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1.
Cureus ; 16(4): e57592, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38707026

ABSTRACT

Panniculus morbidus (PM) is a presentation of severe chronic abdominal lymphoedema associated with obesity resulting in oedema and chronic fibrosis. It is a multifaceted condition with significant clinical and psychosocial implications. A 29-year-old female weighing 260 kg with a body mass index of 95 kg/m2 had recurrent infections and sepsis associated with an abdominal pannus extending to her knees and an area of ulceration. The pannus was indurated with extensive fibrosis that significantly affected her quality of life (QOL) requiring assistance for all activities of daily living (ADLs). A panniculectomy was performed with a negative pressure skin dressing over the skin wound. She was discharged after two days. Two months postoperatively, she reported significant improvement in QOL and can now mobilise and perform ADLs independently with no recurrent admissions. The global prevalence of obesity is reaching pandemic proportions and so will its complications. It can be functionally debilitating and worsen obesity. Surgical resection is indicated to restore mobility and function, prevent recurrent infections, improve QOL, and reduce economic burden. Patients report high satisfaction rates following surgery. Panniculectomy is an effective treatment to alleviate morbidity in severe obesity and should be considered in patients with recurrent infections and a significant impact on QOL.

2.
Sci Rep ; 14(1): 10577, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38719920

ABSTRACT

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20-40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159-1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.


Subject(s)
Erectile Dysfunction , Foot , Hand , Humans , Male , Erectile Dysfunction/epidemiology , Erectile Dysfunction/etiology , Taiwan/epidemiology , Adult , Cross-Sectional Studies , Young Adult , Hand/physiopathology , Foot/physiopathology , Cryopyrin-Associated Periodic Syndromes/epidemiology , Cryopyrin-Associated Periodic Syndromes/complications , Surveys and Questionnaires , Prevalence , Cold Temperature/adverse effects , Risk Factors
3.
Int J Biol Sci ; 20(7): 2476-2490, 2024.
Article in English | MEDLINE | ID: mdl-38725863

ABSTRACT

Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT)+ and vesicular glutamate transporter 2 (VGLUT2)+ but not inhibitory neuronal nitric oxide synthase (nNOS)+ neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT+ and VGLUT2+ neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT+ and VGLUT2+ neurons was dependent on the MMs. Gut microbiota metabolites ß-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.


Subject(s)
Homeostasis , Macrophages , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Neurons , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Mice , Macrophages/metabolism , Neurons/metabolism , Mice, Inbred C57BL , Male , Choline O-Acetyltransferase/metabolism , Choline O-Acetyltransferase/genetics , Gastrointestinal Motility/physiology , Gastrointestinal Microbiome/physiology
4.
Fitoterapia ; 176: 105985, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38705541

ABSTRACT

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

5.
Digit Health ; 10: 20552076241257014, 2024.
Article in English | MEDLINE | ID: mdl-38778867

ABSTRACT

Background: Vaginal birth after cesarean (VBAC) is generally regarded as a safe and viable birthing option for most women with prior cesarean delivery. Nonetheless, concerns about heightened risks of adverse maternal and perinatal outcomes have often dissuaded women from considering VBAC. This study aimed to assess the performance of an artificial intelligence (AI)-powered VBAC prediction system integrated into a decision-aid birth choice platform for shared decision-making (SDM). Materials and Methods: Employing a retrospective design, we collected medical records from a regional hospital in northern Taiwan from January 2019 to May 2023. To explore a suitable model for tabular data, we compared two prevailing modeling approaches: tree-based models and logistic regression models. We subjected the tree-based algorithm, CatBoost, to binary classification. Results: Forty pregnant women with 347 records were included. The CatBoost model demonstrated a robust performance, boasting an accuracy rate of 0.91 (95% confidence interval (CI): 0.86-0.94) and an area under the curve of 0.89 (95% CI: 0.86-0.93), surpassing both regression models and other boosting techniques. CatBoost captured the data characteristics on the significant impact of gravidity and the positive influence of previous vaginal birth, reinforcing established clinical guidelines, as substantiated by the SHapley Additive exPlanations analysis. Conclusion: Using AI techniques offers a more accurate assessment of VBAC risks, boosting women's confidence in selecting VBAC as a viable birthing option. The seamless integration of AI prediction systems with SDM platforms holds a promising potential for enhancing the effectiveness of clinical applications in the domain of women's healthcare.

