Journal of clinical medicine research最新文献

Background: Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder with significant global morbidity and mortality. COPD is increasingly recognized as a systemic inflammatory condition that predisposes patients to multiple comorbidities, including tuberculosis (TB). There are limited data on how comorbidities in COPD influence the development of TB.

Methods: We conducted a nationwide, retrospective cohort study using data from Taiwan's National Health Insurance Research Database (NHIRD) between 2011 and 2021. Patients aged ≥ 40 years with a diagnosis of COPD, confirmed by ≥ 3 outpatient visits or ≥ 1 hospitalization, were included. Individuals with prior TB were excluded. Non-COPD controls were matched 1:1 using propensity score matching for demographics and comorbidities. The primary outcome was incident TB (ICD-9-CM 010-018). Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for TB, accounting for a variety of comorbidities.

Results: A total of 117,989 COPD patients and an equal number of matched controls were analyzed. During follow-up, TB incidence was significantly higher in the COPD group (3.20 vs. 1.45 per 10,000 person-years). COPD was associated with a 74% increased risk of TB (aHR 1.74; 95% confidence interval (CI): 1.42 - 2.14; P < 0.001). Stratified analysis demonstrated that TB risk rose progressively with age and was markedly amplified by comorbidities. Notably, pneumoconiosis conferred a nearly sevenfold higher TB risk among COPD patients (aHR 6.94; 95% CI: 2.72 - 17.71; P < 0.001), followed by lung cancer (aHR 1.81; 95% CI: 1.07 - 3.05; P < 0.027) and rheumatoid arthritis (aHR 2.05; 95% CI: 1.01 - 4.12; P < 0.046).

Conclusion: After adjustment for available covariates, COPD was associated with an increased risk of TB; however, residual confounding due to factors such as corticosteroid use, immunosuppressive therapy, and smoking cannot be excluded.

The aim of this study was to review the neurobiological mechanisms, epidemiology, and therapeutic interventions for non-suicidal self-injury (NSSI), emphasizing the pain addiction model and electroencephalographic biomarkers as frameworks for precision intervention. A narrative review of the literature was conducted using PubMed, Web of Science, CNKI, and Wanfang Data up to October 2025. Search strategy employed the terms "non-suicidal self-injury," "pain addiction," "electroencephalography," "endogenous opioid system," and "HPA axis." Selection criteria prioritized original human studies, high-quality systematic reviews, and mechanistic investigations. Pain addiction and electroencephalography (EEG) were selected as focal variables based on their explanatory power: pain addiction elucidates NSSI perpetuation through endogenous opioid-mediated reward sensitization and dopaminergic reinforcement, while event-related potentials (ERPs) provide temporal precision in mapping cognitive-affective dysregulation underlying emotional impulsivity and regulatory deficits. Global adolescent NSSI prevalence averages 17.2%, with Chinese rates reaching 24.7% and trends toward earlier onset. Neurobiological substrates include fronto-limbic dysregulation, hypoactive hypothalamic-pituitary-adrenal (HPA) axis function with blunted cortisol reactivity, and endogenous opioid system alterations producing widespread hypoalgesia. EEG/ERP studies demonstrate increased N2 amplitude with decreased P3 amplitude and prolonged latency during negative stimuli processing, reflecting impaired conflict monitoring and attentional resource allocation. Dialectical behavior therapy shows established efficacy, while repetitive transcranial magnetic stimulation and opioid antagonists demonstrate therapeutic potential. NSSI emerges from neurobiological vulnerability within pain-reward-emotion circuits interacting with psychosocial factors. The pain addiction framework and EEG signatures provide translatable targets for biomarker development and personalized intervention. Future research requires multimodal neuroimaging, longitudinal designs, and genetic integration to establish predictive algorithms and precision therapeutics.

