American journal of translational research最新文献

Objective: To retrospectively analyze the effects of Butylphthalide and Sodium Chloride Injection (BP-SC) combined with Argatroban (AG) on neurological deficits and hemorheology in progressive ischemic stroke (PIS) patients.

Methods: A total of 123 PIS patients admitted to our hospital between April 2023 and April 2025 were retrospectively analyzed and divided into two groups according to the different treatment schemes: the control group (n=58; treated with AG) and the research group (n=65; treated with BP-SC and AG). Clinical efficacy, neurological deficits (assessed by the National Institutes of Health Stroke Scale [NIHSS]), neurological function (astrocyte-derived protein S100β, brain-derived neurotrophic factor [BDNF], and neuron-specific enolase [NSE]), hemorheology (fibrinogen [FIB], plasma viscosity [PV], whole blood low-shear viscosity [WBLSV]), vascular endothelial function (endothelin-1 [ET-1] and nitric oxide [NO]), inflammatory factors (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), adverse events (gingival bleeding, subcutaneous ecchymosis, nausea, abdominal distension, and vomiting), the 90-day post-operative modified Rankin Scale (mRS) score were compared between the two groups.

Results: Compared with the control group, the research group demonstrated significantly higher overall effective rate and favorable prognosis rate. The research group also showed greater post-treatment reductions in the NIHSS score and levels of S100-β and NSE, along with a more pronounced elevation in BDNF level, indicating improved neuronal function. Additionally, the combined treatment significantly improved multiple hemorheological indices and endothelial function as evidenced by reduced ET-1 level and elevated NO level. Moreover, levels of hs-CRP, IL-6, and TNF-α were significantly decreased. However, the total incidence of adverse events was comparable between the two groups.

Conclusion: Combined treatment with BP-SC and AG exerts more significant improvements in neurological deficits and hemorheological parameters in PIS patients.

Background: The factors influencing the long-term pulmonary function recovery in survivors of acute respiratory distress syndrome (ARDS) remain unclear.

Methods: We systematically searched PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases for cohort studies published from inception to August 31, 2025. Two researchers independently performed literature screening and data extraction, and the Newcastle-Ottawa Scale was used to assess study quality.

Results: A total of 23 cohort studies involving 5876 patients were included. The meta-analysis revealed that factors associated with poor long-term pulmonary function recovery included: age ≥ 65 years (OR=2.35, 95% CI: 1.98-2.79, P < 0.001), severe ARDS (OR=3.16, 95% CI: 2.64-3.78, P < 0.001), prolonged mechanical ventilation time (OR=1.08 per additional day, 95% CI: 1.05-1.11, P < 0.001), coexisting chronic obstructive pulmonary disease (OR=3.27, 95% CI: 2.45-4.37, P < 0.001), and elevated interleukin-6 levels during the acute phase (SMD=1.24, 95% CI: 0.87-1.61, P < 0.001). The meta-analysis results showed that factors associated with favorable long-term pulmonary function recovery included: early lung-protective ventilation (OR=0.42, 95% CI: 0.33-0.54, P < 0.001), glucocorticoid intervention (OR=0.56, 95% CI: 0.43-0.73, P < 0.001), and initiation of rehabilitation treatment within ≤ 7 days of onset (OR=0.38, 95% CI: 0.29-0.49, P < 0.001). Subgroup analysis of ARDS type indicated that both disease severity and duration of mechanical ventilation influenced prognosis.

Conclusion: Older age, severity of ARDS, prolonged ventilation time, coexisting chronic obstructive pulmonary disease and elevated interleukin-6 levels during the acute phase are the main factors associated with poor long-term pulmonary function recovery in patients with ARDS. Early lung-protective ventilation, glucocorticoid use, and rehabilitation interventions are important protective measures.

