Knowledge and attitude of spouses of puerperas towards breastfeeding.

OBJECTIVE: To investigate the extent of knowledge about breastfeeding and attitudes towards infant feeding among spouses of puerperas at the time of discharge from hospital, and explore the factors influencing spousal attitudes toward breastfeeding. METHODS: We conducted a questionnaire survey among 204 spouses of puerperas who were admitted in the maternity wards at a tertiary hospital in Shaanxi Province between October 2021 and December 2021. Respondents who fulfilled the inclusion criteria were identified using convenient sampling. RESULTS: (1) The score of breastfeeding knowledge among spouses prior to discharge from the hospital was (10.56 ± 3.78), with an accuracy rate of 59.6%, and the lowest accuracy rate was for Item 1 "Newborns should be fed on time, not on demand" (42.6%) and Item 5 "Breastfeeding can prevent infant rickets" (49.5%). (2) The average score of spouses' infant feeding attitudes was (58.15 ± 5.55), and the lowest scoring was for Item 17 "Daily urine volume of infants is a reliable indicator to judge whether they get enough breast milk" (1.99 ± 1.14). (3) Generalized linear model analysis showed a more positive attitude (higher score) among spousal attitudes towards infant feeding in those who had received breastfeeding education [OR = 4.588, 95% CI (0.160 ∼ 3.598)] and those with a master's degree or above [OR = 18.278, 95% CI (3.471 ∼ 9.346)]. CONCLUSION: (1) Spouses that received breastfeeding education and those that had a Masters Degree and above had more positive attitude towards infant feeding. (2) Medical staff should focus on puerperas'spouses with degrees below master's level who had not received breastfeeding education. We recommend using a variety of education methods to enable them to acquire more knowledge on breastfeeding and develop a more positive attitude towards breastfeeding, which will further enhance spousal support for breastfeeding, thus positivizing postpartum co-parenting attitudes and improving the rate of exclusive breastfeeding.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

PURPOSE: Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. METHOD: The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. RESULTS: After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, ß-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). CONCLUSION: Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Development of a Predictive Model for Optimization of Embryo Transfer Timing Using Blood-Based microRNA Expression Profile.

MicroRNAs (miRNAs) can regulate the expression of genes involved in the establishment of the window of implantation (WOI) in the endometrium. Recent studies indicated that cell-free miRNAs in uterine fluid and blood samples could act as alternative and non-invasive sample types for endometrial receptivity analysis. In this study, we attempt to systematically evaluate whether the expression levels of cell-free microRNAs in blood samples could be used as non-invasive biomarkers for assessing endometrial receptivity status. We profiled the miRNA expression levels of 111 blood samples using next-generation sequencing to establish a predictive model for the assessment of endometrial receptivity status. This model was validated with an independent dataset (n = 73). The overall accuracy is 95.9%. Specifically, we achieved accuracies of 95.9%, 95.9%, and 100.0% for the pre-receptive group, the receptive group, and the post-respective group, respectively. Additionally, we identified a set of differentially expressed miRNAs between different endometrial receptivity statuses using the following criteria: p-value < 0.05 and fold change greater than 1.5 or less than -1.5. In conclusion, the expression levels of cell-free miRNAs in blood samples can be utilized in a non-invasive manner to distinguish different endometrial receptivity statuses.

The effectiveness of the Structured Health Intervention For Truckers (SHIFT): a cluster randomised controlled trial (RCT).

