American journal of translational research最新文献

Objectives: This study investigated the expression, clinical relevance, and functional role of signal sequence receptor 1 (SSR1) in liver hepatocellular carcinoma (LIHC). SSR1's potential as a diagnostic marker and its impact on tumor progression was assessed through multi-platform data analysis and in vitro functional assays.

Methodology: Expression data from The Cancer Genome Atlas (TCGA), UALCAN, Oncomine, TIMER2.0, and Human Protein Atlas (HPA) were analyzed to assess SSR1 mRNA and protein expression in LIHC. Clinical correlations with tumor stage, race, gender, age, weight, and nodal metastasis were examined using UALCAN. Promoter methylation, mutation frequency, and prognostic significance were evaluated using UALCAN and OncoDB. Gene set enrichment analysis (GSEA) was conducted to identify pathways enriched in high SSR1 expression. Finally, real-time quantitative polymerase chain reaction (RT-qPCR), proliferation, colony formation, and wound healing assays were performed in QGY-7703 cell lines to validate the SSR1 function.

Results: SSR1 was significantly upregulated in LIHC tissues across multiple databases. Promoter hypomethylation was identified as a potential mechanism for this upregulation. High SSR1 expression correlated with worse overall survival and advanced tumor stages. Functional assays revealed that SSR1, SSR2, and SSR3 knockdown in LIHC cells significantly reduced cell proliferation and colony formation while enhancing migratory capacity.

Conclusion: SSR1 was overexpressed in LIHC and is associated with poor prognosis. It plays a critical role in promoting LIHC cell proliferation and survival, suggesting its potential as a diagnostic marker and therapeutic target.

Objective: To explore the applicability of the Caprini Risk Assessment Scale in burn patients for evaluating the risk of deep vein thrombosis (DVT).

Methods: A retrospective case-control study was conducted involving 278 burn patients from March 2021 to March 2023, with an additional independent test set of 119 patients for external validation. Patients were stratified into DVT and non-DVT groups based on the DVT incidence within one month after burn. The Caprini Risk Assessment Scale was employed to calculate scores and determine risk factors. Multivariate logistic regression analyses identified significant risk factors, and receiver operating characteristic (ROC) curves evaluated the model's predictive power.

Results: The mean Caprini score was significantly higher in the DVT group (6.61 ± 2.64) compared to the non-DVT group (4.89 ± 2.36; P < 0.001). Key risk factors included older age, increased body mass index (BMI), and a personal or family history of thrombosis. DVT patients were more prone to higher Caprini scores and classified as 'very high risk'. Logistic regression demonstrated a positive correlation between Caprini scores, risk stratification, and DVT incidence (β = 0.284, OR = 1.329; β = 0.466, OR = 1.594, respectively). The predictive model displayed strong discriminatory power, with an area under the curve (AUC) of 0.853 in the training set and 0.937 in the test set.

Conclusion: The Caprini Risk Assessment Scale is an effective tool for predicting DVT risk in burn patients, aiding in risk stratification and targeted prophylaxis.

Background: Acute pulmonary embolism (PE) is a life-threatening condition requiring effective anticoagulation therapy. Rivaroxaban, a direct oral anticoagulant, offers advantages over warfarin, yet individual patient responses vary. This study examined the efficacy of rivaroxaban compared to warfarin and evaluated vascular endothelial markers as predictors of anticoagulant efficacy.

Methods: We conducted a retrospective cross-over cohort study involving 295 patients with acute PE, comparing rivaroxaban (n = 158) and warfarin (n = 137) treatments. Clinical efficacy was assessed based on symptomatic improvement and imaging results. Vascular endothelial markers, including soluble thrombomodulin (sTM), circulating endothelial cells (CEC), and endothelin-1 (ET-1), were examined for their predictive capability in treatment outcomes, then the data of 97 additional patients were used for external validation.

Results: Patients who received rivaroxaban showed higher overall treatment response (93.04%) compared to those who took warfarin (74.45%; P < 0.001), and greater improvement in arterial partial pressure of oxygen (PaO₂; P = 0.003). Rivaroxaban significantly altered coagulation parameters such as prothrombin time (PT) and international normalized ratio (INR). In addition, elevated sTM and reduced CEC were found to be associated with poorer anticoagulation outcomes. The areas under the receiver operating characteristic curve (AUCs) for predicting efficacy using vascular endothelial markers were 0.913 in the training cohort and 0.888 in the external validation cohort, respectively.

