American journal of translational research最新文献

Objective: To evaluate the clinical efficacy of endocrine therapy for prostate cancer and analyze risk factors for treatment-related cognitive dysfunction.

Methods: A retrospective study was conducted involving 100 prostate cancer patients receiving endocrine therapy and 100 non-recipients. Quality of life, urinary symptoms, and cognitive function were assessed. Patients were categorized into cognitive dysfunction (n=38) and non-dysfunction (n=62) groups based on post-treatment assessment. Univariate and multivariate analyses were used to identify influencing factors, and a predictive model was developed.

Results: The endocrine therapy group showed significantly better quality of life and urinary symptom scores (all P < 0.05), though the 5-year survival rate was lower than that of the control group (72.4% vs 82.7%). Cognitive impairment incidence was 38%. Risk factors included older age, lower education, lower Montreal Cognitive Assessment (MoCA) scores, and higher Prostate-Specific Antigen (PSA), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores (all P < 0.05). Multivariate analysis confirmed MoCA, age, SAS, and SDS as independent predictors. The predictive model demonstrated high discriminative ability (AUC=0.903).

Conclusion: Endocrine therapy improves quality of life and urinary symptoms in prostate cancer patients but is associated with cognitive dysfunction. A model incorporating MoCA, age, and psychological scores effectively predicts cognitive impairment risk, enabling targeted intervention.

Objective: To evaluate the treatment efficacy of low-temperature plasma radiofrequency ablation (LTP-RFA) in patients with early glottic carcinoma (EGC).

Methods: A total of 80 EGC patients were retrospectively selected and divided into a control group (standard laryngofissure) and a research group (LTP-RFA) based on their treatment methods. Surgery-related indicators, visual analogue scale (VAS) and mucosal recovery scores, efficacy, serum indices, voice acoustics (amplitude perturbation, fundamental frequency perturbation, harmonic-to-noise ratio), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTCQLO-C30) scores, complications, and postoperative recurrence were compared between the two groups.

Results: Compared to the control group, patients in the LTP-RFA group demonstrated markedly shorter surgery time, less intraoperative blood loss, and reduced length of hospital stay. In addition, postoperative VAS score, mucosal recovery score, and the total complication rate were all lower in the research group, with a higher overall effective rate. The research group also exhibited greater reductions in post-treatment serum biomarker levels (e.g., matrix metalloproteinase-9 (MMP-9), nitric oxide (NO), or vascular endothelial growth factor (VEGF)), better improvements in acoustic parameters (e.g., amplitude perturbation, fundamental frequency perturbation, and harmonic-to-noise ratio) than the control group, along with higher total EORTCQLO-C30 scores. The recurrence rate was equivalent in the two groups.

Conclusion: LTP-RFA is an effective treatment for EGC, offering advantages in improving therapeutic efficacy, voice acoustics, as well as reducing postoperative complications.

Objectives: This study evaluates the impact of sacubitril/valsartan on cardiac structure and function in post- acute myocardial infarction (AMI) heart failure (HF) patients over 65 years.

Methods: A retrospective analysis was conducted on 204 HF patients over 65 years who experienced AMI between January 2018 and December 2023. Patients were divided into two groups: sacubitril/valsartan treatment group (n = 103) and enalapril treatment group (n = 101). Baseline characteristics were comparable between the two groups. Echocardiographic evaluations, six-minute walk tests, treatment effects, adverse reactions, and patient satisfaction were assessed over a one-year follow-up period.

Results: The sacubitril/valsartan group had bigger decreases in NT-proBNP (P < 0.001) and cTnI (P = 0.030). The sacubitril/valsartan group demonstrated significant improvements in left ventricular ejection fraction (LVEF) (P = 0.002), reduced left ventricular end-diastolic volume (LVEDV) (P = 0.019), and left ventricular end-systolic volume (LVESV) (P = 0.002) when compared to the enalapril group. A substantial increase in six-minute walk test distance was observed in the sacubitril/valsartan group (P = 0.013). The treatment was significantly more effective in the sacubitril/valsartan group compared to the enalapril group (51.46% v.s. 30.69%, P = 0.011). Patient satisfaction was also higher in the sacubitril/valsartan group (P = 0.043).

