External Validation of the Kidney Failure Risk Equation Among Urban Community-Based Chinese Patients With CKD.

Rationale & Objective: The Kidney Failure Risk Equations have been proven to perform well in multinational databases, whereas validation in Asian populations is lacking. This study sought to externally validate the equations in a community-based chronic kidney disease cohort in China. Study Design: A retrospective cohort study. Setting & Participants: Patients with and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 dwelling in an industrialized coastal city of China. Exposure: Age, sex, eGFR, and albuminuria were included in the 4-variable model, whereas serum calcium, phosphate, bicarbonate, and albumin levels were added to the previously noted variables in the 8-variable model. Outcome: Initiation of long-term dialysis treatment. Analytical Approach: Model discrimination, calibration, and clinical utility were evaluated by Harrell's C statistic, calibration plots, and decision curve analysis, respectively. Results: A total of 4,587 participants were enrolled for validation of the 4-variable model, whereas 1,414 were enrolled for the 8-variable model. The median times of follow-up were 4.0 (interquartile range: 2.6-6.3) years for the 4-variable model and 3.4 (2.2-5.6) years for the 8-variable model. For the 4-variable model, the C statistics were 0.750 (95% CI: 0.615-0.885) for the 2-year model and 0.766 (0.625-0.907) for the 5-year model, whereas the values were 0.756 (0.629-0.883) and 0.774 (0.641-0.907), respectively, for the 8-variable model. Calibration was acceptable for both the 4-variable and 8-variable models. Decision curve analysis for the models at the 5-year scale performed better throughout different net benefit thresholds than the eGFR-based (<30 mL/min/1.73 m2) strategy. Limitations: A large proportion of patients lack albuminuria measurements, and only a subset of population could provide complete data for the 8-variable equation. Conclusions: The kidney failure risk equations showed acceptable discrimination and calibration and better clinical utility than the eGFR-based strategy for incidence of kidney failure among community-based urban Chinese patients with chronic kidney disease.

Accurate and reliable risk evaluation of chronic kidney disease (CKD) prognosis can be helpful for physicians to make decisions concerning treatment opportunity and therapeutic strategy. The kidney failure risk equation is an outstanding model for predicting risk of kidney failure among patients with CKD. However, the equation is lacking validation among Chinese populations. In the current study, we demonstrated that the equation had good discrimination among an urban community-based cohort of patients with CKD in China. The calibration was also acceptable. Decision curve analysis also showed that the equation performed better than a traditional kidney function-based strategy. The results provide the basis for using predictions derived from the kidney failure risk equation to improve the management of patients with CKD in community settings in China.

Effects of nitrate reduction on the biotransformation of 1H-1,2,4-triazole: Mechanism and community evolution.

Due to the refractory of 1 H-1,2,4-triazole (TZ), conventional anaerobic biological treatment technology is usually restricted by low removal efficiency and poor system stability. In this study, TZ biodegradation and nitrate reduction was coupled to improve the removal efficiency of TZ from polluted wastewater. Batch assay was performed with pure culture strain Raoultella sp. NJUST42, which was reported to have the capability to degrade TZ in our previous study. Based on batch assay result, complete removal of TZ could be achieved in the presence of nitrate, whereas only 50% of TZ could be removed in the control system. Long-term stability experiment indicated that the relative abundance of microorganisms (Bacteroidetes_vadinHA17, Georgenia, Anaerolinea, etc) was obviously enhanced under nitrate reduction condition. During long-term period, major intermediates for TZ biodegradation such as [1,2,4]Triazolidine-3,5-diol, hydrazine dibasic carboxylic acid and carbamic acid were detected. A novel TZ biotransformation approach via hydration, TZ-ring cleavage, deamination and oxidation was speculated. PICRUSt1 and KEGG pathway analyses indicated that hydration (dch), oxidation (adhD, oah, pucG, fdhA) of TZ and nitrate reduction (Nar, napA, nrfA, nirBK, norB, nosZ) were significantly enhanced in the presence of nitrate. Moreover, the significant enrichment of TCA cycle (gab, sdh, fum, etc.) indicated that carbon and energy metabolism were facilitated with the addition of nitrate, thus improved TZ catabolism. The proposed mechanism demonstrated that TZ biodegradation coupled with nitrate reduction would be a promising approach for efficient treatment of wastewater contaminated by TZ.

