A Chinese patent medicine's long-term efficacy on non-dialysis patients with CKD stages 3-5: a retrospective cohort study.

Background: Chinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3-5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear. Methods: Patients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules. Results: A total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were -0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were -0.207 (95% CI: -0.346, -0.068, p = 0.004), -0.214 (95% CI: 0.389, -0.039, p = 0.017), -0.324 (95% CI: 0.538, -0.109, p = 0.003), -0.502 (95% CI: 0.761, -0.243, p = 0.000), and -0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489-0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)). Conclusion: The long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%.

Lipid parameters, adipose tissue distribution and prognosis prediction in chronic kidney Disease patients.

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.

Generation of a whole-brain hemodynamic response function and sex-specific differences in cerebral processing of mechano-sensation in mice detected by BOLD fMRI.

BOLD fMRI has become a prevalent method to study cerebral sensory processing in rodent disease models, including pain and mechanical hypersensitivity. fMRI data analysis is frequently combined with a general-linear-model (GLM) -based analysis, which uses the convolution of a hemodynamic response function (HRF) with the stimulus paradigm. However, several studies indicated that the HRF differs across species, sexes, brain structures, and experimental factors, including stimulation modalities or anesthesia, and hence might strongly affect the outcome of BOLD analyzes. While considerable work has been done in humans and rats to understand the HRF, much less is known in mice. As a prerequisite to investigate mechano-sensory processing and BOLD fMRI data in male and female mice, we (1) designed a rotating stimulator that allows application of two different mechanical modalities, including innocuous von Frey and noxious pinprick stimuli and (2) determined and statistically compared HRFs across 30 brain structures and experimental conditions, including sex and, stimulus modalities. We found that mechanical stimulation lead to brain-wide BOLD signal changes thereby allowing extraction of HRFs from multiple brain structures. However, we did not find differences in HRFs across all brain structures and experimental conditions. Hence, we computed a whole-brain mouse HRF, which is based on 88 functional scans from 30 mice. A comparison of this mouse-specific HRF with our previously reported rat-derived HRF showed significantly slower kinetics in mice. Finally, we detected pronounced differences in cerebral BOLD activation between male and female mice with mechanical stimulation, thereby exposing divergent processing of noxious and innocuous stimuli in both sexes.

Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Association between Anemia Severity and Ischemic Stroke Incidence: A Retrospective Cohort Study.

Stroke patients presenting with anemia at the time of stroke onset had a higher risk of mortality and development of other cardiovascular diseases and comorbidities. The association between the severity of anemia and the risk of developing a stroke is still uncertain. This retrospective study aimed to evaluate the association between stroke incidence and anemia severity (by WHO criteria). A total of 71,787 patients were included, of whom 16,708 (23.27%) were identified as anemic and 55,079 patients were anemia-free. Female patients (62.98%) were more likely to have anemia than males (37.02%). The likelihood of having a stroke within eight years after anemia diagnosis was calculated using Cox proportional hazard regression. Patients with moderate anemia had a significant increase in stroke risk compared to the non-anemia group in univariate analyses (hazard ratios [HR] = 2.31, 95% confidence interval [CI], 1.97-2.71, p < 0.001) and in adjusted HRs (adj-HR = 1.20, 95% CI, 1.02-1.43, p = 0.032). The data reveal that patients with severe anemia received more anemia treatment, such as blood transfusion and nutritional supplementation, and maintaining blood homeostasis may be important to preventing stroke. Anemia is an important risk factor, but other risk factors, including diabetes and hyperlipidemia, also affect stroke development. There is a heightened awareness of anemia's severity and the increasing risk of stroke development.

An investigation of low-protein diets' qualification rates and an analysis of their short-term effects for patients with CKD stages 3-5: a single-center retrospective cohort study from China.

