DNA-free CRISPR-Cas9 gene editing of wild tetraploid tomato Solanum peruvianum using protoplast regeneration.

Wild tomatoes (Solanum peruvianum) are important genomic resources for tomato research and breeding. Development of a foreign DNA-free clustered regularly interspaced short palindromic repeat (CRISPR)-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free CRISPR-Cas9 genome editing system based on an optimized protoplast regeneration protocol of S. peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6), and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProSys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-Ca2+-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type (WT) stock and pollination with WT pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the WT. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding.

Associations of Dietary Anthocyanidins Intake with Bone Health in Children: A Cross-Sectional Study.

PURPOSE: Bone health and body composition share several common mechanisms like oxidative stress and inflammation. Anthocyanins have antioxidant and anti-inflammatory properties. We have reported that anthocyanins are associated with better body composition in children, but the associations with bone health have not been elucidated. We aimed to explore the association of anthocyanins with bone mineral content (BMC) and bone mineral density (BMD) at multiple sites in children. METHODS: In this cross-sectional study, 452 Chinese children aged 6-9 years were recruited. A validated 79-item food frequency questionnaire was used to collect dietary information. BMC and BMD at multiple sites (whole body; whole body excluding head, WBEH; limbs; arms; legs) were measured by dual-energy X-ray. RESULTS: Higher dietary intake of total anthocyanidins (per one standard deviation increase) was associated with a 1.28-13.6 g (1.31-1.60%, compared to median) higher BMC at all sites and a 3.61-6.96 mg (0.65-0.90%) higher BMD at the whole body, WBEH, and arm sites after controlling for a number of possible covariates. The results were similar and more pronounced for cyanidin, but not for delphinidin and peonidin. Higher dietary intake of cyanidin (per one standard deviation increase) was associated with a 1.33-15.4 g (1.48-1.68%) higher BMC at all sites and a 4.15-7.77 mg (0.66-1.00%) higher BMD at all sites except the legs. No statistically significant associations with BMC or BMD were found for dietary intake of delphinidin and peonidin. CONCLUSIONS: Higher dietary intake of total anthocyanidins and cyanidins were associated with higher BMC and BMD in Chinese children.

Development of a Cloud-Based Image Processing Health Checkup System for Multi-Item Urine Analysis.

With the busy pace of modern life, an increasing number of people are afflicted by lifestyle diseases. Going directly to the hospital for medical checks is not only time-consuming but also costly. Fortunately, the emergence of rapid tests has alleviated this burden. Accurately interpreting test results is extremely important; misinterpreting the results of rapid tests could lead to delayed medical treatment. Given that URS-10 serve as a rapid test capable of detecting 10 distinct parameters in urine samples, the results of assessing these parameters can offer insights into the subject's physiological condition. These parameters encompass aspects such as metabolism, renal function, diabetes, urinary tract disorders, hemolytic diseases, and acid-base balance, among others. Although the operational procedure is straightforward, the variegated color changes exhibited in the outcomes of individual parameters render it challenging for lay users to deduce causal factors solely from color variations. Moreover, potential misinterpretations could arise due to visual discrepancies. In this study, we successfully developed a cloud-based health checkup system that can be used in an indoor environment. The system is used by placing a URS-10 test strip on a colorimetric board developed for this study, then using a smartphone application to take images which are uploaded to a server for cloud computing. Finally, the interpretation results are stored in the cloud and sent back to the smartphone to be checked by the user. Furthermore, to confirm whether the color calibration technology can eliminate color differences between different cameras, and also whether the colorimetric board and the urine test strips can perform color comparisons correctly in different light intensity environments, indoor environments that could simulate a specific light intensity were established for testing purposes. When comparing the experimental results to real test strips, only two groups failed to reach an identification success rate of 100%, and in both of these cases the success rate reached 95%. The experimental results confirmed that the system developed in this study was able to eliminate color differences between camera devices and could be used without special technical requirements or training.

Regulatory cascade involving transcriptional and N-end rule pathways in rice under submergence.

