International Journal of Medical Sciences最新文献

Background: A more accurate assessment of extrahepatic metastases (EHMs) with colorectal cancer liver metastases (CRLMs) improve patient prognosis without unnecessary surgery and economic burden. At present, PET-CT can only be used as a second-line modality. We aimed to construct a predictive model for EHMs, and provide guidance for the selective application of ¹⁸F-FDG PET/CT. Methods: The clinical data of patients with CRLMs between December 2018 and February 2023 were retrospectively retrieved from the medical records of three large-capacity hospitals. Moreover, we explored the need for ¹⁸F-FDG PET/CT to be used selectively for detecting EHMs with CRLMs. Results: A total of 471 patients from two hospitals were included in the training set, 174 of whom had CRLMs and EHMs. Notably, the percentages of patients with positive serum CEA, CA19-9 and CA-125 levels were significantly greater in patients with CRLMs and EHMs than in those with liver-limited metastases. Univariate and multivariate logistic regression analyses revealed that the serum levels of CEA and CA-125 and multiple liver metastases were independent risk factors for EHMs. Additionally, we recruited 190 patients with CRLMs from one of the hospitals as the validation set. The nomogram model achieved stable and accurate prediction results in the training and validation sets (AUC = 0.768 and 0.733), and was significantly superior to CEA and CA19-9. Moreover, the sensitivity and specificity of ¹⁸F-FDG PET/CT for the diagnosis of EHMs were 100% and 88%, respectively. Conclusions: We constructed and validated a nomogram on predicting the risk of EHMs in patients with CRLMs, which can guide clinicians to selective application of ¹⁸F-FDG PET/CT.

Purpose: The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Methods: Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. Additionally, Cochran's Q and MR-Egger tests were utilized to evaluate the heterogeneity and horizontal pleiotropy, respectively. Simultaneously, the reliability of MR results was evaluated by leave-one-out (LOO) method. Finally, multivariable MR (MVMR) analysis and mediation analysis were performed to further reveal the mechanism of mediation effect among the three diseases. Results: With regard to the results of IVW method, both iridocyclitis (P=0.0185, OR=1.0757) and psoriasis (P=0.0115, OR=1.1246) had significant causal relationships with the occurrence of NAFLD, and both were risk factors for NAFLD. Besides, it was observed that there was significant causal effect of iridocyclitis (P= 0.0181, OR=1.1729) on psoriasis and iridocyclitis was a risk factor. Additionally, there was a lack of heterogeneity (P>0.05) among the selected SNPs when MR analysis was conducted with NAFLD as the outcome. Horizontal pleiotropy was not detected by the MR-Egger test. The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. Conclusion: This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD.

Background: The lengthy period of external fixation for bone consolidation increases the risk of complications during distraction osteogenesis (DO). Both pro-angiogenic and osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) contribute to bone regeneration during DO. The underlying mechanism of Schwann cells (SCs) in promoting bone regeneration during DO remains poorly understood. Methods: The impacts of RSC-96 on the proliferation, migration, and osteogenic differentiation of BMSCs in the coculture system were investigated. The pro-angiogenic potential of BMSCs was evaluated by migration and tube formation assay. Quantitative real-time PCR was used to analyze angiogenic and osteogenic markers. ELISA was used to detect the secretion of various neurotrophins. Protein expressions of Activate protein kinase B (AKT)/β-catenin signaling were assessed by western blot. In vivo, dynamic expression levels of neurotrophic factors were detected in a preclinical rat DO model. Promotive effects of vascularization and mineralization provided by RSC-96 derived conditioned medium (CM) in a rat DO model were verified radiologically, biomechanically and histologically. Result: Coculture system with RSC-96 promoted osteogenic ability of BMSCs, with increased cell viability, alkaline phosphatase staining, mineralized nodule formation, and osteogenic gene expression. Additionally, increased angiogenic gene expression of BMSCs and angiogenic capacity of endothelial cells demonstrated enhanced pro-angiogenic potential of BMSCs. Secretion of angiogenic and neurotrophic factors were enhanced in the coculture system. These effects were accompanied by activation of AKT/GSK-3β/β-catenin signaling, as evidenced by western blot analysis and the inhibitory effect of AKT inhibitor. The mRNA expression of neurotrophic factors peaked at the end of the distraction phase during DO. Furthermore, RSC-96 derived CM accelerated bone regeneration, resulting in improved biomechanical parameters, radiological features and histological manifestations, along with increased vascularization in the distraction area. Conclusion: Through activation of AKT/GSK-3β/β-catenin signaling, SCs enhanced the coupled angio- and osteogenesis effects of BMSCs. The preclinical evidence demonstrates that SCs derived CM with increased neurotrophins secretion can be a promising treatment approach to accelerate bone regeneration in the DO process.

Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3^-/-) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis. Our study observed significant Ripk3 upregulation in lipopolysaccharide- (LPS-) treated lung tissues, as well as in murine pulmonary microvascular endothelial cells (PMVECs). Ripk3 deletion improved lung tissue morphology, reduced inflammation, oxidative stress and endothelial dysfunction under LPS challenge. It also mitigated LPS-induced necroptosis and mitochondrial damage in PMVECs. Ripk3 upregulation suppressed the AMP-activated protein kinase (AMPK) pathway and activated Drp1-mediated mitochondrial fission, increasing mitochondrial permeability transition pore (mPTP) opening and PMVEC necroptosis. Conversely, Ripk3 deletion activated the AMPK/Drp1-mitochondrial fission pathway, preventing mPTP opening and PMVEC necroptosis in ALI. These findings demonstrated that Ripk3 promotes necroptosis through the AMPK/Drp1/mPTP opening pathway, identifying a potential therapeutic target for ALI treatment.

Background: The relationship between maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) status and hypertensive disorders of pregnancy (HDP) remains uncertain. Methods: This was a prospective cohort study based on the China Birth Cohort Study (CBCS). 36,256 women were included at 6 to 13⁺⁶ gestation from February 2018 to December 2020. Generalized linear mixed models were used to investigate the association between thyroid function and HDP/BP. We further performed multiple subgroup analyses to test the robustness of this association. Results: The final study population was 25,608, and the overall incidence of HDP was 8.0%. After adjusting for maternal age, pre-pregnancy BMI, education, household annual income, smoking status, conception method and parity, the odds of HDP increased by 3.0% with a 1-unit increase in TSH (OR 1.03, 95% CI 1.04-1.06). Maternal TSH and TPOAb positivity were associated with a higher risk of preeclampsia or eclampsia but not gestational hypertension (TSH: OR 1.04, 95% CI 1.01-1.07; TPOAb positivity: OR 1.30, 95% CI 1.09-1.56). TSH and TPOAb positivity were significantly and positively associated with systolic pressure (TSH: β 0.02, 95% CI 0.07-0.26; TPOAb positivity: β 0.02, 95% CI 0.12-0.98) and diastolic pressure (TSH: β 0.02, 95% CI 0.02-0.17; TPOAb positivity: β 0.02, 95% CI 0.06-0.75). Subgroup analyses suggested that the association between TSH and diastolic pressure was stronger in those with BMI ≥ 25 kg/m² (P = 0.014). Conclusions: Our founds suggest that high TSH and TPOAb positivity in the first trimester are associated with an increased risk of preeclampsia or eclampsia.

Autoimmune inner ear disease (AIED) is a rare condition characterized by immune-mediated damage to the inner ear, leading to progressive sensorineural hearing loss (SNHL) and vestibular symptoms such as vertigo and tinnitus. This study investigates the pathogenesis and therapeutic strategies for AIED through the analysis of three cases with different underlying autoimmune disorders: rheumatoid arthritis, relapsing polychondritis, and IgG4-related disease. The etiology of AIED involves complex immunopathological mechanisms, including molecular mimicry and the "bystander effect," with specific autoantibodies, such as those against heat shock protein 70 (HSP70), playing a potential role in cochlear damage. Diagnosis remains challenging due to nonspecific symptoms and the lack of distinct biomarkers, emphasizing the need for comprehensive clinical evaluation and exclusion of other hearing loss causes. Treatment primarily involves immunosuppressive therapies, with glucocorticoids as the first line, effective in 70% of cases. However, resistance or partial response necessitates the use of additional agents like methotrexate and biologics such as anti-TNF and IL-6 receptor antagonists. Early intervention is crucial for favorable outcomes, as demonstrated in the studied cases, where timely corticosteroid and immunosuppressive treatments led to significant hearing improvement. The study underscores the importance of personalized treatment strategies based on individual immunologic profiles and comorbidities. Our findings highlight the heterogeneity of AIED and the potential for biologic therapies in refractory cases.

Introduction: LN18178 is a standardized, synergistic combination of Punica granatum fruit rind and Theobroma cacao seed extracts, which has been reported to increase serum testosterone levels in young and aging males. Methods: The present 84-day randomized, double-blind, placebo-controlled study assessed the efficacy of LN18178 on the sexual function of aging male volunteers (age: 40-70 years; serum total testosterone: ≥ 300 ng/dL). The subjects with mild to moderate erectile dysfunction [5-item version of the International Index of Erectile Function (IIEF-5) scores 17-25] and low sexual desire (score < 3 on items 11 and 12 of IIEF) participated in this investigation. One hundred and twenty men were randomly allocated into either the LN18178 or placebo group (n=60); they took either 400 mg of LN18178 or a matched placebo capsule daily with breakfast. Results: Post-trial, the LN18178-supplemented participants reported significant (P < 0.05) improvements in total and domain scores of the Derogatis Interview for Sexual Functioning-Self Reporting Male (DISF-SR-M) questionnaire, as well as substantial improvements in IIEF-5 (International Index of Erectile Function-5) and erection hardness scores (EHS). Comparative analysis also revealed significant improvements in the multi-dimensional fatigue inventory (MFI) and general health survey (GHS) scores. LN18178 supplementation substantially (P < 0.05) increased the six-minute walk distance and hand-grip strength compared to placebo. The participants' hemato-biochemical parameters, urinalysis, and vitals were within the normal range. Conclusion: LN18178 enhances sexual function, libido and improves psychological well-being, as well as neuromotor function and general well-being in aging males. LN18178 supplementation is safe and well tolerated by the participants.

