The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX) biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-μ (PFTμ), sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2), p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFTμ, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.
Background: For patients with solitary huge (>10 cm in size) hepatocellular carcinoma (HCC) and without major vascular invasion, the treatment efficacy between surgical resection (SR) and transarterial chemoembolization (TACE) is not well studied. We aimed to compare the prognoses between SR and TACE for patients with solitary huge HCC. Methods:We enrolled 143 patients with treatment-naïve, solitary HCC (>10 cm) who had received either SR or TACE treatment between 2007-2016. Factors of overall survival (OS) were analyzed by multivariate analysis. Propensity scores matching (PSM) method was adopted to adjust baseline demographic differences for further analysis.Results: Ninety patients underwent SR and 53 patients received TACE. After a median follow-up of 17.0 (interquartile range 7.7-45.6) months, 83 patients had died. The cumulative 5-year OS rate was 44.7% and 11.7% for the SR group and the TACE group, respectively (P<0.001). A multivariate analysis showed that TACE [hazard ratio (HR): 3.515, 95% confidence interval (CI): 2.202-5.610, P<0.001], and albuminbilirubin (ALBI) grade >1 (HR: 2.181, 95% CI: 1.343-3.543, P=0.002) were the independent risk factors associated with poorer OS. After PSM, 37 pairs of matched patients were selected from each treatment arm. After matching, patients who underwent SR still evinced a significantly higher OS than did those who underwent TACE (P=0.010).Conclusions: SR provided a better OS than did TACE for patients with solitary huge (≥10 cm) HCC. As such, SR is recommended as the therapeutic priority for these patients.
We are reporting on an experimental investigation of a movable diffuse reflectance spectroscopy system to extract diagnostically relevant optical properties of two-layered tissue phantoms simulating mucosae that are covered with stratified squamous epithelium. The reflectance spectra were measured at multiple sourcedetector separations using two imaging fiber bundles in contact with the phantoms, one with its optical axis perpendicular to the sample surface (perpendicular probe) and the other with its distal end beveled and optical axis tilted at 45 deg (oblique probe). Polystyrene microspheres and purified human hemoglobin were used to make tissue phantoms whose scattering and absorption properties could be well controlled and theoretically predicted. Monte Carlo simulations were used to predict the reflectance spectra for system calibration and an iterative curve fitting that simultaneously extracted the top layer reduced scattering coefficient, thickness, bottom layer reduced scattering coefficient, and hemoglobin concentration of the phantoms. The errors of the recovered parameters ranged from 7% to 20%. The oblique probe showed higher accuracy in the extracted top layer reduced scattering coefficient and thickness than the perpendicular probe. The developed system and data analysis methods provide a feasible tool to quantify the optical properties in vivo.
Background: The incidence of hepatocellular carcinoma (HCC) is significantly higher in men than women. Nonetheless, the impact of sex disparities on HCC outcomes remains unclear. We aimed to compare the clinical manifestations and prognoses between male and female patients with HCC. Methods: This retrospective study enrolled 5337 consecutive patients (3976 men, 1361 women) who were diagnosed with HCC from 2007 to 2020. The prognostic factors were identified by the Cox proportional hazards model. Results: Male patients were younger upon HCC diagnosis (median age 64 vs 69 years; p < 0.001) with more favorable hepatic functional reserves (39.0% vs 35.1% albumin-bilirubin grade 1; p = 0.025) but had greater tumor burdens than the female patients. Furthermore, fewer male patients underwent curative therapies for HCC compared with the female patients (49.0% vs 57.0%; p < 0.001). After a median follow-up of 20.1 months (interquartile range, 5.8-47.3 months), 3133 patients died. The cumulative 5-year overall survival rates were 37.1% and 41.9% for male and female patients, respectively (p < 0.001). From the multivariate analysis, male sex was not an independent factor predictive of poor overall survival in all patients and in the subgroup analysis stratified by treatment modalities. When stratified by age, the female sex was an independent factor associated with lower mortality in younger (≤50 years) patients but not in older patients with HCC. Conclusion: Sex was not an independent predictor of the outcome of patients with HCC, especially for those aged more than 50 years.