BACKGROUND: Long distance heavy goods vehicle (HGV) drivers exhibit higher than nationally representative rates of obesity, and obesity-related co-morbidities, and are underserved in terms of health promotion initiatives. The purpose of this study was to evaluate the effectiveness of the multicomponent 'Structured Health Intervention For Truckers' (SHIFT), compared to usual care, at 6- and 16-18-month follow-up. METHODS: We conducted a two-arm cluster RCT in transport sites throughout the Midlands, UK. Outcome measures were assessed at baseline, at 6- and 16-18-month follow-up. Clusters were randomised (1:1) following baseline measurements to either the SHIFT arm or usual practice control arm. The 6-month SHIFT programme included a group-based interactive 6-h education and behaviour change session, health coach support and equipment provision (Fitbit® and resistance bands/balls to facilitate a 'cab workout'). The primary outcome was device-assessed physical activity (mean steps/day) at 6 months. Secondary outcomes included the following: device-assessed sitting, physical activity intensity and sleep; cardiometabolic health, diet, mental wellbeing and work-related psychosocial variables. Data were analysed using mixed-effect linear regression models using a complete-case population. RESULTS: Three hundred eighty-two HGV drivers (mean ± SD age: 48.4 ± 9.4 years, BMI: 30.4 ± 5.1 kg/m2, 99% male) were recruited across 25 clusters (sites) and randomised into either the SHIFT (12 clusters, n = 183) or control (13 clusters, n = 199) arms. At 6 months, 209 (55%) participants provided primary outcome data. Significant differences in mean daily steps were found between groups, in favour of the SHIFT arm (adjusted mean difference: 1008 steps/day, 95% CI: 145-1871, p = 0.022). Favourable differences were also seen in the SHIFT group, relative to the control group, in time spent sitting (- 24 mins/day, 95% CI: - 43 to - 6), and moderate-to-vigorous physical activity (6 mins/day, 95% CI: 0.3-11). Differences were not maintained at 16-18 months. No differences were observed between groups in the other secondary outcomes at either follow-up. CONCLUSIONS: The SHIFT programme led to a potentially clinically meaningful difference in daily steps, between trial arms, at 6 months. Whilst the longer-term impact is unclear, the programme offers potential to be incorporated into driver training courses to promote activity in this at-risk, underserved and hard-to-reach essential occupational group. TRIAL REGISTRATION: ISRCTN10483894 (date registered: 01/03/2017).

The structured health intervention for truckers (SHIFT) cluster randomised controlled trial: a mixed methods process evaluation.

BACKGROUND: This paper presents the mixed methods process evaluation of the randomised controlled trial (RCT) of the Structured Health Intervention For Truckers (SHIFT), a multi-component intervention targeting physical activity and positive lifestyle behaviours in a cohort of 382 truck drivers in the UK. The SHIFT RCT found a significant difference in daily steps between intervention and control groups at 6-months in favour of the intervention participants. METHODS: SHIFT was evaluated within a cluster-RCT and involved 25 transport sites (12 intervention and 13 control sites). Intervention components included an education session, Fitbit, text messages, and cab workout equipment. Participants completed questionnaires at baseline and 6-months follow-up. Semi-structured focus groups/interviews were conducted with drivers (n = 19) and managers (n = 18) from each site, after completion of the final follow-up health assessment (16-18 months post-randomisation). Questionnaires and interviews collected information on fidelity, dose, context, implementation, barriers, sustainability, and contamination. RESULTS: Questionnaire and interview data from intervention participants indicated favourable attitudes towards SHIFT, specifically towards the Fitbit with a high proportion of drivers reporting regularly using it (89.1%). 79.2% of intervention participants attended the education session, which was deemed useful for facilitating improvements in knowledge and behaviour change, dietary changes were predominantly recalled. Despite not being part of the intervention, participants reported that feedback from the health assessments motivated them to change aspects of their lifestyle (intervention = 91.1%, control = 67.5%). The cab workout equipment was used less and spoken unfavourably of in the interviews. The main barriers to a healthy lifestyle at work were reported as long hours and irregular shift patterns. The most suggested improvement for the intervention was more frequent contact with drivers. Managers were positive about the objectives of SHIFT, however almost all mentioned the challenges related to implementation, specifically in smaller sites. CONCLUSIONS: Overall, SHIFT was predominantly implemented as intended, with minimal discrepancies seen between the delivery and protocol. Having said this, transport sites each have distinct characteristics, which may require adaptations to individual settings to encourage participation. Managers and drivers reported enthusiasm and necessity for SHIFT to be included in future Certificate of Professional Competence training. TRIAL REGISTRATION: ISRCTN10483894 (date registered: 01/03/2017).

Population-specific cut-off points of fatty liver index: a study based on the National Health and Nutrition Examination Survey data.

