Association of healthy diet score and adiposity with risk of colorectal cancer: findings from the UK Biobank prospective cohort study.

PURPOSE: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. METHODS: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. RESULTS: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. CONCLUSION: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk.

Association between smoking, smoking cessation and serum α-klotho levels among American adults: National Health and Nutrition Examination Survey.

α-klotho is an anti-aging protein. The correlation between smoking, smoking cessation and serum α-klotho levels remains controversial. The aim of this study was to investigate the association between smoking, smoking cessation and serum α-klotho levels. This cross-sectional study finally included 4877 participants, aged 40-79 years, who participated in the National Health and Nutrition Examination Survey studies from 2013 to 2016. Of these, 2312 (47.4%) were men and 894 (18.3%) were current smokers, and the mean age of the participants was 57.8±10.7 years. Multivariate linear regression modeling was used to assess the association between smoking, smoking cessation and serum α-klotho levels. After adjustment for multiple confounders, this study observed that smoking was negatively associated with serum α-klotho levels (ß: -58.3; 95% confidence interval CI: -82.0 to -34.6; p<0.001), whereas smoking cessation was positively associated with serum α-klotho levels (ß: 52.3; 95% CI: 24.1 to 80.6; p<0.001). In subgroup and interaction analyses, p-value for the interaction between smoking and race on serum klotho levels was found to be less than 0.001. The correlation between smoking, smoking cessation and serum α-klotho levels remained stable after propensity score matching (ß: -54.1; 95% CI: -81.5 to -26.7; p<0.001, ß: 54.8; 95% CI: 24.2 to 85.4; p<0.001). In a large sample population, the present study found that smoking, smoking cessation and serum α-klotho levels were associated in opposite directions.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Objective: Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Methods: Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. Results: In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Conclusion: Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Secular trend in disease burden of leukemia and its subtypes in China from 1990 to 2019 and its projection in 25 years.

Leukemia and its subtypes impose a major public health challenge in China. Identifying the secular trend of leukemia burden is critical to facilitate optimal healthcare planning and improve the management of leukemia. The incidence rates of leukemia from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database according to the following: subtype (acute lymphocytic leukemia [ALL], acute myeloid leukemia [AML], chronic lymphocytic leukemia [CLL], chronic myelogenous leukemia [CML], and other leukemia subtypes), sex, and age group. The average annual percentage changes and relative risks were calculated using joinpoint regression and the age-period-cohort model, respectively. The Bayesian age-period-cohort model was also applied to predict the future trend of the incidence of leukemia and its subtypes in the next 25 years. From 1990 to 2019, the age-standardized incidence rates (ASIRs) of leukemia slightly declined in males and females, which is similar to the trend of other leukemia subtypes. However, the four major leukemia subtypes, namely, ALL, AML, CLL, and CML, have been on the rise over the past three decades. The incidence rates of leukemia in children and the elderly were considerably higher than those in other age groups in males and females. Age effects were the most influential risk factor for leukemia incidence. Period effects showed that the risks of leukemia and its subtypes incidence increased with time. For cohort effects, the risks of leukemia and its subtypes were higher among the early-born cohorts compared with the late-born cohorts. The ASIRs of leukemia and its subtypes will continue to increase in the next 25 years. The burden of leukemia and its subtypes is expected to continue to increase in the next 25 years in males and females. A comprehensive understanding of the risk characteristics and disease pattern of leukemia and its subtypes is needed to formulate timely and effective intervention measures to reduce the leukemia burden in China.

Trend and projection of larynx cancer incidence and mortality in China from 1990 to 2044: A Bayesian age-period-cohort modeling study.

BACKGROUND: Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear. METHODS: The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age-period-cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044. RESULTS: From 1990 to 2019, the age-standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI -0.1 to 0) in females. The age-standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI -1.1 to -0.6) and 2.2% (95% CI -2.8 to -1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age-standardized incidence rates of larynx cancer continued to increase in males, whereas the age-standardized mortality rates continued to decrease in both males and females. CONCLUSION: The burden of larynx cancer in China has a significant gender difference. The age-standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively.

Stigma receptors control intraspecies and interspecies barriers in Brassicaceae.

