Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

N-Acetyl Serotonin Provides Neuroprotective Effects by Inhibiting Ferroptosis in the Neonatal Rat Hippocampus Following Hypoxic Brain Injury.

Hypoxic-ischemic encephalopathy is the main cause of infant brain damage, perinatal death, and chronic neonatal disability worldwide. Ferroptosis is a new form of cell death that is closely related to hypoxia-induced brain damage. N-Acetyl serotonin (NAS) exerts neuroprotective effects, but its effects and underlying mechanisms in hypoxia-induced brain damage remain unclear. In the present study, 5-day-old neonatal Sprague-Dawley rats were exposed to hypoxia for 7 days to establish a hypoxia model. Histochemical staining was used to measure the effects of hypoxia on the rat hippocampus. The hippocampal tissue in the hypoxia group showed significant atrophy. Hypoxia significantly increased the levels of prostaglandin-endoperoxide synthase 2 (PTGS2) and the iron metabolism-related protein transferrin receptor 1 (TfR1) and decreased the levels of glutathione peroxidase 4 (GPX4). These changes resulted in mitochondrial damage, causing neuronal ferroptosis in the hippocampus. More importantly, NAS may improve mitochondrial function and alleviate downstream ferroptosis and damage to the hippocampus following hypoxia. In conclusion, we found that NAS could suppress neuronal ferroptosis in the hippocampus following hypoxic brain injury. These discoveries highlight the potential use of NAS as a treatment for neuronal damage through the suppression of ferroptosis, suggesting new treatment strategies for hypoxia-induced brain damage.

Cluster validity indices for mixture hazards regression models.

In the analysis of survival data, the problems of competing risks arise frequently in medical applications where individuals fail from multiple causes. Semiparametric mixture regression models have become a prominent approach in competing risks analysis due to their flexibility and easy interpretation of resultant estimates. The literature presents several semiparametric methods on the estimations for mixture Cox proportional hazards models, but fewer works appear on the determination of the number of model components and the estimation of baseline hazard functions using kernel approaches. These two issues are important because both incorrect number of components and inappropriate baseline functions can lead to insufficient estimates of mixture Cox hazard models. This research thus proposes four validity indices to select the optimal number of model components based on the posterior probabilities and residuals resulting from the application of an EM-based algorithm on a mixture Cox regression model. We also introduce a kernel approach to produce a smooth estimate of the baseline hazard function in a mixture model. The effectiveness and the preference of the proposed cluster indices are demonstrated through a simulation study. An analysis on a prostate cancer dataset illustrates the practical use of the proposed method.

RANKL and OPG Polymorphisms Are Associated with Aromatase Inhibitor-Related Musculoskeletal Adverse Events in Chinese Han Breast Cancer Patients.

BACKGROUND: Breast cancer patients treated with aromatase inhibitors (AIs) may experience musculoskeletal adverse events (MS-AEs). Several studies have confirmed that the RANKL/RANK/OPG signaling pathway plays a dominant role in bone health. Therefore, this study aimed to analyze the relationship between the serum levels of RANKL, OPG and their SNPs (single nucleotide polymorphisms) with AI-related MS-AEs. METHODOLOGY AND PRINCIPAL FINDINGS: Patients with early stage, hormone-sensitive breast cancer who were receiving AI therapy were enrolled. We included 208 cases with AI-related MS-AEs and 212 without (controls). The levels of estradiol, bone-turnover markers, multiple inflammatory cytokines, RANKL,OPG and lumbar spine BMD were measured, and questionnaires were completed. We analyzed 29 SNPs of RANKL, RANK and OPG using Sequenom MassARRAY assays and PCR-based TaqMan assays. The levels of bone-turnover markers and RANKL and the ratio of RANKL/OPG were higher in patients with AI-related MS-AEs than controls (all p < 0.05). A genetic assay showed that the RANKL SNP rs7984870 and OPG SNP rs2073618 were associated with AI-related MS-AEs. In patients with AI-related MS-AEs, rs7984870 CC and rs2073618 CC were risk genotypes. Carriers of the rs7984870 CC genotype were more likely to have a higher RANKL level and RANKL/OPG ratio than carriers of the GG genotype, and carriers of the rs2073618 CC genotype were more likely to have a lower OPG level and a higher RANKL/OPG ratio than carriers of the GG genotype (all p < 0.05). Moreover, risk genotypes were associated with higher levels of serum CTX and PINP and a lower lumbar spine BMD (all p < 0.05). CONCLUSIONS AND SIGNIFICANCE: In conclusion, the RANKL and OPG risk genotypes synergize to negatively impact bone health and predispose breast cancer patients to AI-related MS-AEs.