In certain clinical scenarios, a single diagnosis may be insufficient or even inadequate to fully explain complex or atypical phenotypes. Herein, we present three pediatric cases diagnosed with dual rare genetic disorders and analyze their medical histories and diagnostic trajectories. A total of nine gene mutations were detected, among which seven were novel, including c.[791T>C];[695G>A] in DNAH1, loss2(EXON:3-5) in SGCB, c.[1A>G] (reported);[1024A>G] (reported) in RARS2, c.[962-1G>T];[592A>T] in KIAA0586, and c.358C>T in IRF2BPL, c.2714C>T in KDM6A.

Objective: To investigate the effects of single low-dose esketamine combined with patient-controlled intravenous analgesia (PCIA) on early postpartum depression symptoms and recovery quality in women undergoing cesarean section.

Methods: This prospective, randomized, controlled study enrolled 136 women scheduled for elective cesarean section, who were randomly assigned in a 1:1 ratio to the study group (esketamine group, n=68) or the control group (placebo group, n=68). In the study group, esketamine (0.2 mg/kg) was intravenously infused for 40 minutes immediately after fetal delivery. In the control group, an equal volume of normal saline was given. Both groups then received PCIA for pain relief maintenance after the operation. The Edinburgh Postnatal Depression Scale (EPDS) scores, Obstetric Quality of Recovery-10 (ObsQoR-10) scores, and postoperative recovery indicators were compared between groups at different time points after surgery.

Results: Compared with the control group, the study group showed significantly lower EPDS scores at postoperative days 2 and 7, higher ObsQoR-10 scores, shorter times to first ambulation, flatus, and breastfeeding, as well as increased breastfeeding frequency within 48 hours (all P<0.05). The incidence of adverse reactions revealed no statistically significant difference (P>0.05).

Conclusion: A single low-dose esketamine combined with PCIA effectively alleviates early postpartum depression symptoms, enhances postoperative recovery in women undergoing cesarean section, and demonstrates good safety and clinical applicability.

Objective: To establish a nomogram model based on bone mineral density (BMD), and radiographic indexes of the proximal femur for predicting hip fracture (HF) risk in osteoporosis patients.

Methods: A total of 120 patients who underwent both orthopedic and lateral view examination from February 2022 to January 2024 were retrospectively collected and screened. They were divided into fracture (n=60) and non-fracture groups (n=60). The recorded parameters included sex, age, femoral intertrochanteric BMD, femoral cortical thickness (FCT), femoral neck length (FNL), hip axis length (HAL) and the hip offset distance (FO). Univariate and multivariate logistic regression analysis were conducted to determine the risk factors for hip fracture in osteoporotic patients. A nomogram model was subsequently constructed. Furthermore, to validate the model's clinical utility, an additional 1-year follow-up was conducted on 40 randomly selected patients.

Results: The fracture group had significantly longer HAL, thinner FCT, and reduced femoral intertrochanteric BMD than the non-fracture group (all P < 0.001). The HAL, FCT and intertrochanteric BMD were the independent risk factors for the hip fracture. The model accurately predicted hip fracture in osteoporosis patients, with an Area under the curve (AUC) of 0.93, sensitivity of 0.86 and specificity of 0.83. During a one-year follow-up of 40 osteoporosis patients, 6 fractures were observed, 5 with a prediction model score > 100 and 1 with a score < 100, further validating the reliability of the predictive model.

Conclusion: The nomogram model has a better prediction ability of hip fracture risk in osteoporosis patients. It provides a theoretical basis for the individualization of the diagnosis and treatment for elderly patients.

Objective: M2 macrophage-derived exosomes (M2-exos) hold promise for patients with bone cancer pain (BCP). This study aimed to investigate the therapeutic effect and related mechanisms of M2-exos in both in vitro and in vivo models of BCP.