The immune system plays a vital role in defending the body against infections and tumors, inspiring the development of innovative therapies like immune checkpoint inhibitors (ICIs) that have transformed the treatment of advanced cancers. Pembrolizumab, a monoclonal antibody targeting the programmed cell death 1 (PD-1) receptor, is a powerful ICI effective against various malignancies but frequently associated with immune-related adverse events (irAEs). In this report, we present a case of organizing pneumonitis that developed 3 months after initiation of pembrolizumab treatment for non-small cell lung cancer (NSCLC). A 64-year-old woman with NSCLC, undergoing maintenance therapy with pembrolizumab, presented with multiple lung consolidations. Her medical history included thalassemia minor, a pre-pyloric ulcer, hiatal hernia, and a history of smoking. Extensive microbiological testing, including bronchoalveolar lavage, was negative, and her condition did not improve with broad-spectrum antibiotics. This led to a suspected diagnosis of pembrolizumab-induced pneumonitis. Treatment with high-dose corticosteroids resulted in full clinical and radiological resolution. This case underscores the importance of monitoring for irAEs during ICI therapy, as differential diagnosis between immunotherapy-induced organizing pneumonia and tumor progression is challenging in patients with advanced lung cancer.

Background: This preliminary study investigated the effect of aged garlic extract (AGE) on acetic acid (AA) and/or 5-fluorouracil (5-FU)-induced oral mucositis in tumor-bearing mice, and whether AGE affects the antitumor activity of 5-FU.

Methods: There were four mouse groups: control, AA, AA + 5-FU, and AA + 5-FU + AGE. Mouse squamous cell carcinoma cells (SCCVII) were used to develop tumors in mice, except for the control group. Oral mucositis was induced in tumor-bearing mice by intraperitoneal injection with 5-FU (18 mg/kg) for 9 days and/or topical application of 50% AA to the dorsal tongue for 1 day. Mucositis was treated with AGE (2.0 g/kg/day) for 10 days in AA + 5-FU + AGE group, while the other groups received saline (0.2 mL/day). The wound healing and antitumor effects of AGE were examined. Whole transcriptome analysis and ingenuity pathways analysis (IPA) of the tongue and tumor samples were used to investigate the mechanisms behind the wound healing and antitumor effects of AGE.

Results: Body weight was increased significantly in AA + 5-FU + AGE group compared to AA + 5-FU group. Moreover, tumor volume was significantly decreased in AA + 5-FU + AGE group than that in the other groups. In AA + 5-FU group, toluidine blue-positive area (wound area) in the tongue was the largest, and the size and weight of the salivary glands were decreased compared to other groups. In contrast, wound area was significantly reduced, and the size and weight of the salivary glands were increased in AA + 5-FU + AGE group compared to AA + 5-FU group. Therefore, AGE treatment could heal tongue ulcers and salivary gland damage in AA + 5-FU + AGE group. Whole transcriptome analysis and IPA data suggested that AGE could heal 5-FU-induced oral mucositis by promoting normal cell differentiation and keratinization, and it may also enhance the antitumor effects of 5-FU through the activation of B cells in mouse tumors.

Conclusion: AGE could alleviate AA and 5-FU-induced oral mucositis in mice while potentially enhancing the antitumor activity of 5-FU. Therefore, AGE might be useful in the treatment of oral mucositis in cancer patients receiving 5-FU-based therapies.

Background: Cardiovascular disease (CVD) remains a leading global cause of mortality. Statins, particularly rosuvastatin (RSV), are widely used to reduce low-density lipoprotein cholesterol (LDL-C) level and prevent atherosclerotic CVD. RSV is highly liver-selective, hydrophilic, and primarily transported via organic anion transport proteins, rendering it less prone to cytochrome P450-mediated drug interactions. However, the concurrent use with magnesium oxide (MgO), a common antacid and laxative, has been shown to decrease RSV absorption by up to 50%, raising concerns regarding the clinical efficacy of RSV in patients taking MgO.

Methods: This multicenter, randomized, parallel-group comparative trial included outpatients prescribed both RSV and MgO at Fukuoka University Chikushi and Fukuoka Tokushukai Hospitals. Patients were randomly assigned to the control group with simultaneous administration or the intervention group with staggered administration of MgO at least 2 h after RSV. Data on demographics and serum levels of LDL-C, total cholesterol, high-density lipoprotein cholesterol, and triglycerides were collected at baseline and 12 weeks after study initiation. Medication adherence was monitored using a self-reported medication checklist, and patients with ≥ 80% compliance were included in the final analysis.

Results: A total of 45 patients, including 25 and 20 patients in the control and intervention groups, respectively, completed the study. The median ages were 78 and 76 years in the control and intervention groups, respectively. The baseline demographics and clinical parameters, including LDL-C, were not significantly different between the two groups. After 12 weeks, the rate of change in LDL-C level was not significantly between the control and intervention groups (P = 0.9091).