BACKGROUND: Fatty liver index (FLI) is the most recognized blood biomarker for diagnosis of hepatic steatosis (HS), but lacks the reliable specific cut-off points (COPs). Therefore, we aim to investigate the population-specific COPs of FLI based on the results of liver ultrasound transient elastography (LUTE) and conventional ultrasonography in the National Health and Nutrition Examination Survey (NHANES). METHODS: 5948 participants who underwent LUTE from the NHANES 2017-2018 and 14,797 participants who underwent conventional ultrasonography from the Third NHANES (NHANES III) were recruited. FLI was calculated by using body mass index (BMI), waist circumference (WC), triglyceride, and gamma-glutamyl transferase, and its optimal COPs in a specific population (stratified by sex, BMI, and WC) were obtained from receiver operator characteristics (ROC) curve with ultrasonic-diagnosed HS as the reference standard. RESULTS: Based on LUTE in NHANES 2017-2018, the prevalence of HS and metabolic dysfunction-associated fatty liver disease (MAFLD) were 58.7% and 56.2%, respectively, and the optimal COP of FLI for HS diagnosis in the overall population was 45.60, with an area under ROC curve (AUROC) of 0.833 (0.822-0.844). Based on conventional ultrasonography in NHANES III, the prevalence of HS and MAFLD were 34.4% and 27. 9%, respectively, and the optimal COP of FLI for HS was 59.5, with an AUROC of 0.681 (0.671-0.691). With the increase of BMI and WC, the COPs increased gradually with significant differences between different groups. Compared with conventional ultrasonography, the COPs of FLI based on LUTE were much more precise, with higher diagnostic ability. The population-specific COPs of FLI stratified by gender, WC, and BMI were tabulated. CONCLUSION: In the United States, the incidences of HS and MAFLD were high, especially when assessed by LUTE. The FLI based on LUTE is well capable of predicting HS when stratified by gender, WC, and BMI.

Sleep duration and sleep efficiency in UK long-distance heavy goods vehicle drivers.

OBJECTIVES: To profile sleep duration and sleep efficiency in UK long-distance heavy goods vehicle (HGV) drivers and explore demographic, occupational and lifestyle predictors of sleep. METHODS: Cross-sectional analyses were carried out on 329 HGV drivers (98.5% men) recruited across an international logistics company within the midland's region, UK. Sleep duration and efficiency were assessed via wrist-worn accelerometry (GENEActiv) over 8 days. Proportions of drivers with short sleep duration (<6 hour/24 hours and <7 hour/24 hours) and inadequate sleep efficiency (<85%) were calculated. Demographic, occupational and lifestyle data were collected via questionnaires and device-based measures. Logistic regression assessed predictors of short sleep duration and inadequate sleep efficiency. RESULTS: 58% of drivers had a mean sleep duration of <6 hour/24 hours, 91% demonstrated <7-hour sleep/24 hours and 72% achieved <85% sleep efficiency. Sleeping <6 hour/24 hours was less likely in morning (OR 0.45, 95% CI 0.21 to 0.94) and afternoon (OR 0.24, CI 0.10 to 0.60) shift workers (vs night) and if never smoked (vs current smokers) (OR 0.45, CI -0.22 to 0.92). The likelihood of sleeping <7 hour/24 hours reduced with age (OR 0.92, CI 0.87 to 0.98). The likelihood of presenting inadequate sleep efficiency reduced with age (OR 0.96, CI 0.93 to 0.99) and overweight body mass index category (vs obese) (OR 0.47, CI 0.27 to 0.82). CONCLUSIONS: The high prevalence of short sleep duration and insufficient sleep quality (efficiency) rate suggest that many HGV drivers have increased risk of excessive daytime sleepiness, road traffic accidents and chronic disease. Future sleep research in UK HGV cohorts is warranted given the road safety and public health implications.

Effects of Mindfulness-Based Therapy for Cancer Patients: A Systematic Review and Meta-analysis.

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.

Divalent nutrient cations: Friend and foe during zinc stress in rice.

Zn deficiency is the most common micronutrient deficit in rice but Zn is also a widespread industrial pollutant. Zn deficiency responses in rice are well documented, but comparative responses to Zn deficiency and excess have not been reported. Therefore, we compared the physiological, transcriptional and biochemical properties of rice subjected to Zn starvation or excess at early and later treatment stages. Both forms of Zn stress inhibited root and shoot growth. Gene ontology analysis of differentially expressed genes highlighted the overrepresentation of Zn transport and antioxidative defense for both Zn stresses, whereas diterpene biosynthesis was solely induced by excess Zn. Divalent cations (Fe, Cu, Ca, Mn and Mg) accumulated in Zn-deficient shoots but Mg and Mn were depleted in the Zn excess shoots, mirroring the gene expression of non-specific Zn transporters and chelators. Ascorbate peroxidase activity was induced after 14 days of Zn starvation, scavenging H2 O2 more effectively to prevent leaf chlorosis via the Fe-dependent Fenton reaction. Conversely, excess Zn triggered the expression of genes encoding Mg/Mn-binding proteins (OsCPS2/4 and OsKSL4/7) required for antimicrobial diterpenoid biosynthesis. Our study reveals the potential role of divalent cations in the shoot, driving the unique responses of rice to each form of Zn stress.