Conclusion: Sacubitril/valsartan shows superior efficacy over enalapril in improving cardiac structure, function, exercise capacity, and patient satisfaction in elderly post-AMI HF patients, as evidenced by greater improvements in cardiac function and more pronounced reduction in stress-related biomarkers.

Objective: The molecule known as Programmed death-ligand 1 (PD-L1) exerts an inhibitory effect on immune system reactions and promotes cancer progression. Its prognostic role in small cell lung cancer (SCLC) remains less defined than in non-small cell lung cancer. This study aimed to evaluate PD-L1 expression and its prognostic value in SCLC, comparing detection by immunohistochemistry (IHC) and reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Methods: PD-L1 expression was assessed in paired tumor and non-tumor tissues from 66 SCLC patients using IHC and RT-qPCR. IHC positivity was defined as membrane staining in >5% of tumor cells. Associations with clinicopathological factors were examined by Fisher's exact test. Survival analysis employed Kaplan-Meier curves and log-rank tests. Univariate and multivariate Cox regression identified independent prognostic factors.

Results: IHC analysis showed PD-L1 positivity in 34/66 patients. RT-qPCR revealed significantly higher PD-L1 mRNA levels in tumor versus non-tumor tissues (P<0.01). Both IHC positivity and high mRNA levels were associated with larger tumor size, metastasis, and advanced clinical stage (all P<0.05), but not with age, gender, or smoking/drinking history. Patients with PD-L1-positive IHC staining or high PD-L1 mRNA exhibited significantly worse 5-year overall survival (P<0.05), with IHC showing stronger prognostic discrimination. Multivariate analysis confirmed IHC positivity (HR=2.45, P=0.004) and high mRNA level (HR=2.12, P=0.012) as independent predictors of poor survival.

Conclusion: PD-L1 expression is associated with aggressive clinicopathological features and independently predicts poor survival in SCLC. IHC appears to be a more sensitive detection method than RT-qPCR for prognostic assessment.

Background: Gap junction protein 5 (GJB5) has been associated with tumorigenesis; however, its exact role in pancreatic adenocarcinoma (PAAD) remains unclear. This study investigates GJB5's expression, its functional roles in tumor progression, and its prognostic significance in PAAD.

Methods: This study used multiple bioinformatics tools, including Tissue Infiltrating Microenvironment Estimation Resource 2, University of Alabama at Birmingham Cancer, Tumor Immune System Interaction Database, Gene Expression Profiling Interactive Analysis 2, and cBioPortal. These tools were used to analyze GJB5 expression, its correlation with immune cell infiltration, and its potential as a prognostic biomarker in PAAD. Functional assays, including cell counting kit-8, colony formation, wound healing, and transwell assays, were performed to investigate the impact of GJB5 on PAAD tumor cell behaviors, including proliferation, migration, and invasion. Additionally, pathways associated with GJB5 and its interactions with the tumor microenvironment were explored.

Results: GJB5 was significantly overexpressed in PAAD tissues compared to adjacent normal tissues. Promoter hypomethylation, rather than somatic mutation, was identified as the primary mechanism driving GJB5 upregulation. Survival analysis and Cox regression models indicated that upregulated GJB5 expression is an independent prognostic factor for poor survival in patients with PAAD. Furthermore, GJB5 expression was positively correlated with immune cell infiltration in the PAAD microenvironment. Functional assays exhibited that silencing GJB5 reduced cell proliferation, migration, and invasion in PAAD cell lines.

Conclusions: GJB5 is a significant prognostic biomarker for PAAD and a potential therapeutic target for reversing tumor progression, providing novel strategies for PAAD treatment.