Diabetic retinopathy (DR) is a microvascular complication of diabetes characterized by an inflammatory response. The H19 gene plays a role in regulating inflammation and is associated with chronic systemic inflammation. This study aims to investigate the potential correlation between single-nucleotide polymorphisms (SNPs) in the H19 gene and the development of DR. Five loci of H19 SNPs-rs3024270 (C/G), rs2839698 (C/T), rs3741219 (A/G), rs2107425 (C/T), and rs217727 (C/T)-were genotyped using TaqMan allelic discrimination in 454 individuals without DR and 272 DR participants. The results indicate that the H19 SNP rs3741219 AG (p = 0.030) and AG+GG (p = 0.037) alleles are significantly associated with an increased risk of developing DR in individuals with diabetes onset before the age of 45. Additionally, diabetic individuals with the H19 SNP rs3741219 AG+GG genotype also showed significantly higher serum creatinine (p = 0.034), lower glomerular filtration rate (GFR) (p = 0.013), higher total cholesterol/HDL ratio (p = 0.031), and higher triglycerides (p = 0.012). In an age-based subgroup analysis, GFR was significantly lower in diabetic patients with an onset of diabetes before 45 years and with the H19 SNP rs3741219 AG+GG genotype (p = 0.012). In conclusion, the presence of the H19 SNP rs3741219 variant is associated with a higher risk of DR in individuals with early-onset diabetes, and the relationship between the rs3741219 variant and decreased GFR is particularly pronounced in this population.

Purpose: Pancreatic cancer has the worst prognosis of all common cancers worldwide. Cadherin plays important roles in cancer cell invasion and metastasis. This study investigated the role and mechanism of Cadherin 23 (CDH23) action in the viability of pancreatic cancer cells. Methods: We examined CDH23 expression in 70 surgical pancreatic cancer samples and examined relationships among the level of CDH23 expression, clinicopathological characteristics, and the prognosis of the pancreatic cancer patients. Furthermore, we silenced CDH23 expression in pancreatic cancer cell lines (Panc-1, SUIT-2, MIA PaCa-2, CFPAC-1, and Capan-2) and assessed the viability of these cells. CDH23 expression in pancreatic cancer patients and cell lines was examined using immunohistochemistry and western blotting. Results: High levels of CDH23 in pancreatic cancer patients led to shorter overall survival and correlated with local recurrence and distance metastasis. The viability of pancreatic cancer cells in floating culture conditions decreased sharply when CDH23 was silenced. The viability and migration of pancreatic cancer cells in monolayer culture conditions did not change when CDH23 was silenced. The level of phosphorylated AKT was significantly decreased in the CDH23 knockdown cells in floating culture conditions. Conclusion: High levels of CDH23 expression are correlated with a poor prognosis in pancreatic cancer and may serve as a novel prognostic marker.

Effective therapies for cognitive impairments induced by brain irradiation are currently lacking. This study investigated the therapeutic potential of hyperbaric oxygen therapy (HBOT) for radiation-induced brain injury in a randomized controlled experimental model using adult male Wistar rats. Adult male Wistar rats were divided into four experimental groups: 0 Gy whole brain radiotherapy (WBRT) with normal baric air (NBA) treatment, 0 Gy WBRT with HBOT, 10 Gy WBRT with NBA, and 10 Gy WBRT with HBOT. Behavioral tests and histochemical analyses were conducted four weeks post-WBRT to assess cognitive function, hippocampal microgliosis, apoptosis, and lipid peroxidation. Compared with the rats with 0 Gy WBRT on 28 days, the rats with 10 Gy WBRT on 28 days had significantly higher severity of spatial learning and memory dysfunction and hippocampal microgliosis, newborn neuronal apoptosis, and lipid peroxidation. HBOT significantly prevented and reversed WBRT-induced cognitive deficits, hippocampal microgliosis, newborn neuronal apoptosis, and lipid peroxidation. In addition, HBOT prevented and reversed the increased apoptosis among newborn neural stem cells and neuroblasts caused by 10 Gy WBRT on 7 days. The findings suggest that WBRT disrupts neurogenesis and enhance microgliosis, apoptosis of neuronal progenitors, and lipid peroxidation in the dentate gyrus, potentially leading to cognitive deficits and neuronal death. HBOT may offer a protective effect against these cognitive impairments and their underlying mechanisms in adult male rats following WBRT.