Prevalence of and risk factors for metabolic associated fatty liver disease in an urban population in China: a cross-sectional comparative study.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is a new definition for liver disease associated with known metabolic dysfunction. Based on new diagnostic criteria, we aimed to investigate its prevalence and risk factors in Chinese population. METHODS: We conducted this study in a health examination population who underwent abdominal ultrasonography in China. The diagnosis of MAFLD was based on the new diagnostic criteria. The characteristics of the MAFLD population, as well as the associations between MAFLD and metabolic abnormalities, were explored. Mann-Whitney U test and chi-square test were performed to compare different variables. Binary logistic regression was used to determine the risk factors for MAFLD. RESULTS: Among 139,170 subjects, the prevalence of MAFLD was 26.1% (males: 35.4%; females: 14.1%). The prevalence based on female menopausal status, that is, premenopausal, perimenopausal, and postmenopausal, was 6.1%, 16.8%, and 30.2%, respectively. In different BMI groups (underweight, normal, overweight and obese), the prevalence was 0.1%, 4.0%, 27.4% and 59.8%, respectively. The proportions of abnormal metabolic features in the MAFLD group were significantly higher than those in the non-MAFLD group, as was the proportion of elevated alanine aminotransferase (ALT) (42.5% vs. 11%, P < 0.001). In nonobese individuals with MAFLD, the proportions of abnormal metabolic features were also all significantly higher than those in nonobese individuals without MAFLD. The prevalence of metabolic syndrome (MS), dyslipidaemia, and hyperuricaemia, respectively, in the MAFLD group (53.2%, 80.0%, and 45.0%) was significantly higher than that in the non-MAFLD group (10.1%, 41.7%, and 16.8%). Logistic regression revealed that age, BMI, waist circumference, ALT, triglycerides, fasting glucose, uric acid and platelet count were associated with MAFLD. CONCLUSIONS: MAFLD is prevalent in China and varies considerably among different age, sex, BMI, and female menopausal status groups. MAFLD is related to metabolic disorders, especially obesity, while metabolic disorders also play important roles in the occurrence of MAFLD in nonobese individuals. MAFLD patients exhibit a high prevalence of MS, dyslipidaemia, hyperuricaemia, and elevated liver enzymes. MAFLD tends to coexist with systemic metabolic disorders, and a deep inner relationship may exist between MAFLD and MS. Metabolic disorders should be considered to improve the management of MAFLD.

Incidence and consequences of resuming oral anticoagulant therapy following hematuria and risks of ischemic stroke and major bleeding in patients with atrial fibrillation.

Following hematuria, it is uncertain to what extent a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) is resumed, and the risks of ischemic stroke/systemic embolism and major bleeding associated with NOAC and VKA resumption are unknown. A cohort study was conducted using electronic medical records collected from 2009 to 2017 at a multicenter healthcare provider in Taiwan. The cohort included 4155 atrial fibrillation patients receiving anticoagulant therapy with hematuria (age: 71.4 ± 11.2 years; 48.8% female). Within 90 days following hematuria, 3287 patients (79.1%) resumed oral anticoagulants including VKA (n = 1554, 37.4%) and NOACs (n = 1733, 41.7%), whereas 868 patients did not resume anticoagulant. Follow-up was initiated 90 days after the occurrence of hematuria, and time-varying multiple Cox regression analyses were used for comparisons between the resumption of NOAC and VKA. The event rates per 100 person-years in the VKA resumption and NOAC resumption groups were 3.04 and 3.28 for ischemic stroke/systemic embolism, and 2.63 and 2.92 for major bleeding, respectively. Patients resuming NOAC had similar risks of ischemic stroke/systemic embolism (hazard ratio 1.14, 95% CI 0.75-1.74) and major bleeding (hazard ratio 1.12, 95% CI 0.72-1.74) compared with those resuming VKA. Since 2011, the proportion of NOAC resumption has increased, whereas the proportions of VKA resumption and non-resumption have decreased. In conclusion, more and more patients who suffer a hematuria while on oral anticoagulant therapy resume NOAC. Patients resuming NOAC have similar risks of ischemic stroke/systemic embolism and major bleeding compared with those resuming VKA.