Brachial plexus block anesthesia is widely utilized for upper limb surgical procedures in clinical settings. The diffusion of local anesthetics within the intermuscular sulcus structure can lead to nerve paralysis. However, we report an exceptionally rare case of concurrent extensive neural blockade, with a spread far beyond expected boundaries, which carries significant clinical cautionary implications. This case report described a previously healthy patient who successfully underwent arthroscopic rotator cuff repair on the right shoulder under general anesthesia combined with a brachial plexus block. Following an ultrasound-guided intermuscular groove approach for brachial plexus block and superficial cervical plexus block, the patient developed numbness and reduced muscle strength in the right upper and lower limbs, along with unresponsiveness to painful stimuli. This paralysis lasted for at least 48 hours. Postoperative cranial computerized tomography (CT) and cervical X-ray showed no significant abnormalities. No neurological sequelae were observed after the complete resolution of the anesthetic effect. Necessary but limited tests and examinations were performed to establish a differential diagnosis, effectively excluding cerebral infarction, spinal disorders, peripheral vascular and nerve diseases, electrolyte abnormalities, and hysteria. While it is hypothesized that local anesthetics may contribute to lower limb paralysis, the specific mechanism by which these agents affect the nerves in this region remains unclear and requires further investigation.

Objective: To investigate the protective effects and underlying mechanisms of tanshinone IIA in preventing septicemia acute kidney injury (SA-AKI).

Methods: Mice were pretreated with tanshinone IIA via intraperitoneal injection, followed by lipopolysaccharide (LPS) administration to induce SA-AKI. Hematoxylin-eosin (HE) staining was used to assess renal tissue injury to confirm successful model establishment. In vitro, HK2 cells were treated with LPS and/or tanshinone IIA. Differentially expressed genes (DEGs) between the LPS and tanshinone IIA + LPS groups were identified via high-throughput sequencing. qPCR was performed to validate mRNA expression of key DEGs. Protein expression in mouse kidney and HK2 cells was analyzed using immunohistochemistry and western blot.

Results: Mice in the SA-AKI model demonstrated severe renal damage, with elevated levels of serum creatinine and urea nitrogen, as well as increased apoptosis and glycogen accumulation. Tanshinone IIA pretreatment significantly alleviated these pathological changes. Flow cytometry confirmed that LPS induced HK2 cell apoptosis, which was attenuated by tanshinone IIA. Transcriptomic analysis revealed 121 upregulated and 65 downregulated genes. Western blot showed that LPS increased JNK, p38, NLRP3 and Caspase-1 expression, and decreased DUSP10 and ALDH2 expression, while tanshinone IIA pretreatment reversed these effects. Similarly, immunohistochemistry and western blot analyses demonstrated elevated contents of KIM-1, NLRP3, JNK and Caspase-1, and reduced DUSP10 and ALDH2 in SA-AKI mice.

Conclusion: Tanshinone IIA exerts a protective effect against SA-AKI by mitigating inflammation and apoptosis. Mechanistically, these effects appear to be mediated through DUSP10 and modulation of the JNK/P38/NLRP3 pathway. These findings suggest that tanshinone IIA might be a potential therapeutic strategy for SA-AKI.

Objective: To characterize the relationships between in vivo confocal microscopy (IVCM) - derived corneal immune - neural metrics, and systemic cytokines and ocular surface findings in Sjögren's syndrome-associated dry eye disease (SS-DED), and to identify variables independently associated with SS-DED status.

Methods: A retrospective case - control study was conducted (Jan 2019 - Jan 2022), including 120 SS-DED patients and 88 healthy controls. Corneal dendritic cell density (DCD), inflammatory cell density (ICD), and nerve fiber density (NFD) were quantified by IVCM. Tear break-up time (BUT), corneal fluorescein staining (FL), Schirmer test, and Ocular Surface Disease Index (OSDI) were assessed using standard protocols. Variables independently associated with SS-DED were identified using multivariable logistic regression, and their discrimination performance was evaluated using receiver operating characteristic (ROC) analysis.