6.
Cancer Lett ; 592: 216924, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38718886

ABSTRACT

Oncolytic viruses (OVs) represent an emerging immunotherapeutic strategy owing to their capacity for direct tumor lysis and induction of antitumor immunity. However, hurdles like transient persistence and moderate efficacy necessitate innovative approaches. Metabolic remodeling has recently gained prominence as a strategic intervention, wherein OVs or combination regimens could reprogram tumor and immune cell metabolism to enhance viral replication and oncolysis. In this review, we summarize recent advances in strategic reprogramming of tumor and immune cell metabolism to enhance OV-based immunotherapies. Specific tactics include engineering viruses to target glycolytic, glutaminolytic, and nucleotide synthesis pathways in cancer cells, boosting viral replication and tumor cell death. Additionally, rewiring T cell and NK cell metabolism of lipids, amino acids, and carbohydrates shows promise to enhance antitumor effects. Further insights are discussed to pave the way for the clinical implementation of metabolically enhanced oncolytic platforms, including balancing metabolic modulation to limit antiviral responses while promoting viral persistence and tumor clearance.


Subject(s)
Neoplasms , Oncolytic Virotherapy , Oncolytic Viruses , Humans , Oncolytic Virotherapy/methods , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/metabolism , Oncolytic Viruses/metabolism , Animals , Virus Replication , Immunotherapy/methods , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism
7.
Stroke ; 55(6): 1468-1476, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38747162

ABSTRACT

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.


Subject(s)
Endovascular Procedures , Ischemic Stroke , Humans , Male , Female , Middle Aged , Endovascular Procedures/methods , Aged , Ischemic Stroke/therapy , Hyperoxia , Treatment Outcome , Combined Modality Therapy , Oxygen Inhalation Therapy/methods
8.
BMC Cancer ; 24(1): 622, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778261

ABSTRACT

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bile Duct Neoplasms , Cholangiocarcinoma , Cost-Benefit Analysis , Fluorouracil , Glycine , Isocitrate Dehydrogenase , Leucovorin , Mutation , Pyridines , Humans , Isocitrate Dehydrogenase/genetics , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Pyridines/therapeutic use , Pyridines/economics , Taiwan , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/economics , Fluorouracil/therapeutic use , Fluorouracil/economics , Glycine/analogs & derivatives , Glycine/therapeutic use , Glycine/economics , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/economics , Leucovorin/therapeutic use , Leucovorin/economics , Male , Female , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/economics , Middle Aged
9.
Virulence ; 15(1): 2350892, 2024 12.
Article in English | MEDLINE | ID: mdl-38745370

ABSTRACT

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.


Subject(s)
Blood Platelets , Histocompatibility Antigens Class I , Killer Cells, Natural , Syphilis , Treponema pallidum , Killer Cells, Natural/immunology , Treponema pallidum/immunology , Treponema pallidum/genetics , Humans , Blood Platelets/immunology , Blood Platelets/microbiology , Histocompatibility Antigens Class I/immunology , Syphilis/immunology , Syphilis/microbiology , Immune Evasion
10.
J Dent Educ ; 88 Suppl 1: 685-689, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38758067

ABSTRACT

BACKGROUND: Women have made significant advancements in the dentist workforce, growing from 20% of dentists in 2005 to 34.5% in 2020. Women have also made inroads in academic dentistry. While much scholarship has documented a growing feminization in dentistry and efforts to promote gender equity in the profession, there has been less exploration of the intersectional identities of these women. This manuscript explores how academic dentistry can support diverse women's leadership focusing on intersectional identities. METHODS: Applying the theoretical framework of intersectionality, we assess publicly available data to explore the percentages of faculty and deans who are women of color. Drawing upon best practices in higher education and our personal experiences, we explore opportunities to increase participation and support the advancement of women of color in academia. RESULTS: In the academic year 2018-2019, of the 5066 full-time faculty members, 40.5% were women. Minoritized women comprised 13.4% of full-time faculty members, compared to White women who were 20.6% of full-time faculty. Minoritized women comprised 7.3% of dental school deans, compared to White women who were 17.6% of deans. CONCLUSION: Intersectionality allows for a deeper examination of women in academic dentistry. Women of color are often erased in discussions about women in academic dentistry, even as the profession celebrates the progress made by women. Embracing the intersectional identities of women and by extension, people who identify as gender non-confirming may help dental schools to become humanistic environments where faculty and leadership represent the growing diversity in the profession and in the world.