Relationship between the Metabolic Associated Fatty Liver Disease and Endometrial Thickness in Postmenopausal Women: A Cross-sectional Study in China.

Objectives: To determine the relationship between the endometrial thickness (ET) and metabolic associated fatty liver disease (MAFLD) in the postmenopausal women who have a comprehensive health examination. Methods: This was a population-based, retrospective observational study of the prevalence of MAFLD in 8594 postmenopausal women with different ET in the Quality Control Center of Health Examination in Chongqing, China. Binary and multivariable logistic regression analyses were used to obtain odds ratios and 95% confidence intervals for patients of different ET with MAFLD after adjusting for age. Results: The incidences of MAFLD were 28.6% (1352), 30.3% (1058), 34.9% (133) in postmenopausal women with ET of < 3 mm, 3 mm ≤ & < 5 mm, and ≥ 5 mm, respectively. Compared with a baseline ET of less than 5.0 mm, the risk of MAFLD in patients with ET of ≥5.0 mm is higher (OR=1.291, 95% CI: 1.041-1.603, P<0.05). After adjustment for age, a statistically significant positive correlation was still observed. The increased prevalence of MAFLD in patients with ET of 3 mm ≤ &<5 mm (OR=1.110, 95% CI: 1.008-1.223) and ≥5 mm (OR=1.383, 95% CI: 1.109-1.724) achieved statistical significance, respectively. In addition, multiple logistic analyses controlling for age also confirmed the finding of positive correlation among body mass index (BMI) and ET. Conclusion: Our results suggest that there is a positive correlation between MAFLD and ET in postmenopausal women. In addition, increased BMI is also associated with an increased risk of thickened endometrium.

Stand Out in Class: restructuring the classroom environment to reduce sitting time - findings from a pilot cluster randomised controlled trial.

BACKGROUND: Excessive sedentary behaviour (sitting) is a risk factor for poor health in children and adults. Incorporating sit-stand desks in the classroom environment has been highlighted as a potential strategy to reduce children's sitting time. The primary aim of this study was to examine the feasibility of conducting a cluster randomised controlled trial (RCT) of a sit-stand desk intervention within primary school classrooms. METHODS: We conducted a two-armed pilot cluster RCT involving 8 primary schools in Bradford, United Kingdom. Schools were randomised on a 1:1 basis to the intervention or usual practice control arm. All children (aged 9-10 years) in participating classes were eligible to take part. Six sit-stand desks replaced three standard desks (sitting 6 children) in the intervention classrooms for 4.5-months. Teachers were encouraged to use a rotation system to ensure all pupils were exposed to the sit-stand desks for > 1 h/day on average. Trial feasibility outcomes (assessed using quantitative and qualitative measures) included school and participant recruitment and attrition, intervention and outcome measure completion rates, acceptability, and preliminary effectiveness of the intervention for reducing sitting time. A weighted linear regression model compared changes in weekday sitting time (assessed using the activPAL accelerometer) between trial arms. RESULTS: School and child recruitment rates were 33% (n = 8) and 75% (n = 176). At follow-up, retention rates were 100% for schools and 97% for children. Outcome measure completion rates ranged from 63 to 97%. A preliminary estimate of intervention effectiveness revealed a mean difference in change in sitting of - 30.6 min/day (95% CI: - 56.42 to - 4.84) in favour of the intervention group, after adjusting for baseline sitting and wear time. Qualitative measures revealed the intervention and evaluation procedures were acceptable to teachers and children, except for some problems with activPAL attachment. CONCLUSION: This study provides evidence of the acceptability and feasibility of a sit-stand desk intervention and evaluation methods. Preliminary evidence suggests the intervention showed potential in reducing children's weekday sitting but some adaptations to the desk rotation system are needed to maximize exposure. Lessons learnt from this trial will inform the planning of a definitive trial. TRIAL REGISTRATION: ISRCTN12915848 (registered: 09/11/16).

Effectiveness and safety of non-vitamin-K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with thrombocytopenia.

