International Journal of Medical Sciences最新文献

Background: Chronic periodontal disease (CPD) may contribute to systemic inflammation and adverse outcomes in patients undergoing maintenance hemodialysis, but age-specific risks remain unclear. We aimed to evaluate the association between CPD and clinical outcomes in hemodialysis patients, stratified by age. Methods: We conducted a retrospective cohort study using the TriNetX Research Network. Adults aged 45-64 or ≥65 years initiating maintenance hemodialysis were included. CPD exposure was defined using ICD-10-CM codes documented within 6 months before or up to 5 years after hemodialysis initiation. Outcomes included all-cause mortality, pneumonia, fracture, and major adverse cardiovascular events (MACE) over a 5-year follow-up period. Propensity score matching was conducted within each age group using a comprehensive model that included age, sex, race, comorbidities, medications, and laboratory values. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox models. Subgroup and sensitivity analyses were conducted to assess robustness and effect modification. Results: CPD was significantly associated with increased risks of all-cause mortality in both younger (aHR = 1.313, 95% CI: 1.129-1.527; p<0.001) and older patients (aHR = 1.126, 95% CI: 1.048-1.209; p=0.001), with stronger associations in the younger group. Subgroup analysis showed elevated mortality risks in younger males, females, and non-diabetic individuals. Pneumonia risk was significantly increased across both age groups, with particularly high risks in younger females and older males. CPD was also associated with a higher risk of fracture, particularly among older adults (aHR = 1.673, 95% CI: 1.375-2.036; p<0.001), with consistent findings across subgroups. No significant associations were observed between CPD and MACE in either age stratum. Sensitivity analyses adjusting for comorbidities and inflammatory markers supported the primary findings. Conclusion: CPD is associated with increased risks of mortality, pneumonia, and fractures among hemodialysis patients, with variation by age and clinical subgroup. These findings support integrating periodontal screening and preventive strategies into hemodialysis care. Younger patients may benefit from early intervention to reduce infection and mortality risk, while older adults may require targeted skeletal protection.

Background: Tuberculosis is a communicable disease that is a major cause of ill health and one of the leading causes of death worldwide. Latent tuberculosis infection (LTBI) widely exists in people all over the world, especially in patients with unexplained infertility, and the relationship between latent tuberculosis infection and ovarian reserve, as well as pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), remains poorly understood. Methods: A single-center, retrospective cohort study was conducted at the Reproductive Medicine and Genetics Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between January 2018 and December 2020. The study aimed to investigate whether LTBI affects ovarian reserve and pregnancy outcomes in infertile women undergoing assisted reproductive technology. The primary outcomes were ovarian reserve and cumulative live birth rate per IVF/ICSI cycle, while secondary outcomes included pregnancy outcomes and maternal and neonatal complications. Results: A total of 11523 assisted reproductive technology cycles were ultimately included in the comparison of ovarian reserves, and 9141 IVF/ICSI cycles were ultimately included in the comparison of clinical outcomes between the LTBI and control groups. The data revealed that women with LTBI had significantly lower anti-Müllerian hormone (4.61 ± 3.99 ng/mL vs. 4.88 ± 4.22 ng/mL, P=0.035, β=-0.23, 95% CI -0.43 to -0.04) and antral follicle counts [11.00 (8.00, 17.00) vs. 12.00 (8.00, 19.00), P=0.048, β=-0.26, 95% CI -0.53 to -0.01]. The conservative and optimistic cumulative live birth rates (61.42% vs. 61.94%, adjusted OR: 0.95, 95% CI: 0.82-1.10; 72.65% vs. 73.25%, adjusted OR: 0.94, 95% CI: 0.78-1.14), the live birth rates after fresh embryo transfer (39.28% vs. 40.83%, adjusted OR: 0.97, 95% CI: 0.82-1.14) and other secondary outcomes in the LTBI group were comparable to those in the control group after excluding factors such as age, ovarian reserve, and the number of oocytes retrieved. Conclusions: LTBI may affect the ovarian reserve but not directly affect the pregnancy outcomes of IVF/ICSI in infertile women.