Method: RAW 264.7 macrophages were treated with IL-4 to generate M2-polarized macrophages. M2-exos were characterized by transmission electron microscope and Western blotting. A mouse model of BCP was established, and BV2 microglia were activated by lipopolysaccharide stimulation. The effects of M2-exos were evaluated in vitro by coculture with reactive BV2 microglia and in vivo by microinjection into the rostral ventromedial medulla (RVM) of BCP mice. CCK-8 assays, ELISAs, flow cytometry and immunofluorescence were used to determine the effects of M2-exos on microglial activation. The therapeutic effects of M2-exos were evaluated via pain behavior experiments. Bioinformatic analysis and rescue experiments were performed to investigate the mechanisms through which M2-exos affect the progression of BCP.

Results: In vitro, M2-exos administration repolarized microglial toward the anti-inflammatory M2 phenotype in coculture systems. In vivo analysis indicated that microinjection of M2-exos into the RVM region improved neuroinflammation. Notably, miR-216a expression was significantly increased in M2-exos and could be delivered into BV2 microglia. Blockade of miR-216a abolished the therapeutic effects of M2-exos in vitro and in vivo. Mechanistically, miR-216a negatively regulates high mobility group Box 1 protein (HMGB1) expression, further inhibiting Toll-like receptor 4 (TLR4)/NF-κB and inducing M2 microglial polarization, thereby delaying BCP progression.

Conclusion: M2 macrophage-derived exosomal miR-216a could delay BCP progression by targeting HMGB1/TLR4/NF-κB-mediated microglial M2 polarization.

Objective: Dose optimization of ceftazidime-sulbactam (CFP-SUL) and levofloxacin (LVFX) for pneumonia and urinary tract infections in patients with hepatic insufficiency.

Methods: A total of 100 patients were recruited from the First People's Hospital of Chun'an County and Hanchuan People's Hospital between January 2018 and November 2024. It compared two groups, with primary endpoints (successful intention-to-treat, treatment failure, 7-day clinical cure rate, time to cure, symptom improvement), secondary endpoints (reasons for treatment failure, free time (fT) > minimal inhibitory concentration (MIC) target achievement, adverse event incidence), and performed a subgroup analysis.

Results: CFP-SUL's MIC values against bacterial isolates ranged from 16 to 256 mg/L, with 36.70% resistant and 63.60% susceptible. LVFX's MIC ranged from 0.25 to 64 mg/L. Compared with the standard-dose group, the model-guided group showed a significantly higher success rate (98.00% vs. 80.00%), a greater proportion of 7-day clinical cures (68.00% vs. 54.00%), a higher rate of achieving the CFP-SUL pharmacodynamic target (86.00% vs. 70.00%), and a higher rate of achieving targets for both drugs (74.00% vs. 61.00%, P<0.05). The incidence of treatment failures (8.00% vs. 19.00%) and adverse events (5.00% vs. 16.00%) was lower in the model-guided group (P<0.05). Compared with Child-Pugh Class B, Class C patients had a lower incidence of adverse reactions (3.75% vs. 15.00%, P<0.05) and a higher overall treatment success rate for pneumonia and urinary tract infections (92.50% vs. 82.50%, P<0.05).

Conclusion: Model-guided CFP-SUL with LVFX dose optimization in pneumonia with urinary tract infection and hepatic dysfunction improves patient acceptance of intention-to-treat and treatment outcomes.

