into distinct liquid phases in cells. LLPS is essential for various cellular functions, including the formation of membraneless organelles, the regulation of gene expression, and the response to stress and other stimuli. Recent studies have shown that LLPS plays a crucial role in targeted therapy of lung cancer, including the sequestration of oncogenic proteins and the development of LLPS-based drug delivery systems. Understanding the mechanisms of LLPS in these processes could provide insights into new therapeutic strategies to overcome drug resistance in lung cancer cells., (© 2023. Society of Chinese Bioscientists in America (SCBA).)

Purpose: To establish an early clinical diagnosis model based on the retinal vascular features associated with POI, supplying a non-invasive way for accurately and early predicted the risk of POI., Methods: A total of 78 women with spontaneous POI and 48 healthy women were recruited from the Affiliated Shenzhen Maternity & Child Healthcare Hospital in the study. Retinal characteristics were analyzed using an automated retinal image analysis system. Binary logistic regression was used to identify POI cases and develop predictive models., Results: Compared to the normal group, the POI group had larger central retinal artery equivalent (CRAE) (P = 0.006), central retinal vein equivalent (CRVE) (P = 0.001), index of venules asymmetry (Vasym) (P = 0.000); larger bifurcation angles of arterioles (Aangle) (P = 0.001), bifurcation coefficient of venule (BCV) (P = 0.001) and more obvious arteriovenous nipping (Nipping) (P = 0.005), but lower arteriole-to-venule ratio (AVR) (P = 0.012). In the POI group, the odds ratio (OR) of Vasym was 6.72e-32 (95% C.I. 4.62e-49-9.79e-15, P = 0.000), the OR of BCV was 5.66e-20 (95% C.I. 1.93e-34-.0000, P = 5.66e-20) and the OR of Nipping was 6.65e-06 (95% C.I. 6.33e-10-.0698, P = 0.012). Moreover, the area under the ROC curve for the binary logistic regression with retinal characteristics was 0.8582, and the fitting degree of regression models was 60.48% (Prob > chi-square = 0.6048)., Conclusion: This study demonstrated that retinal image analysis can provide useful information for POI identification and certain characteristics may help with early clinical diagnosis of POI., (© 2023. The Author(s).)

Background: Tubulointerstitial lesions play a pivotal role in the progression of IgA nephropathy (IgAN). Elevated N-acetyl-beta-D-glucosaminidase (NAG) in urine is released from damaged proximal tubular epithelial cells (PTEC) and may serve as a biomarker of renal progression in diseases with tubulointerstitial involvement., Methods: We evaluated the predictive value of urinary NAG (uNAG) for disease progression in 213 biopsy-proven primary IgAN patients from January 2018 to December 2019 at Zhongshan Hospital, Fudan University. We compared the results with those of serum cystatin C (sCysC)., Results: Increased uNAG and sCysC levels were associated with worse clinical and histological manifestations. Only uNAG level was independently associated with remission status after adjustment. Patients with high uNAG levels (> 22.32 U/g Cr) had a 4.32-fold greater risk of disease progression. The combination of baseline uNAG and clinical data may achieve satisfactory risk prediction in IgAN patients with relatively preserved renal function (eGFR ≥ 60 ml/min/1.73 m 2 , area under the curve [AUC] 0.760)., Conclusion: Our results suggest that uNAG is a promising biomarker for predicting IgAN remission status., (© 2023. The Author(s).)

Background: Epithelial ovarian cancer is the leading cause of death from gynecologic cancer, in which serous ovarian carcinoma (SOC) is the most common histological subtype. Although PARP inhibitors (PARPi) and antiangiogenics have been accepted as maintenance treatment in SOC, response to immunotherapy of SOC patients is limited., Methods: The source of transcriptomic data of SOC was from the Cancer Genome Atlas database and Gene Expression Omnibus. The abundance scores of mesenchymal stem cells (MSC scores) were estimated for each sample by xCell. Weighted correlation network analysis is correlated the significant genes with MSC scores. Based on prognostic risk model construction with Cox regression analysis, patients with SOC were divided into low- and high-risk groups. And distribution of immune cells, immunosuppressors and pro-angiogenic factors in different risk groups was achieved by single-sample gene set enrichment analysis. The risk model of MSC scores was further validated in datasets of immune checkpoint blockade and antiangiogenic therapy. In the experiment, the mRNA expression of prognostic genes related to MSC scores was detected by real-time polymerase chain reaction, while the protein level was evaluated by immunohistochemistry., Results: Three prognostic genes (PER1, AKAP12 and MMP17) were the constituents of risk model. Patients classified as high-risk exhibited worse prognosis, presented with an immunosuppressive phenotype, and demonstrated high micro-vessel density. Additionally, these patients were insensitive to immunotherapy and would achieve a longer overall survival with antiangiogenesis treatment. The validation experiments showed that the mRNA of PER1, AKAP12, and MMP17 was highly expressed in normal ovarian epithelial cells compared to SOC cell lines and there was a positive correlation between protein levels of PER1, AKAP12 and MMP17 and metastasis in human ovarian serous tumors., Conclusion: This prognostic model established on MSC scores can predict prognosis of patients and provide the guidance for patients receiving immunotherapy and molecular targeted therapy. Because the number of prognostic genes was fewer than other signatures of SOC, it will be easily accessible on clinic., (© 2023. The Author(s).)