miRNA-24-3p promotes cell proliferation and inhibits apoptosis in human breast cancer by targeting p27Kip1.

MicroRNAs (miRNAs) are often aberrantly expressed in breast cancer and are postulated to play a role in its initiation and progression. In the present study, we found that the expression level of miR-24-3p was upregulated in breast cancer in comparison with the level in adjacent normal tissues. Overexpression of miR-24-3p was able to promote cell proliferation and inhibit cell apoptosis in MDA-MB-435 and MDA-MB-468 cells. With the bioinformatic method, we further identified that p27Kip1 is a direct target of miR-24-3p, and its protein level was negatively regulated by miR-24-3p. Therefore, the data reported here demonstrate that miR-24-3p is an important regulator in breast cancer, and imply that the miR-24-3p/p27Kip1 axis has potential as a therapeutic target for breast cancer.

Indications of clinical and genetic predictors for aromatase inhibitors related musculoskeletal adverse events in Chinese Han women with breast cancer.

BACKGROUND: Women with breast cancer treated with aromatase inhibitors (AIs) may experience musculoskeletal symptoms that lead to discontinuation of effective therapy. The purpose of the current study is to evaluate the clinical and genetic predictors for AIs-related musculoskeletal adverse events(MS-AEs). METHODOLOGY AND PRINCIPAL FINDINGS: We recruited 436 postmenopausal Chinese Han women receiving adjuvant AIs therapy for early-stage hormone-sensitive breast cancer. Patients completed a self-administered questionnaire assessing the presence of musculoskeletal symptoms that started or worsened after initiating AIs. 27 single nucleotide polymorphisms (SNP) of ESR1, ESR2 and PGR were analyzed by Sequenom MassARRAY assays and /or PCR-based TaqMan assays.Of the 436 enrolled women, 206 cases experienced musculoskeletal symptoms.Patients who received taxane chemotherapy were more than two times more likely than other patients to have AIs-related MS-AEs. Genetic assay had showed that only two ESR1 SNPs, rs2234693 and rs9340799 were associated with AIs-related MS-AEs.TT genotype and the T allele in rs2234693 was statistically significantly lower in AIs-Related MS-AEs group than controls (P = 0.001; P = 9.49E-7). The frequency of AA genotype and the A allele in rs9340799 was higher (P = 2.20E-5; P = 3.09E-4). CONCLUSIONS AND SIGNIFICANCE: Our results suggested that prior taxane-based chemotherapy was the clinical predictor, while rs2234693 and rs9340799 were the genetic predictors for AIs-related MS-AEs.

Extraction optimization of Bruguiera gymnorrhiza polysaccharides with radical scavenging activities.

Box-Behnken design including independent variables such as extraction temperature (60-80°C), extraction time (20-40 min) and ratio of water to raw material (30-50 mL/g) was used to optimize the extraction process of Bruguiera gymnorrhiza polysaccharides (BGPs). The experimental data were fitted to a second-order polynomial equation using multiple regression analysis. The optimum conditions were predicted as follows: extraction temperature 71°C, extracting time 31.4 min, and ratio of water to raw material 42. Under these conditions, the yield of BGPs obtained was (16.43 ± 0.08)%, which was in good agreement with the predicted value 16.47%. Additionally, characterization of BGPs was obtained by FT-IR analysis. The antioxidant activities of BGPs were evaluated in vitro. BGPs demonstrated appreciable antioxidant potential on superoxide anion radical, ABTS radical, and hydroxyl radical scavenging. These may provide theoretical basis for further system research and rational development and utilization of mangrove resources.

The expression and clinical significance of microRNA-1258 and heparanase in human breast cancer.