Initial symptoms of paraquat (PQ) toxicity are often not obvious, and the lack of advanced testing equipment and medical conditions in the primary hospital make it difficult to provide early diagnosis and timely treatment. To explore simple, objective, and effective indicators of prognosis for primary clinicians, we retrospectively analyzed acute PQ poisoning in 190 patients admitted to our hospital from 2008 to 2017. Based on their condition at the time of discharge, patients were categorized into either the survival group ( n = 71) or the mortality group ( n = 119). Age, PQ ingested amount, urinary PQ, urinary protein, white blood cell (WBC), and serum creatinine (Cr) were the key factors associated with the prognosis for PQ poisoning. We identified specific diagnostic thresholds for these key indicators of PQ poisoning: PQ ingested amount (36.50 mL), urinary PQ (semiquantitative result “++”), urinary protein (semiquantitative result “±”), WBC (16.50 × 109/L), and serum Cr (102.10 µmol/L). Combining these five indicators to identify poisoning outcomes was considered objective, accurate, and convenient. When the combined score was <1, the predicted probability of patient death was 6%. When the combined score was ≥3, the predicted probability of patient death was 96%. These findings provide metrics to assist primary clinicians in predicting outcomes of acute PQ poisoning at earlier stages, a basis for administering treatment.
Two Ty1/copia-like retrotransposons, RTvr1 and RTvr2, were isolated from mung bean (Vigna radiata (L.) Wilczek) genomic DNA and are the first complete elements of this kind to be reported in this legume. Nucleotide sequence analyses revealed that both elements are AT-rich (60% and 61%, respectively) and are flanked by a target-site duplication of 5 bp. The structures of RTvr1 and RTvr2 are those of typical long terminal repeat retrotransposons. Both transposons were able to produce putative proteins with the domain order of Gag-protease-integrase-reverse transcriptase-RNase H, indicating that RTvr1 and RTvr2 belong to the Ty1/copia-like retrotransposons. Except for a 2,500-bp insertion region in RTvr2, the overall similarity between RTvr1 and RTvr2 is 92%. Dot blots showed that these two retroelements were present at a copy number of 120 per mung bean haploid genome. Multiple sequence alignments showed that the conserved motifs of the aspartic proteases, integrase, reverse transcriptase, and the RNase H in the Ty1/copia-like group all exist in RTvr1 and RTvr2.
Objective: To investigate the outcomes of open reduction and internal fixation combined with medial buttress plate (MBP) and allograft bone-assisted cannulated screw (CS) fixation for patients with unstable femoral neck fracture with comminuted posteromedial cortex. Methods:In a retrospective study of patients operated on for unstable femoral neck fractures with comminuted posteromedial cortex from March 2016 to August 2020, the clinical and radiographic outcomes of 48 patients treated with CS + MBP were compared with the outcomes of 54 patients treated with CS only. All patients in the CS + MBP group were fixed by three CS and MBP (one-third tubular plates or reconstructive plates) with bone allografts. The surgeryrelated outcomes and complications were evaluated, including operative time, blood loss, union time, femoral head necrosis, femoral neck shortening, and other complications after the operation. The Harris score was evaluated at 12 months after the operation.Results: All patients were followed up for 12-40 months. The average age of patients in the CS-only group (54 cases, 22 females) and CS + MBP group (48 cases, 20 females) was 48.46 AE 7.26 and 48.73 AE 6.38 years, respectively. More intraoperative blood loss was observed in the CS + MBP group than that of patients in CS-only group (153.45 AE 64.27 vs 21.86 AE 18.19 ml, t = 4.058, P = 0.015). The average operative time for patients in the CS + MBP group (75.35 AE 27.67 min) was almost double than that of patients in the CS-only group (36.87 AE 15.39 min) (t = 2.455, P < 0.001). The Garden alignment index of patients treated by CS + MBP from type I to type IV was 79%, 19%, 2%, and 0%, respectively. On the contrary, they were 31%, 43%, 24% and 2% for those in the CS-only group, respectively. The average healing times for the CS-only and CS + MBP groups were 4.34 AE 1.46 and 3.65 AE 1.85 months (t = 1.650, P = 0.102), respectively. Femoral neck shortening was better in the CS + MBP group (1.40 AE 1.73 mm, 9/19) than that in the CS-only group (4.33 AE 3.32 mm, 24/44). Significantly higher hip function was found in the CS + MBP group (85.60 AE 4.36 vs 82.47 AE 6.33, t = 1.899, P = 0.06). There was no statistical difference between femoral head necrosis (4% vs 11%, χ 2 = 1.695, P = 0.193) and nonunion (6% vs 9%, χ 2 = 0.318, P = 0.719). Conclusion:For unstable femoral neck fractures with comminuted posteromedial cortex, additional MBP combined with bone allografts showed better reduction quality and neck length control than CS fixation only, with longer operative time and more blood loss.
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