Flowering plants have evolved numerous intraspecific and interspecific prezygotic reproductive barriers to prevent production of unfavourable offspring1. Within a species, self-incompatibility (SI) is a widely utilized mechanism that rejects self-pollen2,3 to avoid inbreeding depression. Interspecific barriers restrain breeding between species and often follow the SI × self-compatible (SC) rule, that is, interspecific pollen is unilaterally incompatible (UI) on SI pistils but unilaterally compatible (UC) on SC pistils1,4-6. The molecular mechanisms underlying SI, UI, SC and UC and their interconnections in the Brassicaceae remain unclear. Here we demonstrate that the SI pollen determinant S-locus cysteine-rich protein/S-locus protein 11 (SCR/SP11)2,3 or a signal from UI pollen binds to the SI female determinant S-locus receptor kinase (SRK)2,3, recruits FERONIA (FER)7-9 and activates FER-mediated reactive oxygen species production in SI stigmas10,11 to reject incompatible pollen. For compatible responses, diverged pollen coat protein B-class12-14 from SC and UC pollen differentially trigger nitric oxide, nitrosate FER to suppress reactive oxygen species in SC stigmas to facilitate pollen growth in an intraspecies-preferential manner, maintaining species integrity. Our results show that SRK and FER integrate mechanisms underlying intraspecific and interspecific barriers and offer paths to achieve distant breeding in Brassicaceae crops.

Vaginal microbiota and personal risk factors associated with HPV status conversion-A new approach to reduce the risk of cervical cancer?

Vaginal microbiota (VMB) is associated with changes in Human papilloma virus (HPV) status, which consequently influences the risk of cervical cancer. This association was often confounded by personal risk factors. This pilot research aimed to explore the relationship between vaginal microbiota, personal risk factors and their interactions with HPV status conversion to identify the vaginal microbiota that was associated with HPV clearance under heterogeneous personal risk factors. A total of 38 women participated by self-collecting a cervicovaginal mucus (CVM) sample that was sent for metagenomics sequencing. Most of the participants also filled in personal risk factors questionnaire through an eHealth platform and authorized the use of their previous HPV genotyping results stored in this eHealth platform. Based on the two HPV results, the participants were grouped into three cohorts, namely HPV negative, HPV persistent infection, and HPV status conversion. The relative abundance of VMB and personal factors were compared among these three cohorts. A correlation investigation was performed between VMB and the significant personal factors to characterize a robustness of the panel for HPV status change using R programming. At baseline, 12 participants were HPV-negative, and 22 were HPV-positive. Within one year, 18 women remained HPV-positive, 12 were HPV-negative and 4 participants showed HPV clearance. The factors in the eHealth questionnaire were systematically evaluated which identified several factors significantly associated with persistent HPV infection, including age, salary, history of reproductive tract infection, and the total number of sexual partners. Concurrent vaginal microbiome samples suggest that a candidate biomarker panel consisting of Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella bacteria, which may be associated with HPV clearance. This pilot study indicates a stable HPV status-related vaginal microbe environment. To establish a robust biomarker panel for clinical use, larger cohorts will be recruited into follow-up studies.

Secular Trends in the Burden of Multiple Myeloma From 1990 to 2019 and Its Projection Until 2044 in China.

Objective: Multiple myeloma (MM) imposes a heavy burden in China. Understanding the secular trend of MM burden and projecting its future trend could facilitate appropriate public health planning and improve the management of MM. Methods: Sex-specific incidence and mortality rates of MM in China from 1990 to 2019 were collected from the Global Burden of Disease 2019 study. The secular trend of MM burden was analyzed by joinpoint regression. Age-period-cohort model was used to analyze the effects of age, period, and birth cohort on MM burden and project future trends up to 2044. Results: From 1990 to 2019, the age-standardized incidence and mortality rates of MM continued to increase in males. For females, the age-standardized rates were stable in MM incidence and decreased in MM mortality. Males had a higher disease burden of MM than females. Age effects were the most significant risk factor for MM incidence and mortality. Moreover, the risk of MM incidence and mortality increased with increasing time period but decreased with birth cohort in males and females. The age-standardized incidence and mortality rates of MM in China is predicted to be continuously increasing over the next 25 years. Conclusion: The burden of MM in China is expected to continue to increase in the future, with significant sex difference. A comprehensive understanding of the risk characteristics and disease pattern of MM could help develop timely intervention measures to effectively reduce its burden.

Prognostic value of PD-L1 and Siglec-15 expression in patients with nasopharyngeal carcinoma.