Subject(s)
Dentists, Women , Leadership , Humans , Female , Faculty, Dental , Gender Equity , Social Identification , United States , Cultural Diversity , Schools, Dental/organization & administration
11.
Article in English | MEDLINE | ID: mdl-38739153

ABSTRACT

INTRODUCTION: The choice between a cementless taper wedge stem and a fit-and-fill stem in total Hip arthroplasty (THA) for various proximal femoral morphological types has not been thoroughly evaluated. This study aimed to compare the risk of stem-related complications between these two stem types in Dorr type A, B, and C femurs. MATERIALS AND METHODS: From January 2015 through April 2021, we retrospectively reviewed 1995 cementless THA procedures. We stratified all procedures into three groups: Dorr type A (N = 360, 18.0%), B (N = 1489, 74.7%) and C (N = 146, 7.3%). The primary outcome domain was stem-related complications, including stem subsidence ≥ 3 mm, intraoperative fracture, periprosthetic fracture and aseptic stem loosening. We performed multivariate regression analysis to compare the risk of stem-related complication between the two stem types. Other factors included age, sex, body mass index, diagnosis, age-adjusted Charlson comorbidity index, stem alignment and canal fill ratio. RESULTS: The incidence of stem-related complications in the taper wedge and fit-and-fill stem groups was 4.4% (N = 15) and 6.5% (N = 107), respectively. Fit-and-fill stems showed an increased risk of stem-related complications (aOR: 9.903, 95% CI: 1.567-62.597) only in Dorr type C femurs. No significant difference in risk was observed in Dorr type A and B femurs. Furthermore, the canal fill ratio at the lesser trochanter, 2 cm and 7 cm below the lesser trochanter, did not exhibit an association with stem-related complications in any Dorr type. CONCLUSIONS: Concerning the risk of stem-related complications, the taper wedge stem was a better choice in Dorr type C femurs. However, there was no difference in risk between the taper wedge stem and fit-and-fill stem in Dorr type A and B femurs.

12.
PLoS One ; 19(5): e0299602, 2024.
Article in English | MEDLINE | ID: mdl-38696439

ABSTRACT

PURPOSE: The purposes of this study were to determine whether biomechanical properties of mature oocytes could predict usable blastocyst formation better than morphological information or maternal factors, and to demonstrate the safety of the aspiration measurement procedure used to determine the biomechanical properties of oocytes. METHODS: A prospective split cohort study was conducted with patients from two IVF clinics who underwent in vitro fertilization. Each patient's oocytes were randomly divided into a measurement group and a control group. The aspiration depth into a micropipette was measured, and the biomechanical properties were derived. Oocyte fertilization, day 3 morphology, and blastocyst development were observed and compared between measured and unmeasured cohorts. A predictive classifier was trained to predict usable blastocyst formation and compared to the predictions of four experienced embryologists. RESULTS: 68 patients and their corresponding 1252 oocytes were included in the study. In the safety analyses, there was no significant difference between the cohorts for fertilization, while the day 3 and 5 embryo development were not negatively affected. Four embryologists predicted usable blastocyst development based on oocyte morphology with an average accuracy of 44% while the predictive classifier achieved an accuracy of 71%. Retaining the variables necessary for normal fertilization, only data from successfully fertilized oocytes were used, resulting in a classifier an accuracy of 81%. CONCLUSIONS: To date, there is no standard guideline or technique to aid in the selection of oocytes that have a higher likelihood of developing into usable blastocysts, which are chosen for transfer or vitrification. This study provides a comprehensive workflow of extracting biomechanical properties and building a predictive classifier using these properties to predict mature oocytes' developmental potential. The classifier has greater accuracy in predicting the formation of usable blastocysts than the predictions provided by morphological information or maternal factors. The measurement procedure did not negatively affect embryo culture outcomes. While further analysis is necessary, this study shows the potential of using biomechanical properties of oocytes to predict embryo developmental outcomes.