Background: C-type lectin-like receptor 2 (CLEC-2) is involved in platelet activation, tumor metastasis, and vessel differentiation, but its role in breast cancer remains unclear. This study examined the association between clinical status and plasma levels of CLEC-2 in patients with breast cancer. Methods: Plasma CLEC-2 concentrations were measured using ELISA in breast cancer patients and control subjects. A total of 98 breast cancer patients and 98 age-matched control subjects were enrolled. All study participants were female. Results: CLEC-2 concentrations were significantly lower in the breast cancer patients (231.2 [213.5-250.9] ng/mL) than in the controls (249.2 [235.8-263.4] ng/mL, p < 0.0001). Plasma CLEC-2 levels were lower in patients with advanced stages (T3+T4, AJCC III-IV), histologic grade > 3, and tumor size ≥5 cm. Kaplan-Meier analysis revealed a higher overall survival rate in the patients with a high CLEC-2 levels than in those with a low CLEC-2 levels (p = 0.035). Univariate Cox analysis showed that a high CLEC-2 level was independently associated with better overall survival. Spearman correlation analysis showed that CLEC-2 plasma levels were positively correlated with stages T0-T2, grades 1-2, ALT, APRI, and tumor size <2 cm, but negatively correlated with platelet count. Conclusion: Our findings suggest that lower plasma CLEC-2 levels are associated with advanced breast cancer features. CLEC-2 is significantly associated with breast cancer prognosis and may serve as a prognostic marker in patients with breast cancer.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second leading cause of cancer-related mortality. Prognostic prediction in HCC is complicated by its heterogeneity, and current treatment strategies are limited to surgical resection and targeted therapies. Sorafenib, a multi-kinase inhibitor and the first-line systemic therapy for advanced HCC, offers modest survival benefits and often induces resistance during long-term administration. Therefore, elucidating the molecular mechanisms of drug resistance is critical for improving therapeutic outcomes. Triptolide is a diterpenoid triepoxide extracted from the traditional Chinese herb Tripterygium wilfordii, exhibits potent anti-inflammatory and anti-neoplastic properties in various cancer types. CARMA3 (CARD10), a membrane-associated scaffold protein, has recently emerged as a key oncogenic regulator in solid tumors. This study demonstrates that CARMA3 contributes to chemoresistance in HCC and that triptolide enhances chemosensitivity by downregulating CARMA3 expression and promoting reactive oxygen species (ROS) accumulation. Our findings suggest that triptolide functions as a chemosensitizing agent by modulating CARMA3-mediated ROS accumulation and ferroptosis resistance, offering a novel therapeutic strategy for overcoming HCC drug resistance.

The global rise in obesity has contributed to the increasing prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD, formerly known as non-alcoholic fatty liver disease, NAFLD), which is strongly linked to insulin resistance and progression to advanced liver diseases. Dietary factors are thought to influence its development and progression. We aimed to investigate the effect of green tea containing inulin and catechin (IC-GT) on high-fat diet (HFD)-induced MAFLD. Male C57BL/6 mice were assigned to five groups (10 mice/group): control (0 mg IC-GT/kg BW/d), HFD (0 mg IC-GT/kg BW/d), IC-GT-0.5X (1,328 mg IC-GT/kg BW/d), IC-GT-1X (2,645 mg IC-GT/kg BW/d), and IC-GT-2X (5,289 mg IC-GT/kg BW/d). All mice in each group were gavage-fed, received water or test samples for one week, and were then fed an HFD for 18 weeks. Blood and liver tissues were analyzed for lipid profile, enzyme activities, and histopathology. We found that IC-GT supplementation for 18 consecutive weeks significantly reduced aspartate transaminase and alanine transaminase activity as well as total cholesterol, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations in the blood after HFD intake, and decreased the accumulation of TC and TG in the liver. In addition, histopathological analyses showed a significant reduction in hepatic lipid droplet accumulation. Therefore, our findings suggest that long-term supplementation of IC-GT can significantly ameliorate HFD-induced MAFLD.

Proliferative vitreoretinopathy (PVR) is a retinal disorder characterized by abnormal growth and migration of retinal pigment epithelium (RPE) cells, leading to impaired visual acuity. Tricin is a naturally occurring flavone known to inhibit the migration of various cancer cell types. Therefore, the aim of this study was to investigate the potential inhibitory effects of tricin on the migration of ARPE-19 cells. In this study, tricin treatment significantly reduced the migratory and invasive abilities of ARPE-19 cells in the Boyden chamber assays. RNA sequencing identified cytochrome P450 1A1 (CYP1A1) as the most significantly downregulated gene following tricin treatment. Real-time PCR confirmed a reduction in CYP1A1 mRNA levels, while Western blot analysis demonstrated a concentration-dependent decrease in CYP1A1 protein expression. Moreover, siRNA-mediated knockdown of CYP1A1 resulted in decreased mRNA expression levels, accompanied by reduced cell migration. Tricin treatment also attenuated RUNX2 transcription factor levels and phosphorylation of STAT3. Co-treatment with tricin and colivelin (a STAT3 activator) led to increased CYP1A1 expression and enhanced cell migration, suggesting a regulatory role of the STAT3 pathway in tricin-mediated effects. In conclusion, tricin inhibits the migration of ARPE-19 cells by downregulating CYP1A1 and RUNX2 expression through suppression of the STAT3 signaling pathway. These findings suggest that tricin holds potential as a therapeutic candidate for preventing or limiting the progression of PVR.