Background: Overaccumulation of chloride (Cl) when plants suffer NaCl causes cell damage and death, and is regulated by Cl - channel protein (CLC). Apple roots are very sensitive to Cl - , but information associated with CLC is limited in apple crop that widely cultivated in the world., Results: We identified 9 CLCs from the apple genome and divided them into two subclasses. Among them, MdCLC-c1 promoter contained the largest number of cis-acting elements associated with NaCl stress, and only the MdCLC-c1, MdCLC-d, and MdCLC-g were predicted that may be Cl - antiporters or channels. Expression analysis of MdCLCs homologs in the roots of Malus hupehensis showed that most of the MhCLCs expression were response to NaCl stress, especially MhCLC-c1 expression was upregulated continuously and rapidly expressed during NaCl treatment. Therefore, we isolated MhCLC-c1 and observed it was a plasma membrane-localized protein. The MhCLC-c1 suppression significantly increased sensitivity, reactive oxygen species content, and cell death of apple calli; while MhCLC-c1 overexpression decreased sensitivity, reactive oxygen species content, and cell death of apple calli and Arabidopsis by inhibiting intracellular Cl - accumulation under NaCl stress., Conclusions: The study selected and isolated a CLC-c gene MhCLC-c1 from Malus hupehensis based on identification of CLCs gene family in apple, and their homologs MhCLCs expression patterns during NaCl treatments, revealing that MhCLC-c1 alleviates NaCl-induced cell death by inhibiting intracellular Cl - accumulation. Our findings confer the comprehensive and in-depth upstanding of the mechanism that plants resist salt stress, and might also confer genetic improvement of salt tolerance in horticultural crops and the development and utilization of saline-alkali land., (© 2023. The Author(s).)

Background: Transcranial magnetic stimulation (TMS) is increasingly used as a promising non-pharmacological treatment for Parkinson's disease (PD). Scalp-to-cortex distance (SCD), as a key technical parameter of TMS, plays a critical role in determining the locations of treatment targets and corresponding dosage. Due to the discrepancies in TMS protocols, the optimal targets and head models have yet to be established in PD patients., Objective: To investigate the SCDs of the most popular used targets in left dorsolateral prefrontal cortex (DLPFC) and quantify its impact on the TMS-induced electric fields (E-fields) in early-stage PD patients., Methods: Structural magnetic resonance imaging scans from PD patients (n = 47) and normal controls (n = 36) were drawn from the NEUROCON and Tao Wu datasets. SCD of left DLPFC was measured by Euclidean Distance in TMS Navigation system. The intensity and focality of SCD-dependent E-fields were examined and quantified using Finite Element Method., Results: Early-stage PD patients showed an increased SCDs, higher variances in the SCDs and SCD-dependent E-fields across the seven targets of left DLPFC than normal controls. The stimulation targets located on gyral crown had more focal and homogeneous E-fields. The SCD of left DLPFC had a better performance in differentiating early-stage PD patients than global cognition and other brain measures., Conclusion: SCD and SCD-dependent E-fields could determine the optimal TMS treatment targets and may also be used as a novel marker to differentiate early-stage PD patients. Our findings have important implications for developing optimal TMS protocols and personalized dosimetry in real-world clinical practice., (© 2023. The Author(s).)