BACKGROUND: The feasibility and efficacy of low-protein diets (LPD) treatment in chronic kidney disease (CKD) is controversial. Based on the characteristics of the Chinese diet, we observe the qualification rates and short-term clinical effects of LPD for CKD patients in our center. METHODS: This is a retrospective cohort study. CKD stages 3-5 patients who were regularly followed up 5 times (over 2 years) and treated with LPD were included. We collected clinical data to observe the changes in LPD qualification rates and divided patients into LPD and non-LPD group according to the average dietary protein intake (DPI) of 5 follow-up time points and compared the changes in primary and secondary outcome measures between the two groups. RESULTS: We analyzed data from 161 eligible CKD stages 3-5 patients. From baseline to the 5th follow-up time point, the LPD qualification rates of all patients were 11.80%, 35.40%, 47.82%, 53.43% and 54.04%, respectively. For primary outcome measures, the urine protein/creatinine ratio (UPCR) decreased more in the LPD group than in the non-LPD group [Median (interquartile range, IQR) of the difference between the 5th follow-up time point and baseline: 0.19 (- 0.01-0.73) vs. 0.10 (- 0.08-0.27), P < 0.001]. We constructed three classes of mixed linear models (model I, II, III). The UPCR slopes were all negative in the LPD group and positive in the non-LPD group (P < 0.001). Meanwhile, in model I, the estimate glomerular filtration rate(eGFR) decline slope in the LPD group was lower than that in the non-LPD group [slope (standard error): - 1.32 (0.37) vs. - 2.35 (0.33), P = 0.036]. For secondary outcome measures, body mass index (BMI) triglycerides (TG), body weight, and fat free mass (FFM) showed stable statistical differences in the comparison of LPD and non-LPD groups, with greater declines in the former. CONCLUSION: The results of this study suggest that LPD treatment can reduce UPCR in patients with CKD stages 3-5, and may also delay the decline in eGFR. Meanwhile, it also reduces BMI, TG, body weight, and FFM, thus the need to prevent malnutrition in clinical implementation.

Formation of Para-H2O by Vacuum-UV Photolysis of O2 in Solid Hydrogen: Implication for Astrochemistry.

The observation that the ortho to para ratio (OPR) of interstellar H2O is smaller than 3 is an important yet unresolved subject in astronomy. We irradiated O2 embedded in solid H2 at 3 K with vacuum-ultraviolet (VUV) light and observed IR lines associated with para-H2O (denoted as pH2O) and nonrotating H2O-(oH2)n (where oH2 denotes ortho-H2) but no lines associated with ortho-H2O (denoted as oH2O). After maintaining the matrix in darkness for ∼30 h, the amount of pH2O decreased, accompanied by an increase in H2O-(oH2)n via diffusion of oH2. After that, the continuous nuclear-spin conversion from oH2 to para-H2 (denoted as pH2) in solid H2 over time resulted in the conversion of nonrotating H2O-(oH2)n to rotating pH2O in solid pH2. The observation of the formation and conversion of pH2O in our experiment suggests a plausible route in which VUV irradiation of O2 and H2 adsorbed on grain surfaces might be responsible for the smaller OPR of interstellar H2O.

Quzhi Formula Alleviates Nonalcoholic Steatohepatitis by Impairing Hepatocyte Lipid Accumulation and Inflammation via Bip/eIF2α Signaling.

Background and Aims: The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH. Methods: A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism. Results: The positive contribution of the Quzhi formula on NASH was confirmed in vivo and in vitro. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling. Conclusions: The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.

The impact of body mass index on clinicopathological features of nonalcoholic fatty liver disease in Taiwan.

BACKGROUND AND AIM: The aim of this study was to assess the impact of body mass index (BMI) on the clinical and histological characteristics of patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled from 2007 to 2019. For comparison, all of the patients were divided into lean body mass (< 23 kg/m2 ), overweight (23-24.9 kg/m2 ), and obesity (BMI â‰§ 25 kg/m2 ). RESULTS: A total of 572 patients with histologically confirmed NAFLD, including 40 (6.99%) lean body mass, 54 (9.44%) overweight, and 478 (83.57%) obese patients, were recruited. Obese NAFLD patients had significantly higher grade of steatosis (grade 3: 29.92% vs 22.22% vs 12.5%, P < 0.0001) and hepatocyte ballooning (grade 2: 14.85% vs 12.96% vs 12.5%, P < 0.0001) than overweight and lean NAFLD patients. The prevalence of nonalcoholic steatohepatitis (NASH) was 22.5%, 25.93%, and 36.19% in lean, overweight, and obese NAFLD patients, respectively. Obesity was significantly associated with fibrosis severity (P = 0.03). The fibrosis index based on four factors (FIB-4) score can identify NAFLD patients without significant fibrosis or with cirrhosis. The areas under the receiver-operating characteristic curve of FIB-4 score to identify patients without significant fibrosis or with cirrhosis were 0.82 (95% confidence interval [CI]: 0.69-0.96) and 0.87 (95% CI: 0.76-0.99) in lean patients; 0.77 (95% CI: 0.61-0.93) and 0.81 (95% CI: 0.59-1.0) in overweight patients; and 0.77 (95% CI: 0.72-0.82) and 0.89 (95% CI: 0.85-0.92) in obese patients. CONCLUSIONS: The majority of NAFLD patients are obese, as defined by BMI. Obesity was significantly associated with NASH and hepatic fibrosis severity in patients with NAFLD.