Glioblastoma (GB) is a highly aggressive brain cancer with poor prognosis and a five-year survival rate of only 4-5%, largely due to challenges in surgical removal and radiotherapy limitations. Corosolic acid (CA), a natural pentacyclic triterpene, exhibits promising anti-cancer activity against GB. In this study, we founded that GBM8401-derived cancer stem cells (GBM8401-CSCs) display increased stemness, proliferation, migration, invasion, and elevated cancer stemness factors (Nestin, OCT4, CD133) compared to parental cells. CA treatment dose-dependently inhibited these malignant features and downregulated key cancer stemness genes. Combined with Temozolomide (TMZ), CA synergistically suppressed GBM8401-CSCs growth, colony formation, migration, invasion, and promoted apoptosis more effectively than either CA or TMZ alone and significantly reduced sphere formation and cancer stemness gene expression. Molecular docking results show a strong affinity of TMZ and CA for CD133 and OCT4 proteins, highlighting distinct molecular interactions. These results suggest that CA, especially in combination with TMZ, holds therapeutic potential for targeting human GB-CSCs.

Osteoarthritis (OA) is a prevalent condition characterized by inflammatory responses, and joint replacement surgery has been widely utilized for its management over the past several decades. Sleep disorders such as sleep disturbance and obstructive sleep apnea (OSA) are also associated with inflammation and pain. Therefore, the objective of this study was to investigate the association between joint replacement surgery and the subsequent risk of sleep disorders in individuals with OA. A retrospective cohort study was conducted using data from the TriNetX database. Individuals diagnosed with OA were categorized into two groups based on whether they underwent joint replacement surgery. A total of 135,607 individuals were included in both the surgery and non-surgery groups. The primary outcomes of interest were the incidence of sleep disturbance and OSA. A total of 19,146 episodes of sleep disturbance were observed in the surgery group, compared to 25,030 in the non-surgery group. Similarly, 8,715 cases of OSA occurred in the surgery group, whereas 11,472 were reported in the non-surgery group. Both sleep disturbance and OSA exhibited significantly lower incidence rates in the surgery group than in the non-surgery group (P < 0.001 for both). Consistently, cumulative incidence analyses also revealed significantly reduced rates of sleep disturbance and OSA in the surgery group (P < 0.001 for both). In conclusion, joint replacement surgery in patients with OA was associated with a decreased risk of subsequent sleep disorders, including both sleep disturbance and OSA.

Background/Aims: Total parenteral nutrition (TPN) provides medical nutrients intravenously to patients who cannot obtain proper nutrition through normal dietary means or enteral feeding. One significant concern is the risk of liver damage associated with long-term TPN use. In this study, the TPN-associated acute liver injury proteins and the molecular mechanisms underlying TPN oxidative stress were investigated through a quantitative proteomic survey. The proteomic changes between control and TPN infusion rats were analyzed by using the LC-MS/MS iTRAQ technology. Methods: Rats were randomly assigned to saline infusion (control group) and TPN infusion (infusion rate of 30 mL/kg/h for 3 h). At the end of treatment, total liver samples from rats of control and TPN infusion groups were separated by iTRAQ-based quantitative proteomic identification. The effects of the differentially expressed proteins on the potential mechanism of hepatocytes were examined through flow cytometry. Additionally, siRNA-based assessments were conducted to examine the role of the endoplasmic reticulum stress (ER stress) as well as in vivo apoptosis of TPN-related liver cells. Results: The effect of TPN on the biochemical markers of acute liver injury in the experimental rats was examined following palmitic acid treatment of live cells. Forty-eight proteins were differentially expressed between untreated control and TPN infusion liver tissues. The abundances of Elovl5 and Ptbp3 proteins were observed in TPN infusion (P < 0.05). Palmitic acid treatment of liver cells increased cell cytotoxicity and generated ROS, and increased the level of Elovl5 and Ptbp3, validated in the TPN infusion in vivo. The treatment of hepatocytes resulted in the activation of the caspases 3, caspase 9, accompanied by the expression and release of apoptotic molecules, cytochrome c, Bcl-2, Bcl-XL, p-IRE1α, and TRAF2. Elovl5 and Ptbp3 knockdown significantly regulated palmitic acid-mediated cytotoxicity of liver cells, including inhibition of apoptosis and ROS generation. Palmitic acid-mediated apoptotic induction was accompanied by histone H3K4 trimethylation of Elovl5 and Ptbp3 promoters, leading to enhanced transcription through the sustained phosphorylation of ASK1/JNK/p38 pathways. Conclusions: The mechanism of palmitic acid-induced apoptosis cascade and ER stress in hepatocyte cells involves up-regulation of Elovl5 and Ptbp3. This study provides novel regulators underlying the effects of TPN on liver injury.