Background: Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSC ATV -EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSC ATV -EV., Methods: MSC ATV -EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSC ATV -EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo., Results: MSC ATV -EV significantly reduced the amount of CD68 + total macrophages and increased CD206 + M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P < 0.01-0.0001). On day 28, MSC ATV -EV much more significantly improved the cardiac function than MSC-EV with the infarct size markedly reduced (P < 0.05-0.0001). In vitro, MSC ATV -EV also significantly reduced the protein and mRNA expressions of M1 markers but increased those of M2 markers in lipopolysaccharide-treated macrophages (P < 0.05-0.0001). EV miR-139-3p was identified as a potential cardiac repair factor mediating macrophage polarization. Knockdown of miR-139-3p in MSC ATV -EV significantly attenuated while overexpression of it in MSC-EV enhanced the effect on promoting M2 polarization by suppressing downstream signal transducer and activator of transcription 1 (Stat1). Furthermore, MSC ATV -EV loaded with miR-139-3p inhibitors decreased while MSC-EV loaded with miR-139-3p mimics increased the expressions of M2 markers and cardioprotective efficacy., Conclusions: We uncovered a novel mechanism that MSC ATV -EV remarkably facilitate cardiac repair in AMI by promoting macrophage polarization via miR-139-3p/Stat1 pathway, which has the great potential for clinical translation., (© 2023. The Author(s).)

Background: Trouble sleeping is one of the major health issues nowadays. Current evidence on the correlation between muscle quality and trouble sleeping is limited., Methods: A cross-sectional study design was applied and participants aged from 18 to 60 years in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 was used for analysis. Muscle quality index (MQI) was quantitatively calculated as handgrip strength (HGS, kg) sum/ arm and appendicular skeletal muscle mass (ASM, kg) by using the sum of the non-dominant hand and dominant hand. Sleeping data was obtained by interviews and self-reported by individuals. The main analyses utilized weighted multivariable logistic regression models according to the complex multi-stage sampling design of NHANES. Restricted cubic spline model was applied to explore the non-linear relationship between MQI and trouble sleeping. Moreover, subgroup analyses concerning sociodemographic and lifestyle factors were conducted in this study., Results: 5143 participants were finally included in. In the fully adjusted model, an increased level of MQI was significantly associated with a lower odds ratio of trouble sleeping, with OR = 0.765, 95% CI: (0.652,0.896), p = 0.011. Restricted cubic spline showed a non-linear association between MQI and trouble sleeping. However, it seemed that the prevalence of trouble sleeping decreased with increasing MQI until it reached 2.362, after which the odds ratio of trouble sleeping reached a plateau. Subgroup analyses further confirmed that the negative association between the MQI and trouble sleeping was consistent and robust across groups., Conclusion: Overall, this study revealed that MQI can be used as a reliable predictor in odds ratio of trouble sleeping. Maintaining a certain level of muscle mass would be beneficial to sleep health. However, this was a cross-sectional study, and causal inference between MQI and trouble sleeping was worthy of further exploration., (© 2023. The Author(s).)

Gap junctions (GJs), which are composed of connexins (Cxs), provide channels for direct information exchange between cells. Cx expression has a strong spatial specificity; however, its influence on cell behavior and information exchange between cells cannot be ignored. A variety of factors in organisms can modulate Cxs and subsequently trigger a series of responses that have important effects on cellular behavior. The expression and function of Cxs and the number and function of GJs are in dynamic change. Cxs have been characterized as tumor suppressors in the past, but recent studies have highlighted the critical roles of Cxs and GJs in cancer pathogenesis. The complex mechanism underlying Cx and GJ involvement in cancer development is a major obstacle to the evolution of therapy targeting Cxs. In this paper, we review the post-translational modifications of Cxs, the interactions of Cxs with several chaperone proteins, and the effects of Cxs and GJs on cancer. Video Abstract., (© 2023. The Author(s).)

Background: Prolonged mechanical ventilation (PMV), mostly defined as mechanical ventilation > 72 h after lung transplantation with or without tracheostomy, is associated with increased mortality. Nevertheless, the predictive factors of PMV after lung transplant remain unclear. The present study aimed to develop a novel scoring system to identify PMV after lung transplantation., Methods: A total of 141 patients who underwent lung transplantation were investigated in this study. The patients were divided into PMV and non-prolonged ventilation (NPMV) groups. Univariate and multivariate logistic regression analyses were performed to assess factors associated with PMV. A risk nomogram was then established based on the multivariate analysis, and model performance was further examined regarding its calibration, discrimination, and clinical usefulness., Results: Eight factors were finally identified to be significantly associated with PMV by the multivariate analysis and therefore were included as risk factors in the nomogram as follows: the body mass index (BMI, P = 0.036); primary diagnosis as idiopathic pulmonary fibrosis (IPF, P = 0.038); pulmonary hypertension (PAH, P = 0.034); primary graft dysfunction grading (PGD, P = 0.011) at T 0 ; cold ischemia time (CIT P = 0.012); and three ventilation parameters (peak inspiratory pressure [PIP, P < 0.001], dynamic compliance [Cdyn, P = 0.001], and P/F ratio [P = 0.015]) at T 0 . The nomogram exhibited superior discrimination ability with an area under the curve of 0.895. Furthermore, both calibration curve and decision-curve analysis indicated satisfactory performance., Conclusion: A novel nomogram to predict individual risk of receiving PMV for patients after lung transplantation was established, which may guide preventative measures for tackling this adverse event., (© 2023. The Author(s).)