Patients with thrombocytopenia were excluded from major clinical trials that investigated non-vitamin-K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to evaluate the effectiveness and safety of NOAC versus warfarin in AF patients with thrombocytopenia. From 2010 to 2017, a cohort study based on electronic medical records of a multi-center healthcare provider in Taiwan and included 8239 anticoagulated AF patients (age 77.0 ± 7.3 years, 48.0% female). Patients were divided into two subgroups: 7872 patients with a normal platelet count and 367 patients (4.4%) with thrombocytopenia, which was defined as a platelet count less than 100 × 103/µL. We performed Cox proportional hazard analyses to compare the risks of ischemic stroke or systemic embolism (IS/SE), major bleeding, and death between NOAC and warfarin therapies in patients with a normal platelet count and those with thrombocytopenia, respectively. In patients with a normal platelet count, NOAC therapy (n = 4904) was associated with a significantly lower risk of major bleeding, with no difference in the risk of IS/SE or death when compared with warfarin therapy (n = 2968). In patients with thrombocytopenia, NOAC therapy (n = 181) was associated with a lower tendency for major bleeding (aHR 0.45, 95% CI 0.16-1.14) with no significant difference in IS/SE (aHR 0.94, 95% CI 0.29-2.91) or death (aHR 0.95, 95% CI 0.46-1.95) when compared with warfarin therapy (n = 186). NOAC therapy is a reasonable choice for stroke prevention in AF patients with thrombocytopenia.

The RopGEF2-ROP7/ROP2 Pathway Activated by phyB Suppresses Red Light-Induced Stomatal Opening.

Circadian rhythm of stomatal aperture is mainly regulated by light/darkness. Blue and red light induce stomatal opening through different mechanisms that are mediated by special receptors. ROP2, a member of Rho GTPase family in Arabidopsis (Arabidopsisthaliana), has been found to negatively regulate light-induced stomatal opening. However, the upstream guanine nucleotide exchange factor (GEF) RopGEFs have not been revealed, and it is unclear which photoreceptor is required for the action of RopGEFs-ROPs. Here, we showed that RopGEF2 acted as a negative regulator in phytochrome B (phyB)-mediated red light-induced stomatal opening. Meanwhile, ROP7, another member of ROP family, acting redundantly with ROP2, was regulated by RopGEF2 in this process. RopGEF2 interacted with ROP7 and ROP2 and enhanced their intrinsic nucleotide exchange rates. Furthermore, the direct interactions between phyB and RopGEF2 were detected in vitro and in plants, and phyB enhanced the GEF activity of RopGEF2 toward both ROP7 and ROP2 under light. In addition, RopGEF4 functioned redundantly with RopGEF2 in red light-induced stomatal opening by activating both ROP7 and ROP2, and RopGEF2/RopGEF4 acted genetically downstream of phyB; however, the GEF activity of RopGEF4 was not directly enhanced by phyB. These results revealed that red light-activated phyB enhances the GEF activities of RopGEF2 and RopGEF4 directly or indirectly, and then activate both ROP7 and ROP2 in guard cells. The negative mechanism triggered by phyB prevents the excessive stomatal opening under red light.

Small P particles formed by the Taiwan-native norovirus P domain overexpressed in Komagataella pastoris.

The protrusion (P) domain of the major structural protein VP1 of norovirus (NoV) is critical for the host's immune response and receptor binding. Most heterologous P domains expressed in Escherichia coli or Komagataella pastoris (formally known as Pichia pastoris) form P particles consisting of 24 P monomers formed through intermolecular contact in the P regions and an end-linked cysteine tag. The small P particle is only found in P domains with terminal modifications. In this study, the NoV P domain of the most predominant NoV strain GII.4 isolated from Taiwan was expressed in K. pastoris. A high yield of NoV P was obtained using the high-cell density fermentation process in K. pastoris. A large amount of the small P particles and the trimer and dimer complexes formed by 12, 6, and 2 P monomers were observed in both the expression of the NoV P-His and P containing cysteine tag at the N-terminus. Dynamic light scattering and transmission electron microscopy analysis of the purified NoV P-His and P revealed that most of these small P particles are triangle-, square-, and ring-shaped with a diameter of 14-15 nm. The binding ability of purified NoV P-His and P to human histo-blood group antigen was confirmed by a saliva-binding assay. Without terminal modification, small P particles were formed in our study. The amino acid sequence analysis showed only four different amino acids (residue 84, 119, 136, and 313) between the P domain in this study and other investigated GII.4 strains suggesting that these amino acids might play an important role in the P particle formation. The small P particles formed by the Taiwan-native norovirus P domain overexpressed in K. pastoris may provide further information for morphogenesis studies and vaccine development.