Conclusion: The concurrent use of RSV and MgO did not significantly impact the reduction in LDL-C levels compared with the staggered administration. Simplifying administration without altering efficacy can improve medication adherence, particularly in elderly patients and those with polypharmacy, by reducing treatment complexity.

Background: Although guidelines recommend gradual blood pressure (BP) reduction in asymptomatic markedly elevated BP (AMEBP), short-acting oral antihypertensives are often used despite limited evidence - driven by healthcare providers' concerns or institutional policies - thereby increasing system burden. This study aimed to identify practical regimens enabling safe, timely discharge and continuity of care.

Methods: This retrospective cohort included patients with AMEBP (systolic BP > 180 mm Hg and/or diastolic BP > 110 mm Hg), who presented to the emergency department (ED) of Lampang Hospital between January and December 2023. Oral regimens included captopril, hydralazine, metoprolol (25 mg each), or combinations. The outcome was mean arterial pressure (MAP) reduction within 60 min, classified as no reduction (< 10%), appropriate reduction (10-15%), or over-reduction (> 15%). Inverse probability of treatment weighting (IPTW) adjusted for regimen selection, and multinomial odds ratios (mORs) with 95% confidence intervals (CIs) were reported.

Results: Among 158 patients (mean age 60 years; 67.1% female), baseline MAP was 142.4 ± 16.2 mm Hg. Captopril and hydralazine monotherapy were most likely to achieve appropriate reduction (captopril: mOR: 2.91; 95% CI: 0.96, 8.76; P = 0.058; hydralazine: mOR: 2.76; 95% CI: 0.84, 9.11; P = 0.096). Metoprolol was associated with inappropriate response, while captopril plus hydralazine had highest odds of over-reduction (mOR: 3.04; 95% CI: 1.02, 9.00; P = 0.045).

Conclusions: Although urgent BP reduction is not routinely recommended in the ED, oral captopril appears to be a reasonable first-line option when clinically necessary, while hydralazine may be a suitable alternative. Combination of these two drugs should be used with caution due to the risk of excessive MAP reduction.

Background: Intracranial hemorrhage (ICH) is a major complication of intravenous alteplase for acute ischemic stroke. Asymptomatic ICH (asICH) does not cause immediate neurological decline but may have medicolegal consequences if undetected. In Asian populations, up to 24% of post-alteplase ICH occurs beyond 24 h, suggesting that routine computed tomography (CT) at 24 h may underestimate its incidence. This study evaluated the diagnostic yield of CT at 24 h versus 48 h to determine the optimal timing for ICH detection.

Methods: A retrospective cohort study was conducted at Lampang Hospital from March 2017 to December 2024. Patient outcomes were analyzed using an illness-death multistate model with three health states: no ICH, asICH, and symptomatic ICH (sICH). Three transitions were modeled - from no ICH to asICH, from no ICH to sICH, and from asICH to sICH - assuming irreversible progression. The proportions of asICH detected by CT at 24 h versus 48 h were compared using the exact probability test.

Results: After exclusions, a total of 555 patients were eligible (54.8% male, mean age 65 years). Final transition outcomes identified 455 patients with no ICH, 51 with asICH, and 49 with sICH. Brain CT at 24 h detected 30.2% of asICH cases, while 48-h imaging detected 96.8%, with a significant improvement (P < 0.001).

Conclusions: CT imaging at 48 h post-alteplase improves asICH detection compared with the 24-h scan, reducing missed cases without added radiation or resource burden. Multicenter validation is needed to confirm whether 48 h should replace the current standard.

Background: Coronavirus disease 2019 (COVID-19) and obesity remain pressing global health concerns. Identifying predictors of severe disease is of particular importance. Pericardial fat tissue (PFT) is a known source of metainflammation due to its secretion of adipocytokines and inflammatory mediators. Moreover, cytokine storm plays a major role in COVID-19-related mortality. This study aimed to investigate the association between preexisting PFT volume and inflammatory markers in patients with COVID-19.

Methods: The study included 290 hospitalized patients with confirmed COVID-19 infection. Based on PFT volume (above or below 3.45 cm³), patients were divided into two groups: with and without pericardial obesity (PO), consisting of 132 and 158 individuals, respectively. Clinical, laboratory, and imaging data were analyzed. Statistical analysis was performed in Statistica 12.0.