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in nasopharyngeal carcinoma (NPC) patients. We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescence staining in 182 NPC tissue samples. A significant correlation was identified between the PD-L1 and Siglec-15 expression (P = 0.000). Moreover, Kaplan-Meier survival curves showed that PD-L1 expression was associated with improved overall survival (OS) (P = 0.025) and Siglec-15 expression was associated with improved distant failure-free survival (D-FFS) (P = 0.048). Moreover, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of OS (P = 0.020) and D-FFS (P = 0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression had significant advantages regarding OS, compared to other groups (P = 0.037). PD-L1 and Siglec-15 may represent novel biomarkers for predicting the prognosis of NPC patients. Siglec-15 may be considered as a potential target for the development of therapeutics for NPC treatment in the future.

Understanding the experiences of older caregivers of patients with lung cancer during palliative chemotherapy in China: a qualitative study.

PURPOSE: Although there has been an increase in research on caregivers of patients with cancer, there has been little focus on the specific experiences of older caregivers of patients with lung cancer and the effect of their cultural backgrounds on their experiences. This study explored the caregiver experience among the ageing population in China. METHODS: Older caregivers of patients with lung cancer undergoing palliative chemotherapy were recruited. Data were collected using a qualitative descriptive design involving semi-structured interviews, which were recorded, transcribed verbatim and analysed qualitatively using inductive content analysis. RESULTS: Eighteen caregivers aged 61-81 years completed the interviews. The following four themes were identified: physical difficulty, living with ambivalence, perception of role and role-related behaviour changes. These themes enabled a greater understanding of role-related behaviours in older caregivers and their challenges in addressing biological and psychosocial challenges related to older age. CONCLUSION: The present study highlighted the vulnerability and perceived challenges of the role of older caregivers. These findings help lay the foundation for interventions to improve the care provided to caregivers and their health outcomes, especially caregivers with chronic conditions.

Preoperative C-reactive protein to prealbumin ratio is independently associated with prognosis in patients with resectable colorectal cancer.

BACKGROUND: Increasing attention has been drawn the prognostic value of inflammatory indices for colorectal cancer (CRC). However, the prognostic value of the preoperative C-reactive protein to prealbumin ratio (CPAR) in CRC remains unclear. METHODS: A retrospective study was conducted with 794 patients who had CRC and underwent radical surgical resection. The predictive performance of the inflammatory indices was analyzed and compared using the area under the time-dependent receiver operating characteristic curve. A competing risk regression model and Cox proportional hazard model were used to analyze the effects of CPAR on disease-free survival (DFS) and overall survival (OS), respectively. RESULTS: Patients with high CPAR (>7.25) had poor survival outcome. The CPAR had the best predictive performance among all inflammatory indices, and was significantly associated with several characteristics of tumor invasion, including histological grade, tumor stage, and tumor size. Multivariate analysis showed that high CPAR was independently associated with poor DFS (subdistribution hazard ratio = 2.28, 95% confidence interval [CI]: 1.74-2.82) and OS (hazard ratio = 1.78, 95% CI: 1.60-1.96). CONCLUSION: Preoperative CPAR assessment could serve as an effective and reliable tool for prognostic prediction in patients with resectable CRC.

A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo.

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.

HeLa Cell-Derived Paclitaxel-Loaded Microparticles Efficiently Inhibit the Growth of Cervical Carcinoma.

