International Journal of Clinical Practice最新文献

Rationale

Hypertrophic scars are formed as a result of excess collagen and fibroblast activity during the tissue healing process and can result in loss of function. Sinapic acid (SA) is a naturally occurring phenolic compound with antifibrotic, anti-inflammatory, and antioxidant properties.

Aims and Objectives

This study aims to evaluate the ability of SA to inhibit hypertrophic scar generation and explain the mechanisms through which this happens by performing both in vivo and in vitro experiments.

Methods

A rat tail wound model in vivo was employed to assess the impact of SA on the pathological scar area, biomolecule deposition, and fibroblast multiplication. Histopathological, immunohistochemistry, and molecular tests were also performed. Fibroblast cell culture of hypertrophic scar fibroblast cells was used in addition to SA treatment to measure cell growth, movement activity, cell division phases, and fibrotic-related proteins.

Results

In vivo results showed that SA reduced the area of scarring in skin tissues and enhanced the organization of collagen, with the high-concentration group showing the most improvement. The reduction in TGF-β1 and P-SMAD2 was established through immunohistochemistry assays. In vitro findings indicated SA to decrease cell proliferation and movement capabilities of fibroblasts, as well as blocking the G1 phase and resulting in apoptosis. SA also downregulated key fibrosis markers including COL1A1, COL3A1, and α-SMA.

Conclusions

Modulation of the TGF-β1/Smad pathway, reduction of fibroblast proliferation, and the improvement of collagen organization are effects of SA, which aid in attenuation of hypertrophic scar formation. Our findings support the suggestion for further studies in this regard in order to test the safety and efficacy of SA, which can have great potentials for use in antiscarring therapies. These findings provide a mechanistic rationale for the translational development of SA as a topical antiscarring therapy.

Objective

Clinical investigators are essential for assessing the clinical value, safety, and efficacy of innovative drugs. However, comprehensive data on their competency levels are limited in China. This study aimed to evaluate the current status and key determinants of clinical investigators’ competencies.

Methods

We conducted a multicenter, cross-sectional study in 40 tertiary hospitals in Beijing in August 2023, enrolling 1397 clinical investigators. Competency was assessed via a self-administered questionnaire, and influencing factors were identified using multivariate logistic regression.

Results

The median overall competency score was 103 (range: 32–160). Among 194 principal investigators (PIs), prominent competency scores ranged from 25 to 120, with a median of 93. Several factors were significantly associated with higher competency, including advanced education (doctoral degree: aOR = 1.75, 95% CI: 1.21–2.55), professional title (midlevel title: aOR = 1.77, 95% CI: 1.20–2.59; senior-level title: aOR = 2.91, 95% CI: 1.78–4.75), experience leading clinical trials (≥ 1 trial as PI: aOR = 2.38, 95% CI: 1.69–3.36), and GCP training frequency (at least semiannually: aOR = 1.39, 95% CI: 1.07–1.81).

Conclusions

Efforts should target areas of underperformance, particularly by encouraging the pursuit of advanced degrees, senior professional accreditation, PI experience, and regular GCP training. Competency development requires systematic training rather than mere seniority. Consistent GCP training and adherence to international competency standards are crucial for elevating trial quality and facilitating China’s integration into global drug development.

Background

Patients with coronary artery disease (CAD) and Type 2 diabetes mellitus (DM) represent a high-risk population for recurrent cardiovascular events following acute coronary syndrome (ACS). Despite evidence-based guidelines, adherence to secondary prevention strategies remains suboptimal. This study evaluated the impact of comprehensive guideline-based secondary prevention adherence, including contemporary heart failure therapies, on major adverse cardiovascular events (MACE) in patients with CAD and DM post-ACS, extending prior work that examined rehospitalization and all-cause mortality outcomes.

Methods

This retrospective cohort study included 712 patients with confirmed CAD and Type 2 DM who presented with ACS between September 2019 and December 2022. Adherence to ten evidence-based secondary prevention measures was assessed before the index ACS event and at 3-year follow-up, including antiplatelet therapy, high-intensity statins, blood pressure control, ACE inhibitors/ARBs, beta-blockers, SGLT-2 inhibitors, mineralocorticoid receptor antagonists (MRA), angiotensin receptor-neprilysin inhibitors (ARNI), lifestyle modifications, and other guideline-recommended interventions. Patients were stratified into low (≤ 3), moderate (3–6), and high (> 6) adherence groups. Primary outcomes were MACE, including cardiovascular death, nonfatal myocardial infarction, stroke, and urgent revascularization over 3 years.