Subject(s)
Blastocyst , Embryonic Development , Fertilization in Vitro , Oocytes , Humans , Blastocyst/physiology , Blastocyst/cytology , Female , Oocytes/physiology , Oocytes/cytology , Adult , Biomechanical Phenomena , Fertilization in Vitro/methods , Embryonic Development/physiology , Prospective Studies
14.
World J Clin Cases ; 12(14): 2359-2369, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38765736

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ArLD) constitute the primary forms of chronic liver disease, and their incidence is progressively increasing with changes in lifestyle habits. Earlier studies have documented a correlation between the occurrence and development of prevalent mental disorders and fatty liver. AIM: To investigate the correlation between fatty liver and mental disorders, thus necessitating the implementation of a mendelian randomization (MR) study to elucidate this association. METHODS: Data on NAFLD and ArLD were retrieved from the genome-wide association studies catalog, while information on mental disorders, including Alzheimer's disease, schizophrenia, anxiety disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder, multiple personality disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and schizophrenia was acquired from the psychiatric genomics consortium. A two-sample MR method was applied to investigate mediators in significant associations. RESULTS: After excluding weak instrumental variables, a causal relationship was identified between fatty liver disease and the occurrence and development of some psychiatric disorders. Specifically, the findings indicated that ArLD was associated with a significantly elevated risk of developing ADHD (OR: 5.81, 95%CI: 5.59-6.03, P < 0.01), bipolar disorder (OR: 5.73, 95%CI: 5.42-6.05, P = 0.03), OCD (OR: 6.42, 95%CI: 5.60-7.36, P < 0.01), and PTSD (OR: 5.66, 95%CI: 5.33-6.01, P < 0.01). Meanwhile, NAFLD significantly increased the risk of developing bipolar disorder (OR: 55.08, 95%CI: 3.59-845.51, P < 0.01), OCD (OR: 61.50, 95%CI: 6.69-565.45, P < 0.01), and PTSD (OR: 52.09, 95%CI: 4.24-639.32, P < 0.01). CONCLUSION: Associations were found between genetic predisposition to fatty liver disease and an increased risk of a broad range of psychiatric disorders, namely bipolar disorder, OCD, and PTSD, highlighting the significance of preventive measures against psychiatric disorders in patients with fatty liver disease.

15.
Mater Today Bio ; 26: 101058, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38681057

ABSTRACT

Biomechanical cues could effectively govern cell gene expression to direct the differentiation of specific stem cell lineage. Recently, the medium viscosity has emerged as a significant mechanical stimulator that regulates the cellular mechanical properties and various physiological functions. However, whether the medium viscosity can regulate the mechanical properties of human mesenchymal stem cells (hMSCs) to effectively trigger osteogenic differentiation remains uncertain. The mechanism by which cells sense and respond to changes in medium viscosity, and regulate cell mechanical properties to promote osteogenic lineage, remains elusive. In this study, we demonstrated that hMSCs, cultured in a high-viscosity medium, exhibited larger cell spreading area and higher intracellular tension, correlated with elevated formation of actin stress fibers and focal adhesion maturation. Furthermore, these changes observed in hMSCs were associated with activation of TRPV4 (transient receptor potential vanilloid sub-type 4) channels on the cell membrane. This feedback loop among TRPV4 activation, cell spreading and intracellular tension results in calcium influx, which subsequently promotes the nuclear localization of NFATc1 (nuclear factor of activated T cells 1). Concomitantly, the elevated intracellular tension induced nuclear deformation and promoted the nuclear localization of YAP (YES-associated protein). The concurrent activation of NFATc1 and YAP significantly enhanced alkaline phosphatase (ALP) for pre-osteogenic activity. Taken together, these findings provide a more comprehensive view of how viscosity-induced alterations in biomechanical properties of MSCs impact the expression of osteogenesis-related genes, and ultimately promote osteogenic lineage.