[Pharmacokinetics of magnolol and honokiol in Weichang'an pill].

To conduct multiple-reaction monitoring(MRM) quantitative analysis with high-performance liquid chromatography coupled with mass spectrometry method, establish the quantification method of magnolol and honokiol in blood sample under negative ion mode with ibuprofen as internal standard, investigate the pharmacokinetic process of lignans constituents after oral administration of Weichang'an pill(WCA) at different doses, and provide theoretical basis to further reveal the material basis of WCA's anti-diarrhea effect. In the plasma samples, the linear relationship was good over the concentration range of 5.25 to 1 344.00 µg•L ⁻¹ for magnolol and 10.08 to 2 580.00 µg•L ⁻¹ for honokiol. The results of precision, stability, and extraction recovery tests showed that the determination method of plasma concentration for such compositions was stable and reliable. Dose-dependence was shown for magnolol and honokiol in the plasma concentration-time profile. The results indicated that the time to reach the maximum plasma concentration(Tmax) for lignanoids was 0.55-1.42 h, when the maximum plasma concentration(Cmax) could reach 996.36-2 330.96,189.87-1 469.43 µg•L ⁻¹ respectively for magnolol and honokiol. The lignanoids could be absorbed rapidly in the blood after oral administration of WAC pills, providing experimental basis to prove rapid and long-acting anti-diarrhea effect of WAC pills after oral administration.

Phase II Study of Recombinant Antitumor and Antivirus Protein Injection Compared With Placebo in Metastatic Colorectal Cancer After Failure of Standard Treatment.

LESSONS LEARNED: Novaferon showed moderate efficacy and was well-tolerated in patients with metastatic colorectal cancer (mCRC), especially with the 20 µg injected 3 times a week strategy.Although Novaferon did not provide a survival benefit for mCRC patients who have failed standard treatment, it may play a role in improvement of immune function. BACKGROUND: To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens. METHODS: We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 µg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 µg Novaferon injected 3 times per week, (c) 40 µg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival. RESULTS: There was no significant difference in overall survival among the four cohorts. The 20-µg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in the placebo group remained the same. CONCLUSION: Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-µg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients.

Frequent alterations of HER2 through mutation, amplification, or overexpression in pleomorphic lobular carcinoma of the breast.

Mutations in HER2 gene have been identified in a small subset of breast cancer cases. Identification of HER2 mutation has therapeutic implications for breast cancer, but whether a subgroup of breast cancer with a higher frequency of HER2 mutation exists, remains unknown. We analyzed HER2 mutation and pathologic factors on 73 formalin-fixed, paraffin-embedded samples, including 21 pleomorphic invasive lobular carcinoma (p-ILC) cases, 3 pleomorphic lobular carcinoma in situ (p-LCIS) cases, and 49 classic invasive lobular carcinoma (c-ILC) cases. Mutations were identified through direct sequencing. HER2 overexpression and amplification were determined through immunohistochemistry and fluorescent in situ hybridization. Six mutations were identified, including five in the 24 p-ILC or p-LCIS (p-ILC/p-LCIS) cases (20.8 %) and one in the 49 c-ILC cases (2.0 %), and the difference in frequency was significant (p = 0.013). Eight of the 24 (33.3 %) p-ILC/p-LCIS cases exhibited HER2 amplification or overexpression (amplification/overexpression), which was significantly higher than in the c-ILC cases (1/49, 2 %). Mutation and amplification/overexpression were mutually exclusive. HER2 mutations were identified more frequently in the p-ILC/p-LCIS cases with extensive apocrine change (p = 0.018). Combined HER2 alterations through mutation or amplification/overexpression were more frequently identified in p-ILC/p-LCIS cases without estrogen receptor expression. The high frequency (54.1 %, 13/24) of combined HER2 alterations in the p-ILC/p-LCIS cases suggests a crucial role of HER2 in the pathogenesis of p-ILC/p-LCIS. Because of the reported responsiveness of HER2 mutation to anti-HER2 therapy, p-ILC patients without HER2 amplification/overexpression should receive HER2 mutation analysis to identify this therapeutically relevant target.