Conclusion: Rivaroxaban was more effective than warfarin in treating acute PE, with specific vascular endothelial markers serving as promising predictors of therapeutic response.

Objective: Limited data are available on the effects of combined and intravenous or oral chemotherapy on the survival of patients who have undergone D2 gastrectomy for cancer.

Methods: This study involved 1314 patients who participated in a trial that followed D2 gastrectomy with adjuvant or neoadjuvant chemotherapy.

Results: Following propensity score matching (PSM), the results indicated that contrary to expectations, combined chemotherapy administration was associated with poorer overall survival (OS) and progression-free survival (PFS) at the 5-year mark for stage II gastric cancer, with log-rank P values of 0.005 for OS (83.6% vs. 68.8%) and 0.005 for PFS (71.6% vs. 61.5%). Significant differences were observed in the recurrence rate (P < 0.001) and local-regional recurrence (P = 0.009), although no significant difference was found for distant metastasis (P = 0.146). For stage III gastric cancer, the Kaplan-Meier survival curves showed that the combination of oral and intravenous chemotherapy was inferior to single-modality chemotherapy for PFS (P = 0.006). However, it did not differ significantly from single therapy in OS (P = 0.257). Notable discrepancies were evident in the recurrence rate (P < 0.001), distant metastasis (P < 0.001), and local-regional recurrence (P = 0.003).

Conclusions: The findings suggest that the concurrent use of oral and intravenous chemotherapy after D2 gastrectomy does not enhance the prognosis for gastric cancer patients compared to using either modality alone. Instead, it appears to increase the risk of disease progression for stage III patients and the likelihood of recurrence for both stages II and III of gastric cancer.

Objective: To evaluate the effect of metoprolol combined with spironolactone on cardiac function in patients with coronary heart disease (CHD) complicated by heart failure.

Methods: The study involved 123 patients with CHD and heart failure treated at Anqing Shihua Hospital of Nanjing Drum Tower Hospital Group between February 2022 and May 2024. After applying the inclusion and exclusion criteria, 100 cases were finally selected. The patients were divided into two groups: the control group (CG, 46 patients), receiving metoprolol monotherapy, and the research group (RG, 54 patients), receiving metoprolol combined with spironolactone. Cardiac function indicators, including left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESd), and left ventricular end-diastolic diameter (LVEDd), were assessed before and after treatment. Additionally, changes in B-type natriuretic peptide (BNP) and C-reactive protein (CRP), cardiac index, and cardiac output were analyzed. The clinical treatment efficacy was also analyzed. Logistic regression analysis was used to identify the risk factors influencing treatment outcomes.

Results: Following treatment, both groups showed significant improvements in LVEF (P<0.05) and reductions in LVESd and LVEDd (P<0.05). The RG demonstrated significantly greater improvements in LVEF and more pronounced reductions in LVESd and LVEDd compared to the CG (P<0.05). BNP and CRP levels significantly decreased in both groups (P<0.05), with the RG showing significantly lower levels than the CG (P<0.05). Both cardiac index and cardiac output increased significantly in both groups (P<0.05), with the RG demonstrating notably higher values than the CG (P<0.05). The total effective rate was 69.56% in the CG, significantly lower than 90.74% in the RG (P<0.05). Logistic regression identified age, duration of heart failure, and treatment method as independent risk factors influencing the treatment outcomes (all P<0.05).

Conclusion: Metoprolol combined with spironolactone significantly improves cardiac function, reduces inflammation, and enhances cardiac performance in patients with CHD complicated by heart failure.

Introduction: Inflammatory Bowel Disease (IBD), encompassing Crohn's disease and ulcerative colitis, presents significant clinical challenges due to its heterogeneous nature and complex etiology. Recent advancements in biomedical research have enhanced our understanding of IBD's genetic, microbial, and biochemical aspects. However, persistent issues in clinical management, including treatment non-response, surgical interventions, and diagnostic uncertainties, underscore the need for more targeted approaches. This review examines the convergence of artificial intelligence (AI) and precision medicine (PM) in IBD management. By leveraging AI's capacity to analyze complex, multi-dimensional datasets, this emerging field offers promising applications in improving diagnostic accuracy, predicting treatment responses, and forecasting disease progression, potentially transforming IBD patient care.