Results: Compared to controls, SS-DED patients showed significantly higher levels of IL-1β, IL-6, TNF-α, DCD, and ICD, and lower NFD levels (all P<0.001). DCD correlated positively with IL-1β, BUT, FL, and OSDI (P<0.05), while NFD correlated negatively with BUT and FL (P<0.001). ICD positively correlated with IL-1β, IL-6, TNF-α, and DCD (all P<0.001). Multivariate regression analysis identified IL-1β (OR=1.249, P<0.001), OSDI (OR=1.074, P=0.033), DCD (OR=1.411, P=0.002), and ICD (OR=1.006, P=0.018) as independent factors associated with SS-DED. Among them, DCD demonstrated the highest discriminative power (AUC=0.886; specificity 98.75%; sensitivity 65.00%).

Conclusion: Elevated IL-1β, OSDI, DCD, and ICD levels are independent risk factors for SS-DED. Among these factors, DCD exhibited superior predictive performance over the others and may be a biomarker for SS-DED diagnosis and disease monitoring.

Objective: To investigate the effects of complete revascularization on oxidative stress, blood pressure control, and prognosis in patients with acute myocardial infarction (AMI).

Methods: Clinical data from 80 AMI patients were retrospectively analyzed. Based on the SYNTAX Revascularization Index (SRI), patients were classified into the complete revascularization group (SRI=100%, n=31), partial revascularization group (SRI 50-99%, n=27), and low revascularization group (SRI<50%, n=22). Postoperative oxidative stress markers (malondialdehyde, MDA; angiotensin converting enzyme, ACE; and superoxide dismutase, SOD), myocardial injury marker (cardiac Troponin I, cTnI), and ambulatory blood pressure parameters were compared among groups. Their correlations were analyzed, and the predictive value of SRI for major adverse cardiovascular events (MACE) was evaluated.

Results: One month after surgery, the complete revascularization group exhibited significantly lower MDA than the partial and low revascularization groups, higher SOD, and lower ACE and cTnI levels (all P<0.001). Six months postoperatively, the complete revascularization group showed improvements in 24 h SBP, 24 h SBP-SD and nocturnal blood pressure decline rate (all P<0.01). The incidence of MACE was significantly lower in the complete revascularization group (6.45% vs. 36.73%, P=0.002). Logistic regression showed that SRI was an independent protective factor for MACE (OR=0.119, 95% CI: 0.025-0.557, P=0.007). ROC curve analysis indicated its predictive value for MACE with an AUC of 0.835 and an optimal cut-off value of 69.360%.

Conclusion: Complete revascularization improves blood pressure stability and reduces MACE risk in AMI patients by alleviating oxidative stress. Achieving an SRI above 69.360% can be considered a clinical target.

Diabetic myocardial fibrosis (DMF) is a prominent pathological process that leads to the progression of diabetic heart disease, and yet the underlying mechanisms have not been properly clarified. Recently, a new paradigm called Micro Zhēngjiǎ lesion has been implicated, with microstructural changes in the myocardial capillaries being indicated as critical factors in the development of diabetic fibrosis. The purpose of the review is to investigate the mechanistic basis of the Micro Zhēngjiǎ lesion in DMF and its implications across tissue, cellular, and molecular levels. This article summarizes findings from histological and imaging studies, which show the structural and functional impairments of the myocardial extracellular space, as well as dysregulation of fibrosis-related signaling pathways, in the diabetic heart. Moreover, potential treatment interventions are reviewed, especially Huoxue-Tongluo therapy. This approach, which aims to activate blood circulation and dredge collaterals, combines traditional Chinese medicine with modern pharmacological principles to reverse the development of DMF. By targeting major inflammatory mediators, improving microcirculation, and regulating fibroblast activation, Huoxue-Tongluo therapy has the potential to be used as an alternative or complementary approach to conventional therapy. The review proves the translational potential of the given therapeutic paradigm and suggests future research directions to investigate the multifaceted interplay of microstructural lesions, metabolic dysfunction, and fibrosis in the diabetic heart in depth.