Developing and validating a prognostic prediction model for patients with chronic kidney disease stages 3-5 based on disease conditions and intervention methods: a retrospective cohort study in China.

OBJECTIVES: To develop and validate a nomogram model to predict chronic kidney disease (CKD) stages 3-5 prognosis. DESIGN: A retrospective cohort study. We used univariate and multivariate Cox regression analysis to select the relevant predictors. To select the best model, we evaluated the prediction models' accuracy by concordance index (C-index), calibration curve, net reclassification index (NRI) and integrated discrimination improvement (IDI). We evaluated the clinical utility by decision curve analysis. SETTING: Chronic Disease Management (CDM) Clinic in the Nephrology Department at the Guangdong Provincial Hospital of Chinese Medicine. PARTICIPANTS: Patients with CKD stages 3-5 in the derivation and validation cohorts were 459 and 326, respectively. PRIMARY OUTCOME MEASURE: Renal replacement therapy (haemodialysis, peritoneal dialysis, renal transplantation) or death. RESULTS: We built four models. Age, estimated glomerular filtration rate and urine protein constituted the most basic model A. Haemoglobin, serum uric acid, cardiovascular disease, primary disease, CDM adherence and predictors in model A constituted model B. Oral medications and predictors in model A constituted model C. All the predictors constituted model D. Model B performed well in both discrimination and calibration (C-index: derivation cohort: 0.881, validation cohort: 0.886). Compared with model A, model B showed significant improvement in the net reclassification and integrated discrimination (model A vs model B: NRI: 1 year: 0.339 (-0.011 to 0.672) and 2 years: 0.314 (0.079 to 0.574); IDI: 1 year: 0.066 (0.010 to 0.127), p<0.001 and 2 years: 0.063 (0.008 to 0.106), p<0.001). There was no significant improvement between NRI and IDI among models B, C and D. Therefore, we selected model B as the optimal model. CONCLUSIONS: We constructed a prediction model to predict the prognosis of patients with CKD stages 3-5 in the first and second year. Applying this model to clinical practice may guide clinical decision-making. Also, this model needs to be externally validated in the future. TRIAL REGISTRATION NUMBER: ChiCTR1900024633 (http://www.chictr.org.cn).

Self-management program for patients with chronic kidney disease (SMP-CKD) in Southern China: protocol for an ambispective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health problem. Short-term self-management has been considered to effect some renal and psychological endpoints. However, there are currently very few studies about self-management for CKD that a) have been scientifically designed by a theory-based framework and b) that evaluate the long-term effects and working mechanism. This study presents the rationale and design of a theory-based cohort study to explore how this self-management intervention works and its effectiveness on the Chinese CKD population. METHODS: In this ambispective intervention cohort study,1,200 patients with CKD stages 1-5 will be recruited from July 2015 to July 2024 in 3 branches of Guangdong Provincial Hospital of Chinese Medicine (GPHCM) in Guangdong province, China. The patients in the self-management cohort will choose to receive an intervention that consists of education, nutrition/diet modification, lifestyle change recommendation, medication review, and psychology support based on Social Cognition Theory (SCT). The patients in the control cohort will do regular follow-ups based on the clinic rules. All the patients will be followed up for 5 years, or until the occurrence of a primary outcome. Detailed clinical, laboratory markers, nutritional status, psychological exposures and outcome questionaries will be collected semiannually in CKD stage 1-2 and trimonthly in stage 3-5 patients. The primary outcome is the occurrence of composite clinical endpoints (doubling of serum creatinine level, ESKD, loss of renal function (≥ 40% decline in GFR from baseline), death, major cardiovascular or cerebrovascular events). The main secondary outcomes include the absolute change and slope of eGFR, absolute changes of urinary protein creatinine ratio, 24-h urine proteinuria, intact parathyroid hormone level, and self-management adherence rate and quality of life from baseline to end of the study. The effectiveness of self-management will be analyzed and the association between longitudinal trajectories of self-management and renal outcomes will be evaluated. DISCUSSION: This study aims to provide further evidence for the effectiveness of theory-based self-management in CKD patients and to improve the lives of patients with CKD by slowing progression, improving psychological well-being and overall quality of life. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR1900024633). 19 July, 2019. http://www.chictr.org.cn/showproj.aspx?proj=38378.