Method: The systematic review (SR) was conducted by searching the following databases: PubMed, PubMed PMC, BVS, Scopus, Web of Science, Embase, Cochrane, and ProQuest up to February 2024. Studies that employed AI in IBD applied to precision medicine were included.

Results: 139 studies on applying AI in precision medicine for IBD were identified. Most studies (>70%) were published after 2020, indicating a recent surge in interest. The AI applications primarily focused on diagnosis, treatment response prediction, and prognosis. Machine learning algorithms were predominantly used, particularly random forest, logistic regression, and support vector machines. Omics data were frequently employed as predictors, especially transcriptomics and microbiome analyses. Studies demonstrated good predictive performance across all three areas, with median AUC values ranging from 0.85 to 0.90.

Conclusion: AI applications in IBD show promising potential to enhance clinical practice, particularly in disease prognosis and predicting treatment response. However, clinical implementation requires further validation through prospective studies. Future research should focus on standardizing protocols, defining clinically significant outcomes, and evaluating the efficacy of these tools.

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) compared to NAC combined with immune checkpoint inhibitors (ICI) in patients with muscle-invasive bladder cancer (MIBC). Propensity score matching (PSM) was employed to assess the impact of these two treatment regimens on the pathological complete response rate (pCR) and overall survival (OS).

Methods: A retrospective analysis was conducted on 320 MIBC patients treated at the Cancer Hospital affiliated to Sun Yat-sen University Gansu Hospital between January 2017 and June 2022. Patients were categorized into the NAC group (n=194) and the NAC+ICI group (n=126) based on their treatment regimens. After PSM, 154 patients were included, with 77 in each group. Baseline characteristics, clinical efficacy, and prognosis were analyzed using various statistical methods.

Results: Before PSM, significant differences were observed between the groups in baseline characteristics, including tumor diameter, tumor number, and adjuvant treatment (all P<0.05). After PSM, these differences were no longer statistically significant (all P>0.05). The NAC+ICI group demonstrated a significantly higher pCR rate both before and after PSM (both P<0.001). Similarly, pathological downstaging rates were higher in the NAC+ICI group before and after PSM (both P<0.001). However, there was no significant difference in disease control rates between the two groups before (P=0.057) and after PSM (P=0.240). Logistic regression analysis identified the treatment regimen (before PSM: P<0.001, OR=0.161; after PSM: P<0.001, OR=0.141) and complications (before PSM: P=0.005, OR=2.339; after PSM: P=0.019, OR=2.753) as independent risk factors for pCR. Cox regression analysis revealed that age (before PSM: P<0.001, HR=1.059; after PSM: P=0.011, HR=1.066), pretreatment T stage (before PSM: P<0.001, HR=2.342; after PSM: P<0.001, HR=3.244), tumor diameter (before PSM: P=0.005, HR=1.810; after PSM: P=0.025, HR=2.077), and treatment outcome (before PSM: P<0.001, HR=1.722; after PSM: P=0.020, HR=1.444) were independent prognostic factors for OS.

Conclusion: NAC combined with ICI significantly improves pCR and pathological downstaging rates in MIBC patients. Independent prognostic factors affecting OS include age, pretreatment T stage, tumor diameter, and treatment outcome.

Objective: This study aimed to assess the efficacy and safety of sacral nerve root magnetic stimulation (SNRMS) combined with solifenacin in female patients with overactive bladder (OAB) symptoms.

Methods: A total of 183 female patients with OAB symptoms were prospectively randomized into 2 groups. Ninety-two patients in the combination group accepted SNRMS and solifenacin therapy and 91 patients serving as control accepted only solifenacin therapy. The lower urinary tract symptoms, OAB questionnaire (OAB-q) health-related quality of life (HRQoL), symptom bother score, and overactive bladder syndrome score (OABSS) were compared between the two groups at the end of the second, fourth, and eighth weeks.