Research trends and hotspots in the field of electrical impedance tomography for mechanical ventilation: a bibliometric analysis.

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.

Photoredox-Catalyzed Alkene Amination: C(sp2)-H/N-H Radical-Radical Cross Dehydrogenative Coupling.

Direct alkene C-H/N-H cross dehydrogenative coupling is an infrequent, highly challenging transformation. Herein, a photoredox radical-radical cross-coupling reaction between ketene dithioacetal as a persistent alkene radical cation and azole nitrogen center radical (NCR) was developed. This direct alkene amination proceeded through a synergistic photoredox and cobalt catalysis, with only H2 evolution. The reaction showed excellent tolerance and highly regio- and stereospecific manner, expanding the scope of C(sp2)-N construction methods and radical cross-coupling modes.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

Daratumumab-based immunotherapy vs. lenalidomide, bortezomib and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: a systemic review.

Background: Since no randomized controlled trials have directly compared the efficacy and safety of immunotherapy with daratumumab versus lenalidomide/bortezomib/dexamethasone (RVD) in the frontline treatment of transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM), this study systematically reviewed the clinical studies regarding immunotherapy with daratumumab and RVD regimen in the treatment of TIE-NDMM to explore the optimization direction of the best first-line therapy. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to collect studies on regimens containing daratumumab or RVD/RVD-lite for TIE-NDMM. Pooled and meta-analysis was then performed to compare the overall response rate (ORR), stringent complete remission (sCR) and CR rate, progression-free survival (PFS), overall survival (OS) and treatment-related discontinuation rate between daratumumab-containing immunotherapy regimen and RVD/RVD-lite regimen by using R 4.3.1 software. Results: Nine prospective clinical trials were included, including 1795 TIE-NDMM or NDMM without intent for immediate ASCT. Among them, 938 patients were treated with daratumumab-based immunotherapy and 857 with RVD/RVD-lite regimens. Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01). The median PFS of the daratumumab-based and RVD/RVD-lite groups were 52.6 months and 35.1 months respectively (HR 0.77, 95%CI, 0.66-0.90). The median OS of both groups was not reached, and there were no significant differences in OS between the two groups (HR 1.03, 95%CI, 0.86-1.23). The therapy discontinuation rate led by adverse events was significantly higher in the RVD/RVD-lite group than in the daratumumab-based regimen group for the TIE-NDMM (16% vs. 7%, P=0.03). Conclusion: This meta-analysis suggests that daratumumab-containing immunotherapy is superior to RVD in the depth of treatment efficacy, progression-free survival, and lower treatment-related discontinuation rates. Limited by the lack of head-to-head clinical trials, this conclusion needs to be verified by concurrent cohort studies.

Establishment and validation of a nomogram to predict postoperative anemia after total hip arthroplasty.

BACKGROUND: Anemia is a common complication of total hip arthroplasty (THA). In this study, we evaluated the preoperative risk factors for postoperative anemia after THA and developed a nomogram model based on related preoperative and intraoperative factors. METHODS: From January 2020 to May 2023, 927 THA patients at the same medical center were randomly assigned to either the training or validation cohort. The correlation between preoperative and intraoperative risk factors and postoperative anemia after THA was evaluated using univariate and multivariate logistic regression analysis. A nomogram was developed using these predictive variables. The effectiveness and validation for the clinical application of this nomogram were evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: Through univariate and multivariate logistic regression analysis, 7 independent predictive factors were identified in the training cohort: Lower body mass index (BMI), extended operation time, greater intraoperative bleeding, lower preoperative hemoglobin level, abnormally high preoperative serum amyloid A (SAA) level, history of cerebrovascular disease, and history of osteoporosis. The C-index of the model was 0.871, while the AUC indices for the training and validation cohorts were 84.4% and 87.1%, respectively. In addition, the calibration curves of both cohorts showed excellent consistency between the observed and predicted probabilities. The DCA curves of the training and validation cohorts were high, indicating the high clinical applicability of the model. CONCLUSIONS: Lower BMI, extended operation time, increased intraoperative bleeding, reduced preoperative hemoglobin level, elevated preoperative SAA level, history of cerebrovascular disease, and history of osteoporosis were seven independent preoperative risk factors associated with postoperative anemia after THA. The nomogram developed could aid in predicting postoperative anemia, facilitating advanced preparation, and enhancing blood management. Furthermore, the nomogram could assist clinicians in identifying patients most at risk for postoperative anemia.