The rice SUB1A-1 gene, which encodes a group VII ethylene response factor (ERFVII), plays a pivotal role in rice survival under flooding stress, as well as other abiotic stresses. In Arabidopsis, five ERFVII factors play roles in regulating hypoxic responses. A characteristic feature of Arabidopsis ERFVIIs is a destabilizing N terminus, which functions as an N-degron that targets them for degradation via the oxygen-dependent N-end rule pathway of proteolysis, but permits their stabilization during hypoxia for hypoxia-responsive signaling. Despite having the canonical N-degron sequence, SUB1A-1 is not under N-end rule regulation, suggesting a distinct hypoxia signaling pathway in rice during submergence. Herein we show that two other rice ERFVIIs gene, ERF66 and ERF67, are directly transcriptionally up-regulated by SUB1A-1 under submergence. In contrast to SUB1A-1, ERF66 and ERF67 are substrates of the N-end rule pathway that are stabilized under hypoxia and may be responsible for triggering a stronger transcriptional response to promote submergence survival. In support of this, overexpression of ERF66 or ERF67 leads to activation of anaerobic survival genes and enhanced submergence tolerance. Furthermore, by using structural and protein-interaction analyses, we show that the C terminus of SUB1A-1 prevents its degradation via the N-end rule and directly interacts with the SUB1A-1 N terminus, which may explain the enhanced stability of SUB1A-1 despite bearing an N-degron sequence. In summary, our results suggest that SUB1A-1, ERF66, and ERF67 form a regulatory cascade involving transcriptional and N-end rule control, which allows rice to distinguish flooding from other SUB1A-1-regulated stresses.

Aggregation-Enhanced Sonodynamic Activity of Phthalocyanine-Artesunate Conjugates.

The clinical prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT4 A showed about 60-fold higher sonodynamic ROS generation in the aggregated form than in the disaggregated form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The level of the AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle size of their aggregates. Moreover, biological studies demonstrated that ZnPcT4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.

Effects of Neurofeedback on Fibromyalgia: A Randomized Controlled Trial.

BACKGROUND: Fibromyalgia is a chronic widespread pain condition that is associated with sleep disturbances and cognitive impairments. Neurofeedback has been demonstrated to improve pain, sleep quality, and fatigue. However, few studies have examined the effect of neurofeedback for patients with fibromyalgia. AIM: To determine the effects of neurofeedback on pain intensity, symptom severity, sleep quality, and cognitive function in patients with fibromyalgia. DESIGN: This study was a randomized controlled trial. METHOD: Eighty participants were randomized to a neurofeedback group (N = 60), receiving sensorimotor and alpha rhythm feedback for 8 weeks, or a telephone support group (N = 20). RESULTS: Results from the generalized estimating equation modelling revealed significant group-by-time interactions for Brief Pain Inventory pain severity (B = -1.35, SE = 0.46, p = .003) and pain interference (B = -1.75, SE = 0.41, p < .001), Revised Fibromyalgia Impact Questionnaire total scores (B = -16.41, SE = 3.76, p < .001), sleep onset latency (B = -25.33, SE = 9.02, p = .005), and Psychomotor Vigilance Test error (B = -1.38, SE = 0.55, p = .013) after adjustments for age, sex, duration of illness, and group differences at baseline. CONCLUSIONS: An 8-week neurofeedback training regimen of sensorimotor rhythm and alpha brain waves significantly improved pain severity and interference, fibromyalgia symptom severity, sleep latency, and sustained attention in patients with fibromyalgia.

HOme-based Longitudinal Investigation of the multidiSciplinary Team Integrated Care (HOLISTIC): protocol of a prospective nationwide cohort study.

BACKGROUND: The use of home health care (HHC) is increasing worldwide. This may have an impact not only on patients and their caregivers' health but on care resource utilization and costs. We lack information on the impact of HHC on the broader dimensions of health status and care resource utilization. More understanding of the longitudinal HHC impact on HHC patients and caregivers is also needed. Moreover, we know little about the synergy between HHC and social care. Therefore, the present study aims to observe longitudinal changes in health, care resource utilization and costs and caregiving burden among HHC recipients and their caregivers in Taiwan. METHODS: A prospective cohort study "Home-based Longitudinal Investigation of the Multidisciplinary Team Integrated Care (HOLISTIC)" will be conducted and 600 eligible patient-caregiver dyads will be recruited and followed with comprehensive quantitative assessments during six home investigations over two years. The measurements include physical function, psychological health, cognitive function, wellbeing, shared decision making and advance care planning, palliative care and quality of dying, caregiving burden, continuity and coordination of care, care resource utilization, and costs. DISCUSSION: The HOLISTIC study offers the opportunity to comprehensively understand longitudinal changes in health conditions, care resource utilization and costs and caregiving burden among HHC patients and caregivers. It will provide new insights for clinical practitioners and policymakers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier is NCT04250103 which has been registered on 31st January 2020.