Applying Healthcare Failure Mode and Effect Analysis and the Development of a Real-Time Mobile Application for Modified Early Warning Score Notification to Improve Patient Safety During Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis are a high-risk population. This study identified possible errors by using a healthcare failure mode and effect analysis system to improve patient safety during hemodialysis. METHODS: A multidisciplinary collaborative team, including physicians, nurses, information technicians, and medical staff members, was assembled. A flow diagram was used to indicate each process of the hemodialysis procedure from evaluating patient condition to transporting the patient back to the ward from the hemodialysis center. We scored all possible failure modes using the hazard scoring method as a combination of the occurrence frequency and severity. These potential failure modes were used to identify and evaluate possible risks by using a risk scoring matrix. RESULTS: Thirty failure modes were identified across 6 processes, and their potential causes were explored. Four major strategies for addressing most of the failure modes were implemented: establishment of a mobile application that sends real-time automated alerts to the medical team based on the Modified Early Warning Score, design of a modified dialysis Identify-Situation-Background-Assessment-Recommendation checklist for dialysis, technician education and training, and internal auditing and monitoring of the implementation of the entire process. After the implementation of the strategies, the hazard scores of patients during dialysis dropped by 71.2% from 170 points to 49 points. CONCLUSIONS: The healthcare failure mode and effect analysis system was useful for evaluating potential risk during dialysis. Using the mobile application reduced the occurrence of emergency resuscitation during hemodialysis and significantly improved the communication between medical personnel.

Is E-Version Transition of the Medication Adherence Scale Feasible for CKD Management? A Pilot Study.

BACKGROUND: To transfer a paper-version Chinese and Western medication adherence scale for CKD into an electronic scale, and evaluate its validity, internal consistency and clinical implementation, and assess whether the transition is feasible in clinic. METHODS: We built an e-version Chinese and Western medication adherence scale based on the Wen-JuanXing platform. CKD subjects' responses were applied to test the scale's validity and internal consistency. We retested some of the participants two weeks later randomly. We also tested the clinical application. RESULTS: Of the 434 recruited patients, 228 responded. In exploratory factor analysis (EFA), the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy = 0.8 and Bartlett's approx. Chi-Square = 1340.0 (df = 105, p < 0.001). We extracted four common factors which could explain 61.47% of the variance. However, Item 15 "Have you changed a traditional Chinese medicine prescription yourself within the past month?" had factor loading = 0.3 and measure of sampling adequacy (MSA) = 0.5, meaning we could not enter it into the factor analysis. The internal consistency reliability for medication adherence was 0.9, with a Guttman split-half coefficient = 0.5 and a Spearman-Brown coefficient = 0.6. Cronbach's α was 0.9, 0.4 and 0.5 for the knowledge, belief and behavior domains, respectively. The correlation coefficient r of the test-retest reliability was -0.8 and was -0.8, 0.4, -0.3 in the knowledge, belief and behavior domains, respectively. Patients with comorbidities were more likely to respond. We detected no other significant differences in the clinical profiles between respondents and non-respondents. CONCLUSION: The e-version Chinese and Western medication adherence scales have undesirable construct validity and internal consistency. Thus, caution is needed in transitioning the paper-version scale into an e-version.

Effects of Different Surfactant Charges on the Formation of Gold Nanoparticles by the LASiS Method.

The laser ablation synthesis in solution (LASiS) method has been widely utilized due to its significant prospects in laser microprocessing of nanomaterials. In this study, the LASiS method with the addition of different surfactant charges (cationic CTAB, nonionic TX-100, and anionic SDS) was used to produce Au NPs. An Nd:YAG laser system at 532 nm excitation with some synthetic parameters, including different laser fluences, ablation times, and surfactant concentrations was performed. The obtained Au NPs were characterized by UV-Vis spectroscopy, transmission electron microscopy, and zeta potential analyzer. The Au NPs exhibited the maximum absorption peak at around 520 nm for all samples. The color of Au NPs was changed from red to reddish by increasing the laser fluence. The surfactant charges also played different roles in the Au NPs' growth during the synthesis process. The average sizes of Au NPs were found to be 8.5 nm, 5.5 nm, and 15.5 nm with the medium containing CTAB, TX-100, and SDS, respectively. Besides, the different surfactant charges induced different performances to protect Au NPs from agglomeration. Overall, the SDS and CTAB surfactants exhibited higher stability of the Au NPs compared to the Au NPs with TX-100 surfactant.