Nanocrystals Incorporated with Mordenite Zeolite Composites with Enhanced Upconversion Emission for Cu2+ Detection.

In this research, upconversion nanocrystals incorporated with MOR zeolite composites were synthesized using the desilicated MOR zeolite as a host for the in situ growth of NaREF4 (RE = Y, Gd) Yb/Er nanocrystals. The structure and morphology of the composites were studied with XRD, XPS, and TEM measurements, and the spectral studies indicated that the subsequent thermal treatment can effectively improve the upconversion emission intensity of Er3+. By using the NaYF4:Yb/Er@DSi1.0MOR-HT composite that holds the strongest upconversion emission, a probe of UCNC@DSiMOR/BPEI was constructed with the modification of branched poly ethylenimine for the detection of Cu2+. It was indicated that the integrated emission intensity of Er3+ shows a linear dependence with the logarithm value of the Cu2+ concentration ranging from 0.1 to 10 µM. This study offered a feasible method for the construction of UCNC@zeolite composites with enhanced upconversion emission, which may have a potential application as fluorescent probes for the detection of various metal ions by adjusting the doping luminescent center.

Machine learning-based prediction of in-hospital mortality for critically ill patients with sepsis-associated acute kidney injury.

OBJECTIVES: This study aims to develop and validate a prediction model in-hospital mortality in critically ill patients with sepsis-associated acute kidney injury (SA-AKI) based on machine learning algorithms. METHODS: Patients who met the criteria for inclusion were identified in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and divided according to the validation (n = 2440) and development (n = 9756, 80%) queues. Ensemble stepwise feature selection method was used to screen for effective features. The prediction models of short-term mortality were developed by seven machine learning algorithms. Ten-fold cross-validation was used to verify the performance of the algorithm in the development queue. The area under the receiver operating characteristic curve (ROC-AUC) was used to evaluate the differentiation accuracy and performance of the prediction model in the validation queue. The best-performing model was interpreted by Shapley additive explanations (SHAP). RESULTS: A total of 12,196 patients were enrolled in this study. Eleven variables were finally chosen to develop the prediction model. The AUC of the random forest (RF) model was the highest value both in the Ten-fold cross-validation and evaluation (AUC: 0.798, 95% CI: 0.774-0.821). According to the SHAP plots, old age, low Glasgow Coma Scale (GCS) score, high AKI stage, reduced urine output, high Simplified Acute Physiology Score (SAPS II), high respiratory rate, low temperature, low absolute lymphocyte count, high creatinine level, dysnatremia, and low body mass index (BMI) increased the risk of poor prognosis. CONCLUSIONS: The RF model developed in this study is a good predictor of in-hospital mortality for patients with SA-AKI in the intensive care unit (ICU), which may have potential applications in mortality prediction.

Acupoint transplantation versus non-acupoint transplantation using autologous peripheral blood mononuclear cells in treating peripheral arterial disease.