Background: Major depressive disorder (MDD) is a high risk factor for suicide, with up to 20% of MDD patients attempting suicide during their lifetime. Current treatments for MDD are slow onset of action, low efficiency, and the inability to control suicidal behaviors quickly and effectively. Intravenous ketamine has been shown to have a rapid but transient antidepressant effect, but there is still lack evidence on the efficacy and safety of intravenous esketamine in reducing suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. We designed a study to investigate the effect of short-term repeated intravenous infusion of esketamine three times in MDD patients with suicidal ideation., Methods: This study features a randomized, double-blind, placebo-controlled trial (RCT) comparing short-term repeated intravenous infusions of esketamine with placebo as a supplement to conventional antidepressants with an intervention period of 6 days and one infusion every other day, followed by 4 weeks of follow-up. These methods support the examination of the efficacy, safety, tolerability, and mechanism of action of short-term repeated intravenous infusions of esketamine in MDD patients with suicidal ideation., Discussion: This is the first RCT to explore the efficacy and safety of short-term repeated infusion of esketamine on suicidal ideation and depressive symptoms in MDD patients with suicidal ideation. If proven effective and tolerated, it will provide evidence for rapid and effective treatment of suicidal ideation and depressive symptoms in MDD individuals with suicidal ideation., Trial Registration: Chinese Clinical Trial Register, ChiCTR2000041232 . Registered 22 December 2020., (© 2022. The Author(s).)

Background: At present, chronic respiratory diseases are a major burden in terms of morbidity and mortality and are of increasing public health concern in China. Meanwhile, the prevalence of diabetes has increased by more than 10 times over the last 40 years. While a few studies have investigated the association between chronic respiratory diseases and diabetes mellitus, the association is not clear. This study aimed to explore this association and provide evidence., Methods: In this single-center study, we enrolled participants aged ≥ 20 years undergoing at least two regular health check-ups from 2009 to 2019 at MJ Healthcare Center in Beijing. Each health check-up included physical examination, biochemical tests, a pulmonary function test, a questionnaire. A total of 11,107 adults were included, and cross-sectional and longitudinal analyses were performed., Results: We found that both prediabetic and diabetic adults had lower lung function than the normal population at baseline, indicating that lung function decline may start from prediabetic status. Quantitatively, with 1-mmol/L increase in fasting plasma glucose level, the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 ), FVC% and FEV 1 % lowered by 25 ml, 13 ml, 0.71-1.03%, and 0.46-0.72%, respectively. However, no significant difference was found in the rates for the lung function decline among different baseline diabetes statuses., Conclusion: People with higher blood glucose level had more severe lung function decline, with decline starting from prediabetic status, but no significant difference was noted in the rate of lung function decline based on different baseline diabetic statuses., (© 2022. The Author(s).)

Background: Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning-based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes., Methods: The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%., Results: This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models., Conclusion: AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data., (© 2022. The Author(s).)

Background: This study used the revised nursing outcomes classification (NOC) outlined in our previous study, "Core nursing outcomes for otorhinolaryngology head-neck," for telephone follow-up of patients who had laryngeal carcinoma surgery in China. This randomized controlled trial aimed to compare nurse-led telephone follow-up according to the revised NOC with traditional telephone follow-up., Methods: A total of 100 postoperative patients were recruited from March 2018‒March 2020. Patients were randomly assigned to nurse-led telephone follow-up groups as either revised NOC follow-up (n = 51) or traditional follow-up (n = 49). The investigated outcomes included nursing outcomes, quality of life, and self-care abilities., Results: The baseline characteristics of patients were well balanced. We noted that improvements in nursing outcomes in the intervention group were significantly better than for those in the control group (P = 0.018), primarily regarding psychosocial health (P < 0.001) and health knowledge and behavior (P < 0.001). Moreover, patient outcomes in the intervention group were associated with greater improvements in quality of life than those in the control group (P < 0.001), especially for social conditions (P < 0.001), emotional health (P < 0.001), functional status (P < 0.001), and additional attention (P = 0.001). Finally, compared with the control group, significant improvements were observed in self-care abilities in the intervention group (P = 0.002), mainly regarding general self-care abilities (P = 0.016) and development self-care abilities (P < 0.001)., Conclusion: This study found that nurse-led telephone follow-up according to the revised NOC improved nursing outcomes, quality of life, and self-care abilities., Trial Registration: ChiCTR2100045941., (© 2022. The Author(s).)