Results

Mean patient age was 61.7 ± 12.1 years, with 58.4% male participants. Dramatic improvements in adherence occurred post-ACS: high adherence increased from 12.6% to 62.1% (p < 0.001). Significant increases were observed in statin therapy (22.5%–84.7%), antiplatelet therapy (58.3%–91.2%), and blood pressure control (33.6%–87.4%). Cox regression analysis identified better adherence scores as an independent protective factor (HR 0.798, 95% CI 0.686–0.929, p = 0.004). Kaplan–Meier analysis demonstrated superior event-free survival in high adherence patients (88% vs. 70% in the low adherence group, p < 0.001). Statin therapy showed the strongest protective effect (HR 0.512, 95% CI 0.386–0.679, p < 0.001).

Conclusion

ACS events significantly improve adherence to secondary prevention strategies in CAD patients with diabetes, with high adherence associated with substantial reductions in MACE and improved long-term survival.

Introduction

In this study, we aimed to compare the efficacy, safety, and complications of percutaneous nephrolithotomy (PNL) performed in supine and prone positions in elderly patients with staghorn stones.

Materials and Methods

The data of patients over 65 years who underwent PNL due to staghorn stones in the supine or prone position between 2017 and 2024 were retrospectively examined. The patients’ demographic and clinical characteristics and outcomes were compared. Then, univariate and multivariate analyses were performed to determine the factors predicting the development of complications.

Results

The supine (Group 1) (n = 72) and prone (Group 2) (n = 67) PNL groups were similar in terms of mean age, gender, and BMI. The operation time, decrease in hemoglobin levels, and overall complication rates were significantly lower in Group 1 (p < 0.001, p < 0.001, and p = 0.011, respectively). Group 2 demonstrated a significantly higher transfusion requirement (p = 0.039). At the 1-month follow-up, stone-free status was achieved in 52 patients (72.2%) in Group 1 and 42 patients (62.6%) in Group 2. In multivariate analyses, the prone position and lower pole location of the stone were determined as factors predicting the development of complications.

Conclusion

Supine PNL is a safe and effective treatment method with shorter operative time and lower complication rates compared to prone PNL in elderly patients.

Purpose

The aim of the study was to evaluate the causal relationships of oxidative stress–related biomarkers with the risk of cerebral small vessel disease (CSVD) using Mendelian randomization (MR) analysis.

Methods

Summary single-nucleotide polymorphisms (SNPs) linked to oxidative stress–related biomarkers, including uric acid, bilirubin, glutathione transferase (GST), catalase (CAT), and glutathione peroxidase (GPX), were found from previous genomewide association studies (GWAS). Qualified SNPs strongly related to oxidative stress–related biomarkers were selected through a rigorous screening process. As the main method, the inverse variance weighted (IVW) was employed for assessing the causal link between oxidative stress–related biomarkers and the risk of CSVD. Leave-one-out analysis was utilized to measure whether the outcome was influenced by any individual SNP correlated to oxidative stress–related biomarkers. The reverse causality was assessed via reverse MR analysis. The estimates were subject to an odds ratio (OR) with a 95% confidence interval (CI).

Results

The results from IVW revealed that uric acid was causally linked to the increased risk of lacunar stroke (OR = 1.181, 95% CI: 1.042–1.339). There was a causal association between total bilirubin and decreased risk of WMH (OR = 0.984, 95% CI: 0.974–0.994). The scatter plot demonstrated that higher uric acid was positively related to the increased risk of lacunar stroke, and elevated levels of total bilirubin were causally correlated with the reduced risk of WMH. Leave-one-out analysis indicated that there was no single SNP that could affect the causal link between uric acid and lacunar stroke, as well as the causal relationship between total bilirubin and WMH.

Conclusion

Uric acid levels were causally linked with the increased risk of lacunar stroke, and total bilirubin levels were causally related to the decreased risk of WMH.

Background

Despite guidelines for osteoarthritis management, gaps in delivering recommended treatments persist. Osteoarthritis Management Programs (OAMPs) aim to address gaps, but patient perceptions of this care model remain unclear.

Methods

This mixed-methods study evaluated feedback on patient-centered, guideline-adherent care provided by a multidisciplinary team at an American university-based OAMP. Adult patients with visits between July 1, 2017, and January 15, 2021, were categorized into groups by visit number: 1, 2–3, and 4+. Seventy patients randomly selected per group were sent a mailing containing the revised OsteoArthritis Quality Indicator (OA-QI) questionnaire assessing receipt of guideline-recommended care and an interview invitation regarding OAMP experiences. Semistructured interviews were conducted in-person or via telephone.