Numerous studies have discussed the therapeutic outcomes of using cell therapy or acupuncture to treat peripheral artery disease (PAD). However, there are no long-term studies on the safety and efficacy of transplanting peripheral blood mononuclear cells (PBMNCs) via acupoints to treat PAD. We first reviewed the short-term and long-term clinical results of PAD patients treated with PBMNCs through intramuscular non-acupoint transplantation (control group; n = 45) or intramuscular acupoint transplantation (acupoint group; n = 45) at a single university hospital general medical center between December 2002 and September 2022. Pain intensity (assessed with the verbal rating scale [VRS] score) in the acupoint group was considerably lower than that in the control group at month 1 (mean ± standard deviation [SD]: 1.29 ± 0.96 vs 1.76 ± 0.82; P = 0.016) and month 3 (mean ± SD: 1.27 ± 0.90 vs 1.61 ± 0.86; P = 0.042). We observed significant improvement of VRS score (P < .001 for all) and ankle-brachial index (ABI; P < .001 for all) from baseline in both groups at months 1, 3, 6, 12, 36, and 60. The 10-year cumulative rate of major amputation-free survival (MAFS) was higher in the acupoint group as compared to the control group (81.9%, 95% confidence interval [CI]: 71.3%-94.1% vs 78.5%, 95% CI: 66.7%-92.3%; P = 0.768). Compared with the routine injection method, intramuscular transplantation of PBMNCs via selected acupoints could significantly decrease the short-term pain intensity in patients with PAD, which remains an option for consideration.

Comparison of Dentatorubrothalamic Tractography Methods Based on the Anatomy of the Rubral Wing.

BACKGROUND AND OBJECTIVES: Precise localization of the dentatorubrothalamic (DRT) tract can facilitate anatomic targeting in MRI-guided high-intensity focused ultrasound (HIFU) thalamotomy and thalamic deep brain stimulation for tremor. The anatomic segment of DRT fibers adjacent to the ventral intermediate nucleus of the thalamus (VIM), referred to as the rubral wing (RW), may be directly visualized on the fast gray matter acquisition T1 inversion recovery. We compared reproducibility, lesion overlap, and clinical outcomes when reconstructing the DRT tract using a novel anatomically defined RW region of interest, DRT-RW, to an existing tractography method based on the posterior subthalamic area region of interest (DRT-PSA). METHODS: We reviewed data of 23 patients with either essential tremor (n = 18) or tremor-predominant Parkinson's disease (n = 5) who underwent HIFU thalamotomy, targeting the VIM. DRT tractography, ipsilateral to the lesion, was created based on either DRT-PSA or DRT-RW. Volume sections of each tract were created and dice similarity coefficients were used to measure spatial overlap between the 2 tractographies. Post-HIFU lesion size and location (on postoperative T2 MRI) was correlated with tremor outcomes and side effects for both DRT tractography methods and the RW itself. RESULTS: DRT-PSA passed through the RW and DRT-RW intersected with the ROIs of the DRT-PSA in all 23 cases. A higher percentage of the RW was ablated in patients who achieved tremor control (18.9%, 95% CI 15.1, 22.7) vs those without tremor relief (6.7%, 95% CI% 0, 22.4, P = .017). In patients with tremor control 6 months postoperatively (n = 12), those with side effects (n = 6) had larger percentages of their tracts ablated in comparison with those without side effects in both DRT-PSA (44.8, 95% CI 31.8, 57.8 vs 24.2%, 95% CI 12.4, 36.1, P = .025) and DRT-RW (35.4%, 95% CI 21.5, 49.3 vs 21.7%, 95% CI 12.7, 30.8, P = .030). CONCLUSION: Tractography of the DRT could be reconstructed by direct anatomic visualization of the RW on fast gray matter acquisition T1 inversion recovery-MRI. Anatomic planning is expected to be quicker, more reproducible, and less operator-dependent.

Tannic acid adsorption properties of cellulose nanocrystalline/fish swim bladder gelatin composite sponge.

Foods and beverages with excessive tannins acid (TA) content taste astringent and bitter. The overconsumption of TA could result in nutritional and digestive problems. In this study, the cellulose nanocrystals (CNC)/fish swim bladder gelatin (FG) composite sponge was prepared with glutaraldehyde as a crosslinking agent. The TA adsorption performance of the sponge was discussed. The freeze-dried CNC/FG composite sponge had a porous network structure. CNC was combined into the FG matrix as a reinforcing phase. The mechanical strength, thermal stability, and swelling properties of the composite sponge were improved with the addition of an appropriate amount of CNC. Although CNC decreased the porosity of composite sponge, the increase in active adsorption sites resulted in an overall positive effect on its TA adsorption properties. Under the optimal adsorption conditions, the TA removal rate of 1.0 % CNC composites reached 80.4 %. Furthermore, the sponge retained a TA removal rate of 54 % after five cycles of adsorption and desorption using 50 % ethanol. The results demonstrated that CNC/FG composite sponge has application potential in the field of adsorption materials for TA.