Preoperative Stoma Site Marking Decreases Stoma and Peristomal Complications: A Meta-analysis.

PURPOSE: We systematically reviewed the literature in order to determine whether evidence indicated that preoperative stoma site marking reduces the occurrence of postoperative stoma and peristomal complications. DESIGN: Systematic review with meta-analysis of pooled findings. SUBJECTS/SETTING: We systematically reviewed 6 electronic databases including PubMed, MEDLINE, CINAHL, Cochrane Library for English language articles, along with the Airiti Library and Wanfang Data for Chinese articles for evidence related to the effects of stoma site marking on stoma and peristomal complications. We sought articles published from their inception to January 31, 2018. METHODS: Ten studies that included 2109 participants, each comparing 2 groups of patients who did and did not undergo preoperative stoma site marking, were retrieved and analyzed. RESULTS: In patients who underwent stoma site marking, the marking was associated with reduced stoma and peristomal complications in all stoma types (odds ratio [OR] = 0.52; 95% CI, 0.42-0.64; P < .001). Patients who underwent stoma and had fecal ostomies experienced fewer complications (OR = 0.34; 95% CI, 0.25-0.47; P < .001) than patients with unmarked stomas. In contrast, patients with urostomies did not experience fewer complications when compared to those with unmarked ostomies (OR = 0.531; 95% CI, 0.23-1.21; P = .132). Persons with fecal ostomies also had fewer hernias and peristomal skin complications (ORs = 0.25 and 0.30; 95% CIs, 0.09-0.71 and 0.20-0.44, respectively; both Ps < .001). The results revealed that stoma site marking was associated with reduced early and late stoma and peristomal complications (ORs = 0.76 and 0.38; 95% CIs, 0.61-0.94 and 0.32-0.46; P = .010 and P < .001, respectively). CONCLUSIONS: Preoperative stoma site marking is associated with a reduced occurrence of stoma and peristomal complications and should be considered as a standard of preoperative care.

Subjective sleep quality as a mediator in the relationship between pain severity and sustained attention performance in patients with fibromyalgia.

Pain severity and sleep are associated with cognitive performance in patients with fibromyalgia. This study examined whether sleep mediates the relationships of pain severity with psychomotor vigilance and attention in patients with fibromyalgia by analysing 80 patients with fibromyalgia. Cognitive performance, pain severity and sleep parameters were determined using the Psychomotor Vigilance Task, Brief Pain Inventory-Short Form and sleep diaries of seven consecutive nights, respectively. The patients' demographic data were analysed for potential confounding factors. After adjustment for these confounders, a series of regression analyses was performed to examine the mediating role of sleep. The results indicated that higher pain severity was strongly associated with poorer sustained attention and lower sleep quality, the total effects of pain severity on psychomotor vigilance and attention were significant (c path: ß = 0.23, p = 0.04), and pain severity was a significant sleep quality predictor (a path: ß = -0.33, p < 0.01). When sleep quality was entered into the regression model (a × b path), the effects of pain severity on psychomotor vigilance and attention became non-significant (c' path: ß = 0.15, p = 0.20) after adjustment of age, indicating a complete mediating effect of sleep quality in the pain severity-cognitive performance relationship. In conclusion, sleep quality mediates the pain severity-cognitive performance relationship: pain affects sleep quality, which in turn impairs sustained attention. Our findings provide further insight into the processes underlying the relationship between pain and poor cognitive function. Improved sleep quality may offset the detrimental effects of pain on sustained attention.

Effects of napping on cognitive function modulation in elderly adults with a morning chronotype: A nationwide survey.

Circadian rhythms and napping habits have been associated with cognitive function; however, little is known about the interaction effects on cognitive function. The present study examined the moderating effects of napping habits on the relationship between chronotypes and cognitive function decline in elderly adults. This cross-sectional study analysed data from the 2009 Taiwan National Health Interview Survey. A total of 1,724 elderly adults (aged ≥65 years) were included. Cognitive function was determined by the Mini-Mental State Examination. Participants' chronotypes were assessed using the midpoint of sleep. Napping habits were assessed by self-report questions. Demographic data, health-related factors and sleep characteristics of the participants were also assessed as potential confounding factors. A hierarchical regression will be used to test the moderating role of napping habits in the relationship between chronotype and cognitive function level after adjustment for potential confounders. A significant interaction effect between chronotype and napping habits was observed with the MMSE score (b = -0.29, SE = 0.14, p = 0.03). Morning-type elderly patients with nap durations >60 min exhibited significantly higher MMSE scores than non-nappers (F = 7.48; p = 0.00). This nationwide survey confirms that in morning-type elderly adults, nap durations >60 min are associated with less cognitive decline; however, napping habits are not associated with cognitive function level in evening-type and intermediate-type elderly adults.