Validity, reliability, and application of the electronic version of a chronic kidney disease patient awareness questionnaire: a pilot study.

OBJECTIVES: A questionnaire which provides desirable reliability and validity has been previously developed to assess the disease awareness of diagnosed chronic kidney disease (CKD) patients. However, conventional paper questionnaires often have disadvantages, including recall bias. To substantially improve this, we therefore aimed to explore the feasibility of developing a smartphone-based electronic version (e-version) based upon its original paper version and subsequently tested its validity, reliability, and applicability. METHODS: A pilot study was conducted at Guangdong Provincial Hospital of Chinese Medicine in Guangzhou, China, during August 2019. The e-version had identical content to the paper version and was adapted in terms of layout and assisted functions via the Wechat-incorporated Wen-Juan-Xing platform. Eligible patients with diagnosed CKD were invited to participate and were assigned the e-version. Randomly selected respondents received a test-retest of the same e-version 2 weeks after their first completion. In some instances, psychometric properties, including validity and reliability of the e-version, were examined. In others, its clinical application was also tested, which included comparisons among the clinical profiles of patients who had/had not responded to the questionnaire as well as patients with above or below average questionnaire scores. RESULTS: Of the 225 patients screened, 217 were enrolled to participate, with a response rate of 52.5%. Desirable reliability (Cronbachα = 0.962, ICC for total scores = 0.948), while good convergent validity (Cronbachα = 0.962) and low discriminant validity (one extracted component), of the e-version were detected. Performing inter-group comparisons highlighted statistical differences in terms of higher education level (z = -2.436, P = 0.015) and earlier CKD stages (z = -1.978, P = 0.048), with these patients often preferring to respond. No significant differences were detected in the clinical profiles between respondents who obtained an above or below average questionnaire score. CONCLUSION: The e-version is reliable but was not shown to be a valid approach. Audiences with higher education levels and less advanced disease condition may prefer to respond to the e-version. Adaptation of this e-questionnaire, from its original paper version, may not be a direct transition and meticulous modifications may be required during the transition process. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900024633).

TRIM65 Promotes Invasion of Endometrial Stromal Cells by Activating ERK1/2/C-myc Signaling via Ubiquitination of DUSP6.

BACKGROUND: Endometriosis (EM) is a benign gynecological disease that shares some characteristics with malignancy, such as proliferation and invasion. So far, the pathogenesis of EM is still unclear. In this study, we investigated whether TRIM65 can play a role in the development of EM. METHODS: TRIM65 expression levels in eutopic, ectopic, and normal endometrium were detected by quantitative real-time PCR and Western blot. Cell proliferation and invasion of primary endometrial stromal (EMS) cells were detected by CCK-8 and Transwell analysis. The interaction between TRIM65 and DUSP6 or C-myc was measured by coimmunoprecipitation, ubiquitylation, dual luciferase, and chromatin immunoprecipitation analysis. RESULTS: We found that TRIM65 was identified as an up-regulated gene in ectopic endometrial tissues and EMS cells compared with control groups without EM. TRIM65 expression was positively correlated with the levels of p-ERK1/2, C-myc, matrix metalloproteinase-2, and integrin ß1 in ectopic endometrial tissues in patients and mice. TRIM65 promoted the cell proliferation and invasion of EMS cells via the ERK1/2/C-myc pathway through ubiquitination of DUSP6. C-myc promoted TRIM65 expression through inducing TRIM65 promoter activity. Additionally, the increased expression of TRIM65, C-myc, matrix metalloproteinase-2, integrin ß1, and p-ERK1/2 and the decreased expression of DUSP6 in ectopic endometrial tissues were significantly suppressed by inhibition of ERK1/2 signaling pathway in ectopic endometrial tissues in experimental mice model. CONCLUSION: In conclusion, TRIM65 promotes invasion of ectopic EMS cells by activating a feedback loop with the ERK1/2/C-myc signaling pathway and may be a potential therapeutic target for EM.

Refinement and Evaluation of a Chinese and Western Medication Adherence Scale for Patients with Chronic Kidney Disease: Item Response Theory Analyses.