Results: The incidence of lower urinary tract symptoms, including urgency, frequent urination, and incontinence episodes, was significantly lower in the fourth and eighth weeks in patients of the combination treatment group than those in the solifenacin group (P < 0.05). The incidence of drug-related adverse events in the two groups was similar, with no statistically significant difference (P > 0.05). The OAB-q HRQoL score in the combination group was significantly higher than that in the solifenacin group between the fourth and eighth weeks (P < 0.05). Meanwhile, the OAB-q symptom bother score and OABSS were both lower in the combination group than those in the solifenacin group from the fourth to eighth weeks (P < 0.05).

Conclusions: The combination therapy of SNRMS and solifenacin demonstrated significant improvements over solifenacin monotherapy in reducing OAB symptoms in female patients, providing a higher QoL without increasing bothersome adverse effects.

Objective: To explore the therapeutic effects of Zhuyang Tongbian Decoction (ZTD) on vasoactive intestinal peptide (VIP) and 5-hydroxytryptamine receptor (5-HTR) in colon tissues, intestinal flora, and fecal metabolites in mice with functional constipation (FC).

Methods: A total of 36 BALB/c mice were divided into six groups: control, model, positive (Cisapride), and ZTD groups with three dosages (1.5 g/mL, 3 g/mL, and 6 g/mL). All mice, except those in the control group, were induced with FC by gavage using the compound diphenoxylate. After establishing the model, each group received the respective treatments by gavage for two weeks. The laxative effect was evaluated by comparing changes in body weight, fecal weight, fecal water content, and the percentage of carbon powder propulsion in the small intestine. Immunohistochemistry was used to assess the distribution and expression of VIP and 5-HTR in proximal colon tissues. Additionally, 16S rRNA sequencing and liquid chromatography with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) non-targeted metabolomics analysis were used to examine the effects of ZTD on intestinal flora composition and metabolites in FC mice.

Results: ZTD treatment not only alleviated FC symptoms but also increased the number of VIP and 5-HTR-positive cells in colon tissues. Furthermore, ZTD improved the diversity and abundance of intestinal flora, significantly increasing the relative abundance of Prevotellaceae, Bacteroidales_S24-7_group, Ruminococcaceae, and Roseburia while reducing the abundance of Proteobacteria, Desulfovibrionaceae, Rikenellaceae, Porphyromonadaceae, and Erysipelotrichaceae. In terms of metabolites, ZTD significantly elevated the levels of deoxyadenosine and adenine, while significantly lowering the levels of L-leucine, L-threonine, succinate, tyramine, L-tyrosine, and dopamine.

Conclusions: This study provides a theoretical basis for the treatment of FC with ZTD. ZTD increased levels of the intestinal neurotransmitters VIP and 5-HTR and promoted the colonization of beneficial bacteria, including the dominant butyric acid-producing bacterium Roseburia. Additionally, ZTD reduced fecal dopamine levels, indicating its value as a therapeutic approach for FC.

Objectives: To investigate the efficacy of biofeedback electrical stimulation combined with early intensive rehabilitation training on cerebral blood circulation, neurological function recovery, motor performance, and self-care abilities in stroke patients.

Methods: A retrospective analysis was conducted on 120 stroke patients admitted to the Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University from September 2021 to October 2023. Patients were divided into an observation group (n=60) receiving the combined treatment and a control group (n=60) receiving standard rehabilitation. Efficacy was evaluated through the analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels, as well as assessments of several clinical variables, including Peak Systolic Velocity (PSV), Mean Velocity (Vm), Resistance Index (RI), Fugl-Meyer Assessment (FMA), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Berg Balance Scale (BBS), National Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), and Stroke-Specific Quality of Life Scale (SS-QOL). Measurements were taken before treatment and upon completion.

Results: The findings revealed that the combination of electrical stimulation with early rehabilitation exercises significantly improved cerebral blood flow in stroke patients. This approach accelerated the recovery of neurological functions, enhanced motor skills, and improved self-care capabilities among participants. The results demonstrated substantial treatment benefits alongside a favorable safety profile.

Conclusions: The integration of biofeedback electrical stimulation with intensive rehabilitation exercises significantly enhances neurological and motor function recovery in stroke patients while promoting better self-care skills, all within a safe treatment framework. This approach warrants further clinical research and potential implementation.