OBJECTIVES: To investigate the expression profile of miR-1258 and heparanase (HPSE) in breast cancer and to assess their clinicopathological significance. DESIGN AND METHODS: The expression levels of miR-1258 and HPSE were analyzed in normal, benign and malignant breast tissues. Their serum levels were evaluated in healthy women and in patients with benign and malignant breast disease. We studied the correlation between the expression of miR-1258 and HPSE and the clinical features presented by the patients. RESULTS: MiR-1258 was down-regulated and HPSE was up-regulated in breast cancer, with a significant inverse correlation. A reduced miR-1258 expression and an elevated HPSE expression were associated with the lymph node status, late clinical stages, a short overall survival and a short relapse-free survival. In frozen fresh tissue samples, the miR-1258 levels in breast cancer with lymph node metastasis were significantly lower than that of breast cancer without lymph node metastasis and benign disease (BD). In contrast, the HPSE levels in breast cancer with lymph node metastasis were the highest. In serum samples, the miR-1258 levels in metastatic breast cancer (M1) were lower than that of primary breast cancer (M0) and BD. However, serum HPSE levels of M1 patients were significantly higher than that of M0 patients and BD patients. CONCLUSIONS: MiR-1258 may play an important role in breast cancer development and progression by regulating the expression of HPSE, and they might be potential prognostic biomarkers for breast cancer.

Risk factors of urinary frequency among women aged 60 and older in Taiwan.

OBJECTIVE: To assess the associated risk factors for daytime urinary frequency among Taiwanese women aged = 60 years. MATERIALS AND METHODS: Daytime urinary frequency, defined by the International Continence Society, and its associated problems were evaluated, and medical history and sociodemographic variables were recorded. A total of 2,410 women were selected by a multistage random sampling method. The factors were assessed by frequency and Pearson's ?2 test using a significance level of < 0.05. RESULTS: A total of 621 women of those initially selected in the study died before completion of this study. Face-to-face interviews with 1,521 women were completed, producing a response rate of 85.0% (1,521/1,789 women). The prevalence of daytime urinary frequency was significantly related to body mass index (p = 0.018), diabetes mellitus (p = 0.017), hypertension (p = 0.015), previous drug allergy (p = 0.003), smoking (p = 0.005), hormone therapy (p = 0.019), parity (p = 0.019), and urinary incontinence (p = 0.000). However, there was no association between urinary frequency and previous gynecologic surgery, hysterectomy, alcohol consumption, marital status, childbirth, and age of menopause. CONCLUSION: The results of this study showed a relatively high risk of urinary frequency development in patients with urinary incontinence, diabetes mellitus, hypertension, obesity, and smoking that are preventable, modifiable, or controllable. Better quality of health education for these women, drawing their attention to the associated factors, may have an impact on the prevalence of urinary frequency.

Prevalence of urinary frequency among women aged 60 years and older in Taiwan.

OBJECTIVE: To evaluate the prevalence of daytime urinary frequency among Taiwanese women aged 60 years and older. MATERIALS AND METHODS: There were an estimated 1.25 million female residents aged 60 years and over in Taiwan in 2000. A sample of 2,410 women was selected using a multistage random sampling method. Face-to-face visits with 1,523 women were completed by trained professional interviewers within 3 months of the subjects selection. Questions about urinary frequency and other lower urinary tract symptoms, sociodemographics, reproduction, and medical and surgical histories were recorded. The factors were assessed by frequency and Pearson's Chi-squared test using a significance level of < 0.05. RESULTS: The prevalence of urinary frequency in Taiwanese women aged 60 years and over was 18.8% (286/1,521). The response rate was 85.0% (1,521/1,789). For those who complained of frequency, 45.8% voided 8-15 times a day, 37.8% voided 16-23 times a day, 1.7% voided 24-31 times and a day, and 14.7% voided more than 31 times a day. The prevalence of urinary frequency was significantly associated with age (p < 0.001). CONCLUSION: Urinary frequency is a common symptom in menopausal women and is significantly related to age. More than half of the women interviewed experienced intervals of < 1 hour between visits to the restroom during the day.