Results

Of the 953 eligible patients, most were female (72.6%) with an average age of 62.1 years (±10.8) and a mean BMI of 40.9 (±10.0). The 210 patients who were sent the study mailing were similar: 74.8% female, age 63.0 (±1.45), and BMI 40.7 (±1.33). Fifty-nine patients completed the OA-QI, with an overall mean pass rate (care items achieved divided by care items eligible) of 77.5% (SD 17.1%). Pass rates of ≥ 80% were reported by 50.0% of patients with one visit, 59.1% with 2–3 visits, and 52.0% with 4+ visits. Of the 17 interviewees, 16 (94.1%) identified at least one barrier to OA management, predominantly poor social support and comorbid conditions. Fifty-three percent endorsed nonsurgical osteoarthritis management, and 41.2% reported increased knowledge and confidence in self-management. Patient characteristics remained consistent across visit frequencies, with no significant differences among surveyed or interviewed patients.

Conclusions

This OAMP was designed to bridge gaps between recommended and received care. The overall OA-QI pass rate of 77.5% surpassed rates reported by other studies. Interviews indicated improvements in knowledge and attitudes toward nonsurgical OA management; however, identified barriers to care necessitate adjustments to care delivery.

Background

Post-COVID syndrome (PCS) is a condition that occurs after COVID-19 infection that lasts for more than three months and adversely affects the autonomic nervous system (ANS). The aim of this study was to investigate and compare the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS in fatigue in individuals with PCS.

Methods

Forty-two patients (20 male, 22 female) with PCS participated in this study. The severity of fatigue was assessed with the fatigue severity scale (FSS). Heart rate variability (HRV) was measured in participants at baseline and after taVNS. The participants were randomly divided into two groups (taVNS and sham taVNS). taVNS was applied for 20 consecutive days for 30 min each (10 Hz, 300 μs).

Results

The groups were similar in FSS and HRV at baseline (p > 0.05). After the intervention, FSS decreased in taVNS (p = 0.018) and sham taVNS (p = 0.036). RMSSD increased in taVNS (p = 0.010), with no change in sham taVNS (p > 0.05) from baseline to after treatment. Stress index showed no change in both groups (p > 0.05). PNS index increased in taVNS (p = 0.007) and sham taVNS (p = 0.049). The SNS index and low frequency (LF) power decreased in taVNS (p = 0.001, p = 0.017, respectively), with no change in sham taVNS (p > 0.05). High frequency (HF) power showed no change within groups (p > 0.05). LF/HF decreased in taVNS (p = 0.002), with no change in sham taVNS (p > 0.05). Pre- and Post-tests showed taVNS was more effective than sham taVNS in decreasing FSS (p = 0.022) and LF power (p = 0.029), in increasing PNS index (p = 0.016). There was a difference in HF power between groups after treatment (p = 0.042).

Conclusion

Both taVNS and sham taVNS were effective in reducing the severity of fatigue, with sham taVNS being superior to taVNS. The observed effect size was smaller than anticipated. This suggests that larger-sample-size studies are required to verify these results.

Trial Registration: ClinicalTrials.gov identifier: NCT05679505.

Background

Gastric cancer (GC) represents one of the leading malignancies globally. Although notable progress has been achieved in diagnostic and therapeutic approaches, the prognosis of advanced GC patients remains unsatisfactory. Recent studies suggest that Glia maturation factor beta (GMFB) participates in cancer progression; however, the precise function and clinical relevance of GMFB in GC are not fully elucidated.

Methods

GMFB expression was assessed utilizing publicly available databases and further confirmed through immunohistochemistry (IHC) analysis in GC tissues. Associations between GMFB expression and multiple clinicopathological parameters were investigated. Survival outcomes were analyzed using Kaplan–Meier (KM) methods to evaluate GMFB’s prognostic significance. In order to investigate biological functions, GMFB expression was reduced in AGS and HGC-27 GC cells, subsequently evaluating alterations in proliferation, migration, invasion, and processes related to epithelial-mesenchymal transition (EMT). Functional experiments were performed to assess the biological effects of GMFB downregulation.

Results

GMFB expression exhibited a significant increase in GC cell lines and tissues when contrasted with their normal counterparts. Elevated expression levels of GMFB showed a significant correlation with advanced tumor stage, lymph node metastasis (LNM), and a poor prognosis. The KM survival curves indicated a significant association between increased GMFB levels and a decrease in both progression-free interval (PFI) and disease-free interval (DFI), with p values less than 0.001 for both measures. The downregulation of GMFB significantly inhibited the proliferation of GC cells and diminished both migration and invasive capabilities. Moreover, the inhibition of GMFB expression led to downregulation of EMT-associated proteins, including N-cadherin, vimentin, SLUG, and SNAIL, along with upregulation of the epithelial marker E-cadherin, suggesting that GMFB may play a role in tumor progression by enhancing EMT.

Conclusion

GMFB is overexpressed in GC, contributing to tumor growth, migration, and EMT processes. GMFB represents a promising prognostic indicator and potential therapeutic target for GC.