Cognitive Impairment in Fibromyalgia: A Meta-Analysis of Case-Control Studies.

OBJECTIVE: Cognitive dysfunction has been reported in individuals with fibromyalgia. However, findings regarding cognitive function examined using neuropsychological tests have been inconsistent. The aim of the study was to determine domain-specific cognitive impairment in patients with fibromyalgia compared with healthy controls. METHODS: We conducted a meta-analysis that systematically searched six databases (PubMed, Ovid MEDLINE, Embase, CINAHL, PsycINFO, and Web of Science) for articles published before September 2017. RESULTS: Twenty-three case-control studies with a total of 2096 participants were included in the meta-analysis. Cognitive function was significantly lower (g = 0.87, 95% confidence interval [CI] = 0.60-1.15) in individuals with fibromyalgia than in healthy controls. Large effect sizes were found in learning/memory and attention/psychomotor speed (g = 0.94, p = .013; g = 1.22, p < .001, respectively); medium effect sizes were reported in executive function and working memory (g = 0.72, p < .001; g = 0.75, p < .001, respectively). Depression and anxiety scores were associated with the effect size of group differences in cognitive function (B = 0.11, p < .001, 95% CI = 0.09-0.13; B = 0.02, p < .001, 95% CI = 0.01-0.02, respectively). CONCLUSIONS: Cognitive impairment across different cognitive domains was found in individuals with fibromyalgia compared with healthy controls. Mood states (depression and anxiety) may explain the heterogeneity across studies.

[Prevalence of human papilloma virus infection and its risk factors in some rural areas of Jiangsu, China].

OBJECTIVE: To investigate human papilloma virus (HPV) infection in the male genital tract and its risk factors in some rural areas of Jiangsu Province. METHODS: This study included 398 men from six rural areas in Jiangsu Province, whose female partners, based on the results of cervical cytological examination, were divided into a normal (n = 104), a cervical intraepithelial neoplasia grade Ⅰ (CIN-Ⅰ, n = 100), a CIN-Ⅱ (n = 95), and a CIN-Ⅲ group (n = 99). We examined the male subjects for genital warts and other lesions, collected urethral swab samples for HPV detection, and obtained their sociodemographic data by questionnaire investigation. RESULTS: No megascopic lesions were observed in the genitals of the 398 participants. The total prevalence rate of HPV infection was 11.31% and that of high-risk HPV was 8.54%. Logistic regression analysis showed that daily cleaning of the genitals significantly decreased the risk of HPV infection (OR = 3.030, P = 0.003). CONCLUSIONS: There is a relatively high prevalence rate of recessive infection of genital HPV among the seemingly healthy males in the rural area of Jiangsu Province. Daily cleaning of the genitals may be a protective measure against HPV infection.

[Simultaneous determination of sivelestat and its metabolite XW-IMP-A in human plasma using HPLC-MS/MS].

A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol · L(-1) ammonium acetate at a flow rate of 0.7 mL · min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng · mL(-1) for sivelestat, and 2.50-1000 ng · mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng · mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers.

Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice.

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

AIM: To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. METHODS: This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. RESULTS: There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. CONCLUSION: Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

Comparison of continuous 24-hour and 14-day ECG monitoring for the detection of cardiac arrhythmias in patients with ischemic stroke or syncope.

BACKGROUND: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective. HYPOTHESIS: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope. METHODS: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured. RESULTS: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope. CONCLUSIONS: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF.

Nurse-led coaching of shared decision-making for wound treatment of pressure injury: A pilot study of a randomized trial.