Results: Significant intergroup differences were observed in the PO group for the following variables: male sex (P < 0.001), body mass index (BMI) (P < 0.001), obesity (P < 0.001), and history of diabetes mellitus (P = 0.003). No significant differences were found in lung computed tomography (CT) severity scores. However, patients with PO showed significantly lower oxygen saturation (SpO₂) levels (P = 0.014) and a higher frequency of SpO₂ ≤ 93% (P = 0.012). Ferritin levels were significantly higher in the PO group (median 440 (274.00 - 552.70) vs. 292.55 (156.00 - 521.50), P = 0.010). Linear correlation analysis revealed a positive association between PFT volume and age, BMI, glucose, ferritin, C-reactive protein, and D-dimer levels, and a negative correlation with oxygen saturation. Multivariate logistic regression confirmed an independent association between PFT volume and SpO₂ ≤ 93%. Receiver operating characteristic (ROC) analysis identified a threshold PFT volume of 3.45 cm³ for predicting increased risk of severe COVID-19 (SpO₂ ≤ 93%), with sensitivity of 66.7%, specificity of 65.0%, and area under the curve (AUC) of 0.710 (95% confidence interval (CI): 0.551 - 0.868, P < 0.001).

Conclusions: Our data suggest that a PFT volume greater than 3.45 cm³ is a potential predictor of severe COVID-19.

Background: In the absence of sepsis, patients with fever and leukocytosis in the emergency department (ED) are often treated with ambulatory parenteral antibiotics at the physician's discretion. Identifying effective regimens for reducing white blood cell (WBC) count and improving clinical outcomes may support standardized ED care.

Methods: This retrospective cohort included adult ED patients with fever and leukocytosis, but without sepsis, in whom basic investigation revealed no clear source of infection. Patients received one of three regimens: (A) single-day intravenous (IV) ceftriaxone followed by oral cefixime, (B) 3-day IV ceftriaxone followed by oral cefixime, or (C) 3-day IV ceftriaxone plus oral doxycycline from day 1. Demographics, baseline data, and laboratory results were collected. Follow-up assessments included WBC count and clinical improvement. Treatment probabilities were estimated with multinomial logistic regression, and stabilized inverse probability of treatment weighting (IPTW) were applied in weighted quantile regression.

Results: Among 250 patients, most were female (63.2%) with a mean age of 49 years. After adjustment, regimen C showed a median WBC reduction of -6.9 × 10³ cells/mm³ (95% confidence interval (CI): -7.5 to -6.3), compared with -6.8 × 10³ (95% CI: -7.2 to -6.5) for regimen B and -6.6 × 10³ (95% CI: -7.0 to -6.2) for regimen A. Differences were not significant (Wald test, P = 0.484), but graphical analysis suggested the steepest decline with regimen C.

Conclusion: Though regimen C showed the steepest WBC decline and fewer failures, the study was markedly underpowered (< 10%). Larger multicenter studies are required to confirm these findings.

Aging is a complicated biological process that induces a decline in the human organs' structure and function and elevates the risks of aging-related diseases such as Alzheimer's disease (AD) and type 2 diabetes. Type 2 diabetes accelerates all clinical manifestations of aging. Metabolic disorders in type 2 diabetes are unfavorably associated with all hallmarks of aging, such as inflammation and mitochondrial dysfunction. Adenosine monophosphate-activated protein kinase (AMPK) and the mammalian target of rapamycin complex 1 (mTORC1) are key players in cellular metabolism, and AMPK activation and mTORC1 inhibition improve all hallmarks of aging. AMPK activation and mTORC1 inhibition are favorably associated with diabetic complications. Nutritional interventions, such as caloric restriction, resveratrol, and astaxanthin, have AMPK-activating and mTORC1-inhibitory effects and improve metabolic abnormalities in type 2 diabetes. Anti-diabetic drugs, metformin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide 1 receptor agonists have been reported to have AMPK-activating and mTORC1-inhibiting effects and show prevention of aging-related diseases such as cardiovascular disease. The therapeutic interventions that activate AMPK and inhibit mTORC1 may be optimal treatments for type 2 diabetes from the perspective of anti-aging medicine. Furthermore, senolytics may be a promising, direct anti-aging therapeutic strategy specifically for type 2 diabetes and its complications.