16.
World J Gastroenterol ; 30(15): 2128-2142, 2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38681988

ABSTRACT

BACKGROUND: The prognosis for hepatocellular carcinoma (HCC) in the presence of cirrhosis is unfavourable, primarily attributable to the high incidence of recurrence. AIM: To develop a machine learning model for predicting early recurrence (ER) of post-hepatectomy HCC in patients with cirrhosis and to stratify patients' overall survival (OS) based on the predicted risk of recurrence. METHODS: In this retrospective study, 214 HCC patients with cirrhosis who underwent curative hepatectomy were examined. Radiomics feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination methods. Clinical-radiologic features were selected through univariate and multivariate logistic regression analyses. Five machine learning methods were used for model comparison, aiming to identify the optimal model. The model's performance was evaluated using the receiver operating characteristic curve [area under the curve (AUC)], calibration, and decision curve analysis. Additionally, the Kaplan-Meier (K-M) curve was used to evaluate the stratification effect of the model on patient OS. RESULTS: Within this study, the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic features. In the training cohort, this model attained an AUC of 0.844, while in the validation cohort, it achieved a value of 0.790. The K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients' OS. CONCLUSION: The combined model, integrating both radiomics and clinical-radiologic characteristics, exhibited excellent performance in HCC with cirrhosis. The K-M curves assessing OS revealed statistically significant differences.


Subject(s)
Carcinoma, Hepatocellular , Hepatectomy , Liver Cirrhosis , Liver Neoplasms , Machine Learning , Neoplasm Recurrence, Local , Tomography, X-Ray Computed , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Female , Liver Cirrhosis/complications , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/surgery , Retrospective Studies , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Aged , Tomography, X-Ray Computed/methods , Prognosis , Predictive Value of Tests , ROC Curve , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Kaplan-Meier Estimate , Adult , Liver/diagnostic imaging , Liver/pathology , Liver/surgery , Risk Factors , Radiomics
17.
Sci Rep ; 14(1): 9891, 2024 04 30.
Article in English | MEDLINE | ID: mdl-38688919

ABSTRACT

To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.


Subject(s)
Kidney Calculi , Humans , Kidney Calculi/surgery , Male , Female , Middle Aged , Retrospective Studies , Adult , Aged , ROC Curve , Kidney/surgery , Kidney Pelvis/surgery , Tomography, X-Ray Computed
18.
J Med Food ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682284

ABSTRACT

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use.

19.
Kaohsiung J Med Sci ; 40(5): 445-455, 2024 May.
Article in English | MEDLINE | ID: mdl-38593276

ABSTRACT

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.


Subject(s)
Cell Movement , Proto-Oncogene Proteins c-akt , Receptor, trkC , Signal Transduction , Humans , Receptor, trkC/metabolism , Receptor, trkC/genetics , Female , Cell Line, Tumor , Male , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , Middle Aged , Aged , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/genetics , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositol 3-Kinases/genetics , Kaplan-Meier Estimate , Urologic Neoplasms/genetics , Urologic Neoplasms/metabolism , Urologic Neoplasms/pathology
20.
Medicine (Baltimore) ; 103(14): e37676, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38579079

ABSTRACT

This study aimed to investigate factors associated with the clinical outcomes of patients who underwent pediatric liver transplantation (LT) and received enhanced recovery after surgery (ERAS) nursing. A cohort of 104 pediatric patients was studied at our hospital. Data on 8 indicators and 2 clinical outcomes, including length of hospital stay (LOS) and 30-day readmission rates, were collected. Linear and logistic regression analyses were employed to examine the associations of the 8 indicators with hospital-LOS and readmission risks, respectively. The predictive value of these indicators for the outcomes was determined using the receiver operating characteristic (ROC) curve, decision curve analysis, and importance ranking through the XGBoost method. A comprehensive model was developed to evaluate its predictive accuracy. Regression analyses identified donor age, donor gender, and intensive care unit (ICU)-LOS of recipients as significant predictors of hospital LOS (all P < .05), whereas no indicators were significantly associated with readmission risk. Further, ROC analysis revealed that 3 indicators provided superior prediction for 28-day hospital LOS compared to the median LOS of 18 days. ICU-LOS demonstrated the highest clinical net benefit for predicting 28-day hospital-LOS. Multivariable regression analysis confirmed the independent predictive value of donor age and ICU-LOS for the hospital-LOS (all ß > 0, all P < .05). Although the comprehensive model incorporating donor age and ICU-LOS showed stable predictive capability for hospital-LOS, its performance did not significantly exceed that of the individual indicators. In pediatric LT, hospital LOS warrants greater emphasis over readmission rates. Donor age and ICU-LOS emerged as independent risk factors associated with prolonged hospital LOS.


Subject(s)
Enhanced Recovery After Surgery , Liver Transplantation , Humans , Child , Prognosis , Risk Factors , Intensive Care Units , Length of Stay , Retrospective Studies
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