Objectives: International guidelines for managing pressure injury (PI) and ulcers recommend that family members and caregivers should be involved in making decisions for appropriate wound care. However, the effect of shared decision-making (SDM) in the context of PI remains unknown. This study investigated the efficacy of nurse-led medical SDM for PI treatment. Materials and Methods: We constructed a patient decision aid (PDA) for PI treatment on the basis of nursing evidence. Subsequently, we conducted a pilot randomized controlled trial to evaluate the efficacy of SDM compared with that of usual care (control group, [CG]) for PI treatment. Participants with stage 3, stage 4, or unstageable PI were included and randomized into two groups. In the SDM group (SDMG), 10 participants received the SDM intervention for PI before treatment. All participants were followed up for 4 weeks. Primary outcomes were measured using the nine-item SDM Questionnaire (SDM-Q-9) and Decisional Conflict Scale (DCS). Secondary outcomes included wound size and cost of wound management. Results: The expert validity (medical professors and general population) of the PDA designed for PI was measured, and the content validity index was 0.96-0.97. A total of 20 participants were enrolled (10 received SDM and 10 received usual care). The mean age of the participants was 55.7 ± 8.8 years. No significant difference in baseline characteristics (sex, age, staging, or wound area) was observed between the two groups. The SDMG had higher SDM-Q-9 (P < 0.001) and DCS (P < 0.01) scores than did the CG. For the secondary outcomes, the SDMG had a decreased change of wound size and lower wound management costs than did the CG; nevertheless, the differences were not statistically significant. Conclusion: We constructed a PDA for PI treatment, which can be applied in clinical care. The pilot test results revealed that the participants had a lower cost related wound treatment and decreasing wound size in SDMG than CG after the intervention of SDM-PI for 4 weeks. In the future, clinical studies should conduct large-scale randomized trials based on the results of this pilot study.

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson's disease: A meta-analysis.

BACKGROUND: Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events. RESULTS: Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). CONCLUSIONS: Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

Synergistic Anti-Tumor Effect of Toosendanin and Paclitaxel on Triple-Negative Breast Cancer via Regulating ADORA2A-EMT Related Signaling.

Triple negative breast cancer (TNBC) is an aggressive cancer with very poor prognosis. Combination therapy has proven to be a promising strategy for enhancing TNBC treatment efficacy. Toosendanin (TSN), a plant-derived triterpenoid, has shown pleiotropic effects against a variety of tumors. Herein, it is evaluated whether TSN can enhance the efficacy of paclitaxel (PTX), a common chemotherapeutic agent, against TNBC. It is found that TSN and PTX synergistically suppress the proliferation of TNBC cell lines such as MDA-MB-231 and BT-549, and the combined treatment also inhibits the colony formation and induces cell apoptosis. Furthermore, this combination shows more marked migratory inhibition when compared to PTX alone. Mechanistic study shows that the ADORA2A pathway in TNBC is down-regulated by the combination treatment via mediating epithelial-to-mesenchymal transition (EMT) process. In addition, the combined treatment of TSN and PTX significantly attenuates the tumor growth when compared to PTX monotherapy in a mouse model bearing 4T1 tumor. The results suggest that combination of TSN and PTX is superior to PTX alone, suggesting that it may be a promising alternative adjuvant chemotherapy strategy for patients with TNBC, especially those with metastatic TNBC.

Case Report: Imaging features of a new type double inferior vena cava malformation and review.

Background: Double inferior vena cava (DIVC) is a rare vascular malformation. With advances in radiological techniques and diagnosis, more and more types of DIVC were identified and diagnosed. Recognition of the variety of DIVC seen on imaging is essential for subsequent venous interventions. Case presentation: A 77-year-old man presented with low back pain with left lower limb pain for 1 month. Scattered petechiae above the skin surface on the left lower leg, especially on the extensor surface, with flaking and mild tingling of the skin, were noted 3 weeks ago. Ultrasound revealed deep vein thrombosis (DVT) in the left lower limb. Computed tomography pulmonary angiography (CTPA) suggested no significant thrombus in the pulmonary artery. Computed tomography venography (CTV) of bilateral lower limbs showed that iliac vein compression syndrome with formation of deep and superficial venous traffic branches in bilateral lower limbs, predominantly on the left side. CTV of the inferior vena cava (IVC) suggested that the left common iliac vein crossed the common iliac artery bifurcation from dorsal to ventral and continued to travel cranially as a ventral vessel, and connected with the ventral IVC anterior to the right common iliac artery. The right common iliac vein extended cephalad as a dorsal vessel, which was narrowed at the level of 4th lumbar vertebra by compression of the hyperplastic bone and the osteophyte. The patient was discharged after right and left common iliac vein angiography and balloon dilation of bilateral common iliac vein. Conclusion: The formation of both ventrally and dorsally aligned DIVC is rarer. It should be clarified the effects of DIVC on DVT formation, and the importance of imaging for preoperative planning.