AIM: Tumor cell-derived microparticles (MP) can function as a targeted delivery carrier for anti-tumor drugs. Here, we aimed to generate paclitaxel-loaded microparticles (MP-PTX) from HeLa cells and examined its therapeutic potential on human cervical carcinoma. METHODS: MP-PTX was generated from HeLa cells by ultraviolet radiation and subsequent centrifugation. The particle size, drug loading rate, and stability of MP-PTX were examined in vitro. Flow cytometry and the MTT assay were performed to test the inhibitory effect of MP-PTX using different cell lines. Immunodeficient mice bearing HeLa cervical carcinoma were treated with 0.9% normal saline, MP, paclitaxel (PTX) (2.5 mg/kg), or MP-PTX (PTX content identical to PTX group) every day for 6 consecutive days. Tumor volume and animal survival were observed. Micro 18F-FDG PET/CT was performed to monitor the therapeutic efficacy. The proliferation activity of cells and microvessel density in tumor tissues were determined by immunohistochemical staining using Ki-67 and CD31, respectively. RESULTS: Dynamic laser scattering measurements showed that the particle size of MP-PTX was 285.58 ± 2.95 nm and the polydispersity index was 0.104 ± 0.106. And the particle size of MP-PTX was not change at 4°C for at least one week. More than 1% of PTX in the medium could be successfully encapsulated into HeLa cell-derived MP. When compared with PTX, MP-PTX treatment significantly increased apoptosis of tumor cells and reduced their proliferation. In addition, MP-PTX showed lower toxicity to normal human umbilical vein endothelial cells (HUVEC) than PTX. In vivo studies further demonstrated that MP-PTX treatment significantly inhibited the growth of cervical carcinoma, prolonged the survival of tumor-bearing mice, and reduced the toxicity of PTX. Immunohistochemical staining revealed that MP-PTX treatment led to decreased Ki-67 positive tumor cells and decreased microvessel density in tumor tissues. CONCLUSION: Our results demonstrated that HeLa-derived MP-PTX significantly enhanced the anti-cancer effects of PTX with reduced toxicity, which may provide a novel strategy for the treatment of cervical carcinoma.

Early Death Incidence and Prediction in Stage IV Breast Cancer.

BACKGROUND The early death of patients is a global cancer issue. We aimed to identify the risk factors for early death in stage IV breast cancer. Predictive nomograms for early death evaluation were generated based on the risk factors. MATERIAL AND METHODS Based on the Surveillance, Epidemiology, and End Results (SEER) database, patients diagnosed with IV breast cancer were selected. The risk factors for early death (survival time ≤1 year) were identified using logistic regression model analysis. Predictive nomograms were constructed and internal validation was performed. RESULTS A total of 5998 (32.6%) breast cancer patients were diagnosed as early death in the construction cohort. Age older than 50 years, unmarried status, black race, uninsured status, triple-negative type, grade (II and III), tumor size >5 cm, and metastasis to lung, liver, and brain were risk factors for total early death, while Luminal B subtype, N1 stage, and surgical interventions were associated with lower risk of early death. As for cancer-specific and non-cancer-specific early death, several factors were not consistent between the 2 groups. Nomograms for all-cause, cancer-specific, and non-cancer-specific early death were constructed. The calibration curve showed satisfactory agreement. The areas under the ROC curve (AUC) were 78.3% (95% CI: 77.7-78.9%), 75.8% (75.1-76.4%), and 72.3% (71.6-72.9%), respectively. In the validation cohort, a total of 689 (19.3%) patients were diagnosed as early death and the calibration curve showed satisfactory agreement. The AUCs of the all-cause, cancer-specific, and non-cancer-specific early death prediction were 74.0% (95% CI: 72.5-75.4%), 73.5% (72.0-74.9%), and 68.6% (67.0-70.1%), respectively. CONCLUSIONS Nomograms were generated to predict early death, with good calibration and discrimination. The predictive model can provide a reference for identifying cases with high risk of early death among stage IV breast cancer patients and play an auxiliary role in guiding individual treatment.

Management of Chemotherapy for Stage II Nasopharyngeal Carcinoma in the Intensity-Modulated Radiotherapy Era: A Review.

Nasopharyngeal carcinoma is an endemic disease with a high prevalence in Southeast Asia, Mediterranean countries, and Northern Africa. With substantial advances in screening and diagnosis, increasingly more early-stage (stage I~II) patients are being diagnosed. The undebated treatment modality for stage I patients is radiotherapy alone. However, controversies exist for patients with stage II disease, mostly revolving around the management of chemotherapy. However, the use of intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma has increased recently, which has drastically improved survival outcomes. Thus, many oncologists have considered omitting chemotherapy for stage II patients in the intensity-modulated radiotherapy era. Unfortunately, prospective studies comparing concurrent radio-chemotherapy with intensity-modulated radiotherapy alone are limited. Notably, stage II nasopharyngeal carcinoma consists of three subgroups, among which stage T2N1M0 disease is unique and potentially warrants additional treatment including chemotherapy. Additionally, molecular biology techniques are advancing at an incredible speed. Instead of adopting a one-size-fits-all recommendation, exploring potential predictive biomarkers to select patients who are likely to derive benefit from chemotherapy is a better choice. In this review, we summarize the data from studies and reviews regarding chemotherapy for stage II nasopharyngeal carcinoma in the intensity-modulated radiotherapy era and discuss chemotherapy utility. Eventually, we conclude that IMRT alone may be sufficient for stage II nasopharyngeal carcinoma, but this needs to be verified by prospective studies in the near future, the evidence collected thus far suggests that concurrent chemo-radiotherapy without induction or adjuvant chemotherapy is yet to be necessary for patients with stage II disease.