PURPOSE: This study aimed to simplify the version-1 Chinese and Western medication adherence scale for patients with chronic kidney disease (CKD) to a version-2 scale using item response theory (IRT) analyses, and to further evaluate the performance of the version-2 scale. MATERIALS AND METHODS: Firstly, we refined the version-1 scale using IRT analyses to examine the discrimination parameter (a), difficulty parameter (b) and maximum information function peak (Imax). The final scale refinement from version-1 to version-2 scale was also decided upon clinical considerations. Secondly, we analyzed the reliability and validity of version-2 scale using classical test theory (CTT), as well as difficulty, discrimination and Imax of version-1 and version-2 scale using IRT in order to conduct scale evaluation. RESULTS: For scale refinement, the 26-item version-1 scale was reduced to a 15-item version-2 scale after IRT analyses. For scale evaluation using CTT, internal consistency reliability (total Cronbach α = 0.842) and test-rest reliability (r = 0.909) of version-2 scale were desirable. Content validity indicated 3 components of knowledge, belief and behaviors. We found meritorious construct validity with 3 detected components as the same construct of medication knowledge (items 1-9), medication behavior (items 13-15), and medication belief (items 10-12) based upon exploratory factor analysis. The correlation between the version-2 scale and Morisky, Green and Levine scale (MGL scale) was weak (Pearson coefficient = 0.349). For scale evaluation with IRT, the findings showed enhanced discrimination and decreased difficulty of most retained items (items 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15), decreased Imax of items 1, 2, 3, 4, 6, 11, 14, as well as increased Imax of items 5, 7, 8, 9, 10, 12, 13, 14, 15 in the version-2 scale than in the version-1 scale. CONCLUSION: The original Chinese and Western medication adherence scale was refined to a 15-item version-2 scale after IRT analyses. The scale evaluation using CTT and IRT showed the version-2 scale had the desirable reliability, validity, discrimination, difficulty, and information providedoverall. Therefore, the version-2 scale is clinically feasible to assess the medication adherence of CKD patients.

Mannoside-Modified Branched Gold Nanoparticles for Photothermal Therapy to MDA-MB-231 Cells.

Recently, gold nanoparticles (Au NPs) have been used to study the treatment of malignant tumors due to their higher biocompatibility and lesser toxicity. In addition, they can be excited through a specific wavelength to produce oscillating plasmonic photothermal therapy (PPTT) on the basis of the localized surface plasma resonance (LSPR) effect. Au NPs can be heated to kill cancer cells in specific parts of the body in a noninvasive manner. In this study, branched gold nanoparticles (BAu NPs) were prepared by mixing HAuCl4 in a 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solution in a molar ratio of 1:2000. The UV-vis absorption peak was detected in the range of 700-1000 nm. Subsequently, BAu NPs were chemically linked to a thiol-modified mannoside molecule via a stable sulfur-Au covalent bond (Man@BAu NPs). Due to the presence of abundant mannose receptors on human-breast-cancer cells, MDA-MB-231, Man@BAu NPs were found to be abundant inside cancer cells. After irradiating the Man@BAu NP-laden MDA-MB231 switch with a near-infrared (NIR) laser at 808 nm wavelength, the photothermal-conversion effect raised the surface temperature of Man@BAu NPs, thus inducing cell death. Our experiment results demonstrated the advantages of applying Man@BAu NPs in inducing cell death in MDA-MB-231.

A computational study of the Fenton reaction in different pH ranges.

The reaction of iron(ii) and hydrogen peroxide, namely the Fenton reaction, is well-known for its strong oxidizing capability. While the Fenton reactions are ubiquitous and have wide applications in many areas, the detailed mechanism, especially the nature of the reactive intermediates responsible for oxidation, is not completely clear. In this work, the performances of various density functional theory (DFT) methods on the relative energies of key Fenton intermediates are evaluated. The DFT method selected from the benchmark study is then exploited to investigate the aqueous Fenton reactions in different pH conditions. The results show that at pH > 2.2, the major Fenton oxidants are high-valent oxoiron(iv) aquo complexes. However, depending on the pH conditions, these complexes can exist in three protonation states that display quite different oxidation reactivities. The oxidizing power of FeIV[double bond, length as m-dash]O is found to be principally determined by the total charge of the ligands and is less influenced by the axial ligand effect. Moreover, the calculations reveal that the presence of the hydronium ion can stabilize the intermediate of the hydroxyl radical and further inhibit oxoiron(iv) formation via proton transfer. The contribution of hydroxyl radicals could compete with the oxoiron(iv) species at pH below 2.2. In addition, high-level ab initio calculations question the existence of the iron(iv)-dihydroxo intermediate suggested in the literature. The implications of the computational results for the Fenton oxidation process, cytochrome P450, and catalyst design are discussed.