Background: N-acetyltransferase 10 (NAT10), an abundant nucleolar protein with both lysine and RNA cytidine acetyltransferase activities, has been implicated in Hutchinson-Gilford progeria syndrome and human cancer. We and others recently demonstrated that NAT10 is translocated from the nucleolus to the nucleoplasm after DNA damage, but the underlying mechanism remains unexplored., Methods: The NAT10 and PARP1 knockout (KO) cell lines were generated using CRISPR-Cas9 technology. Knockdown of PARP1 was performed using specific small interfering RNAs targeting PARP1. Cells were irradiated with γ-rays using a 137 Cs Gammacell-40 irradiator and subjected to clonogenic survival assays. Co-localization and interaction between NAT10 and MORC2 were examined by immunofluorescent staining and immunoprecipitation assays, respectively. PARylation of NAT10 and translocation of NAT10 were determined by in vitro PARylation assays and immunofluorescent staining, respectively., Results: Here, we provide the first evidence that NAT10 underwent covalent PARylation modification following DNA damage, and poly (ADP-ribose) polymerase 1 (PARP1) catalyzed PARylation of NAT10 on three conserved lysine (K) residues (K1016, K1017, and K1020) within its C-terminal nucleolar localization signal motif (residues 983-1025). Notably, mutation of those three PARylation residues on NAT10, pharmacological inhibition of PARP1 activity, or depletion of PARP1 impaired NAT10 nucleoplasmic translocation after DNA damage. Knockdown or inhibition of PARP1 or expression of a PARylation-deficient mutant NAT10 (K3A) attenuated the co-localization and interaction of NAT10 with MORC family CW-type zinc finger 2 (MORC2), a newly identified chromatin-remodeling enzyme involved in DNA damage response, resulting in a decrease in DNA damage-induced MORC2 acetylation at lysine 767. Consequently, expression of a PARylation-defective mutant NAT10 resulted in enhanced cellular sensitivity to DNA damage agents., Conclusion: Collectively, these findings indicate that PARP1-mediated PARylation of NAT10 is key for controlling its nucleoplasmic translocation and function in response to DNA damage. Moreover, our findings provide novel mechanistic insights into the sophisticated paradigm of the posttranslational modification-driven cellular response to DNA damage. Video Abstract., (© 2022. The Author(s).)

Background: Bone marrow cells (BMCs), especially mesenchymal stem cells (MSCs), have shown attractive application prospects in acute myocardial infarction (AMI). However, the weak efficacy becomes their main limitation in clinical translation. Based on the anti-inflammation and anti-apoptosis effects of a Chinese medicine-Tongxinluo (TXL), we aimed to explore the effects of TXL-pretreated MSCs (MSCs TXL ) in enhancing cardiac repair and further investigated the underlying mechanism., Methods: MSCs TXL or MSCs and the derived exosomes (MSCs TXL -exo or MSCs-exo) were collected and injected into the infarct zone of rat hearts. In vivo, the anti-apoptotic and anti-inflammation effects, and cardiac functional and histological recovery were evaluated. In vitro, the apoptosis was evaluated by western blotting and flow cytometry. miRNA sequencing was utilized to identify the significant differentially expressed miRNAs between MSCs TXL -exo and MSCs-exo, and the miRNA mimics and inhibitors were applied to explore the specific mechanism., Results: Compared to MSCs, MSCs TXL enhanced cardiac repair with reduced cardiomyocytes apoptosis and inflammation at the early stage of AMI and significantly improved left ventricular ejection fraction (LVEF) with reduced infarct size in an exosome-dependent way. Similarly, MSCs TXL -exo exerted superior therapeutic effects in anti-apoptosis and anti-inflammation, as well as improving LVEF and reducing infarct size compared to MSCs-exo. Further exosomal miRNA analysis demonstrated that miR-146a-5p was the candidate effector of the superior effects of MSCs TXL -exo. Besides, miR-146a-5p targeted and decreased IRAK1, which inhibited the nuclear translocation of NF-κB p65 thus protecting H9C2 cells from hypoxia injury., Conclusions: This study suggested that MSCs TXL markedly facilitated cardiac repair via a new mechanism of the exosomal transfer of miR-146a-5p targeting IRAK1/NF-κB p65 pathway, which has great potential for clinical translation., (© 2022. The Author(s).)

Background: Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments., Methods/design: This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes., Discussion: The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice., Systematic Review Registration: PROSPERO CRD4202123718., (© 2022. The Author(s).)

Objective: This study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets., Methods: Three transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein-protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks., Results: A total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors., Conclusions: We screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets., (© 2022. The Author(s).)