[Effect of auricular-point pressure combined with personalized music therapy on perioperative stress response in primipara].

OBJECTIVE: To explore the effect of auricula-point pressure combined with personalized music therapy on perioperative stress response in primipara. METHODS: A total of 1000 primiparas who were elective for cesarean section were randomly divided into an observation group and a control group, 500 cases in each one. 1 h before surgery and 3 h, 6 h, 12 h and 24 h after surgery, individualized music relaxation intervention was given for 1 h in the two groups. On the basis of the treatment, auricular-point pressure was added at Pizhixia (AT4), Shenmen (TF4), Xin (CO15), Zigong (uterus), Luanchao (ovary), Neishengzhiqi (TF2) in the observation group. Each point was pressed for 1 min each time, repeated once every 15 min, the force is from light to heavy, and it is better to have a feeling of distension, sourness and radiation in the auricle. The scores of anxiety self-rating scale, visual analog scale (VAS), heart rate, systolic blood pressure, thyroid stimulating hormone, cortisol and blood glucose levels were observed in the two groups. RESULTS: A total of 973 primiparas completed the clinical study in the end, including 488 patients in the observation group and 485 patients in the control group. Compared to enrollment, the scores of anxiety self-rating scale before entering the operating room in the two groups were significantly improved (P<0.05), and the observation group was superior to the control group (P<0.05). Entering the operating room and tracheal extubation, the heart rate and systolic blood pressure of the primiparas in the observation group were more stable than those in the control group, and the differences were statistically significant (P<0.05). Entering the operating room, 1 h into the surgery and 3 h after surgery, the thyroid stimulating hormone, cortisol and blood glucose levels of the primiparas in the observation group were significantly better than those in the control group (P<0.05). The VAS scores in the observation group at 6 h, 12 h and 24 h after surgery were lower than those in the control group (P<0.05). CONCLUSION: Auricular-point pressure combined with personalized music therapy can reduce the perioperative stress response in primipara and promote the improvement of psychological, physiological and emotional.

Breast Cancer Molecular Subtype Prediction by Mammographic Radiomic Features.

RATIONALE AND OBJECTIVES: This study aimed to investigate whether quantitative radiomic features extracted from digital mammogram images are associated with molecular subtypes of breast cancer. MATERIALS AND METHODS: In this institutional review board-approved retrospective study, we collected 331 Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 29 triple-negative, 45 human epidermal growth factor receptor 2 (HER2)-enriched, 36 luminal A, and 221 luminal B lesions. A set of 39 quantitative radiomic features, including morphologic, grayscale statistic, and texture features, were extracted from the segmented lesion area. Three binary classifications of the subtypes were performed: triple-negative vs non-triple-negative, HER2-enriched vs non-HER2-enriched, and luminal (A + B) vs nonluminal. The Naive Bayes machine learning scheme was employed for the classification, and the least absolute shrink age and selection operator method was used to select the most predictive features for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve and accuracy. RESULTS: The model that used the combination of both the craniocaudal and the mediolateral oblique view images achieved the overall best performance than using either of the two views alone, yielding an area under receiver operating characteristic curve (or accuracy) of 0.865 (0.796) for triple-negative vs non-triple-negative, 0.784 (0.748) for HER2-enriched vs non-HER2-enriched, and 0.752 (0.788) for luminal vs nonluminal subtypes. Twelve most predictive features were selected by the least absolute shrink age and selection operator method and four of them (ie, roundness, concavity, gray mean, and correlation) showed a statistical significance (P< .05) in the subtype classification. CONCLUSIONS: Our study showed that quantitative radiomic imaging features of breast tumor extracted from digital mammograms are associated with breast cancer subtypes. Future larger studies are needed to further evaluate the findings.

UNBS5162 inhibits proliferation of human melanoma cells by inducing apoptosis via the PI3K/Akt pathway.