Objectives: To investigate the therapeutic effects of Yangxin granules (YNX), a classic traditional Chinese medicine, in acute myocardial infarction (AMI) and its underlying mechanism. Methods: Rats were subjected to left anterior descending coronary artery ligation to establish AMI. Thereafter, YNX was administered once daily for 4 weeks. Cardiac function, histopathological changes, iron deposition, oxidative stress, and ferroptosis related proteins were evaluated. RNA sequencing was performed to identify differentially expressed genes and associated signaling pathways. H9c2 cells were treated with YNX in vitro under hypoxic conditions, followed by the supplementation of either a ferroptosis inducer or nuclear factor kappa B (NF-κB) activator. Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), iron, and ferroptosis and NF-κB pathway related proteins were measured. Results: YNX notably enhanced cardiac function, mitigated myocardial injury, alleviated fibrosis, and inhibited iron deposition and oxidative stress in AMI rats. Mechanistically, YNX suppressed ferroptosis by decreasing transferrin receptor 1 (TFR-1) and increasing anti-ferroptotic protein levels. Transcriptomic analysis and western blotting revealed that YNX inhibited NF-κB activity, which was derived from decreased phosphorylation of IκBα and NF-κB p65 inhibitor. In vitro assays revealed that 40 μg/mL YNX enhanced H9c2 cell proliferation, decreased LDH, ROS, and iron ion levels, downregulated ferroptosis-related proteins, and inhibited NF-κB pathway activation under hypoxic conditions. These effects were reversed when the cells were treated with a ferroptosis inducer or NF-κB pathway activator. Conclusions: YNX alleviates AMI by suppressing ferroptosis by inhibiting the NF-κB pathway, modulating iron metabolism, and mitigating oxidative stress.

Objective: This study aimed to develop and validate a predictive model for neonatal hypoglycemia (NH) risk in infants born to mothers with gestational diabetes mellitus (GDM).

Methods: A multicenter retrospective cohort study included 3215 GDM mother-infant pairs from five hospitals in Tianjin. Data were split into training, internal, and external validation sets. Risk factors were selected by expert consultation and univariate analysis. Logistic regression, random forest (RF), and radial basis function neural network models were built and evaluated using AUC, sensitivity, and specificity.

Results: Fourteen risk factors were identified, with hypothermia (OR = 2.31), insulin treatment during pregnancy (OR = 2.15), and large for gestational age (OR = 2.08) being the strongest. The RF model performed best, with AUC values of 0.896, 0.872, and 0.865 across validation groups. In external validation (threshold = 0.38), sensitivity was 82.19% and specificity 79.38%. Subgroup analysis by maternal age, gestational week, and neonatal sex showed stable performance (AUC 0.848-0.895). A simplified RF model using five key predictors retained 97.34% of performance (AUC = 0.842) and reduced assessment time to 2-3 minutes.

Conclusion: The RF model effectively predicts NH risk in GDM newborns with strong generalizability, supporting early clinical identification and intervention. Hypothermia, insulin use, and large for gestational age are core risk factors.

Objective: To evaluate the preventive effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on post-stroke cognitive impairment (PSCI) in patients with type 2 diabetes mellitus (T2DM) and concurrent acute ischemic stroke (AIS).

Methods: A retrospective cohort study was conducted on 236 patients with T2DM+AIS recruited from April 2021 to October 2024. Patients were grouped based on DPP-4i use: an observation group (107 cases) with DPP-4i therapy and a control group (129 cases) without. Patients' baseline demographics, clinical features, laboratory indices, and follow-up data were extracted from the electronic medical record system. The primary outcome measure was the incidence of PSCI, defined as a Montreal Cognitive Assessment Scale (MoCA) score <26 at six months after AIS. Secondary outcomes included inflammatory cytokines, oxidative stress markers, neuroprotective factors (BDNF), glycemic metabolism indicators, and life quality [Barthel Index (BI), Functional Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL)].

Results: At 6 months after AIS, the incidence of PSCI was significantly lower in the observation group than in the control group (P<0.05). Furthermore, inflammatory and oxidative stress marker levels were decreased whereas BDNF level was significantly elevated in the observation group compared to the control group (all P<0.05). According to the quality-of-life assessment, patients receiving DPP-4i had higher BI, FIM, and IADL scores (P<0.05), along with a lower all-cause readmission rate (P<0.05). Subgroup analysis indicated that different DPP-4i types (e.g., sitagliptin, saxagliptin) had consistent cognitive protective effects (P>0.05).

Conclusion: DPP-4i can lower PSCI risk in T2DM+AIS patients. Its mechanism involves multi-dimensional effects like anti-inflammation, anti-oxidation, insulin sensitivity enhancement, and neuroprotection.