UNBS5162, a novel naphthalimide, is generated by UNBS3157 hydrolysis in physiological saline. In the present study, the effects of UNBS5162 on M14 human melanoma cells were evaluated by Cell Counting Kit­8 and transwell assays, as well as western blotting. The underlying mechanism of apoptosis induced by UNBS5162 was investigated. The results demonstrated that proliferation of UNBS5162­treated M14 melanoma cells was markedly inhibited in a time­dependent manner. The flow cytometry results indicated a markedly increased apoptosis rate in the experimental group compared with in the control group (23.8±0.4 vs. 7.62±0.5%). Microscopy analysis revealed that the invasive and migratory abilities of UNBS5162­treated M14 cells were markedly suppressed. Furthermore, UNBS5162 treatment led to decreased expression of the anti­apoptotic protein B­cell lymphoma 2, but increased expression of the pro­apoptotic proteins Bcl­2­associated X protein and caspase­3. In addition, the expression of several key proteins involved in the phosphatidylinositol­4,5­bisphosphate 3­kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was altered in M14 cells treated with UNBS5162. Based on these results, it may be hypothesized that UNBS5162 suppresses the proliferation of M14 cells by inducing apoptosis via inhibition of key proteins in the PI3K/Akt/mTOR signaling pathway.

Comparative characterization of SHED and DPSCs during extended cultivation in vitro.

Dental pulp stem cells (DPSCs) and stem cells from human exfoliated deciduous teeth (SHED) are types of human dental tissue­derived mesenchymal stem cells (MSCs). These cells possess a capacity for self­renewal, multilineage differentiation potential and immunomodulatory functions. Previous studies have reported that DPSCs and SHED may be beneficial in regenerative treatments and immunotherapy. The substantial expansion of cells in vitro is a prerequisite to obtaining adequate cell numbers required for cell­based therapy. However, the regeneration and clinical potential of MSCs diminishes with long­term cell culture amplification. To assess the alterations in SHED and DPSCs characteristics that underlie cellular senescence and result from extended in vitro amplification, the biological properties of SHED and DPSCs at passages 4 (P4) and 20 (P20) were compared. The cells underwent senescence following serial expansion to P20, as determined by altered cell morphology, decreased proliferation and migration capacity, attenuated differentiation potential, elevated senescence­associated ß­galactosidase (SA­ß­gal)­positive rates and increased apoptosis. The phenotypic changes were also accompanied by a marked increase in the expression of p53, p21 and p16Ink4a. The present study also identified that senescent DPSCs exhibited an increased number of positive cells in SA­ß­gal staining and demonstrated varying expressions of p53, p21 and p16Ink4a in comparison with SHED, indicating the involvement of diverse pathways in cellular senescence during long­term sequential in vitro culture and passage. Furthermore, at early and late passages, SHED exhibited a higher proliferation rate and osteogenic differentiation capability when compared with DPSCs. In addition, both cell types maintained their characteristic immunophenotype during long­term cultivation, while the expression levels of CD73 were higher in SHED at P20. The present study concluded that notable alterations were exhibited in SHED and DPSCs during the process of extensive expansion in vitro and the results may provide guidance for the selection of safe and effective expanded SHED and DPSCs for regenerative medicine and therapy.

Neuroprotective action and mechanistic evaluation of protodioscin against rat model of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the most widespread motor-affecting disease affecting majorly middle- and late age population. Thus, in the current study, we intended to explore the neuroprotective effect of protodioscin (Proto) against 6-hydroxydopamine (6-OHDA)-induced PD rat model. METHODS: After induction of PD with the injection of 6-OHDA, the different dose of Proto was administered for the duration of experimental protocol (2 months). We have scrutinized the consequence of Proto on the cognitive behaviours via Moris water maze (MWM), and recognition of novel objects and its location tasks. The effect of Proto was also investigated on the expression of Nrf2 in human neuroblastoma SHSY5Y cells via western blot analysis. RESULTS: The results showed significant decrease in travelled distance as compared by the lesion treated group. Further significant difference was revealed in the latency time to detect the platform that is visible and it confirmed that, there were no noteworthy dissimilarity was observed in the visual and motor function ability. The result also suggests that, the activation of Nrf2 is the possible mechanism of neuroprotection of Proto against PD. CONCLUSION: As a concluding remark, the present study confirmed the neuroprotective role of Proto against PD both in in vitro and in vivo models.