Implications on growth performance, glucose metabolism, PI3K/AKT pathway, intestinal flora induced by dietary taurine in a high-carbohydrate diet for grass carp (Ctenopharyngodon idella).

An 8-week experiment was performed to investigate the influence on growth performance, plasma biochemistry, glucose metabolism and the insulin pathway of supplementation of dietary taurine to a high-carbohydrate diet for grass carp. In this study, fish were fed diets at one of two carbohydrate levels, 31·49 % (positive control) or 38·61 % (T00). The high-carbohydrate basal diet (T00), without taurine, was supplemented with 0·05 % (T05), 0·10 % (T10), 0·15 % (T15) or 0·20 % (T20) taurine, resulting in six isonitrogenous (30·37 %) and isolipidic (2·37 %) experimental diets. The experimental results showed that optimal taurine level improved significantly weight gain, specific growth rate (SGR), feed utilisation, reduced plasma total cholesterol levels, TAG and promoted insulin-like growth factor level. Glucokinase, pyruvate kinase and phosphoenolpyruvate carboxykinase activities showed a quadratic function model with increasing dietary taurine level, while hexokinase, fatty acid synthetase activities exhibited a positive linear trend. Optimal taurine supplementation in high-carbohydrate diet upregulated insulin receptor (Ir), insulin receptor substrate (Irs1), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt1), glycogen synthase kinase 3 ß (gs3kß) mRNA level and downregulated insulin-like growth factor (igf-1), insulin-like growth factor 1 receptor (igf-1R) and Fork head transcription factor 1 (foxo1) mRNA level. The above results suggested that optimal taurine level could improve growth performance, hepatic capacity for glycolipid metabolism and insulin sensitivity, thus enhancing the utilisation of carbohydrates in grass carp. Based on SGR, dietary optimal tributyrin taurine supplementation in grass carp was estimated to be 0·08 %.

Early clinical efficacy analysis of enhanced recovery following surgery combined with interscalene brachial plexus block for arthroscopic rotator cuff repair.

To explore the early clinical value of enhanced recovery after surgery (ERAS) with interscalene brachial plexus block (ISB) for arthroscopic rotator cuff repair (ARCR). We enrolled 240 patients who underwent arthroscopic rotator cuff repair, randomly divided into 3 groups (n = 80 each). Groups A, B, and C underwent only surgery, surgery + ERAS, and ISB + surgery + ERAS, respectively. We analyzed the clinical data and postoperative indicators for the 3 patient groups. Group comparisons of clinical data and postoperative indicators revealed no significant differences in clinical characteristics (P > .05). Group C showed superior Visual Analog Scale scores at 0-6 and 6-24 hours postoperatively (P < .05), and the shortest length of hospital stay (LOS) (P < .05). At 6 weeks and 3 months postoperatively, Constant-Murley shoulder score and University of California-Los Angeles scores were better in Groups B and C than in Group A (P < .05). Joint swelling was more common in Group A than in Groups B and C (P < .05) but with no significant difference in the incidence of postoperative stiffness (P > .05). ERAS can relieve postoperative pain, shorten LOS, and help restore shoulder joint mobility, thereby reducing postoperative swelling. ISB + ERAS optimized pain control and allowed a shorter LOS, but had similar effects on early functional recovery and complications.

Ginkgo biloba Extract 50 (GBE50) Exerts Antifibrotic and Antioxidant Effects on Pulmonary Fibrosis in Mice by Regulating Nrf2 and TGF-ß1/Smad Pathways.

BACKGROUND: Pulmonary fibrosis (PF) is a progressive lung disorder with a poor prognosis. GBE50 is a new standardized Ginkgo biloba extract that has been widely used in cardiovascular diseases. However, the protective mechanism of GBE50 against PF remains to be elucidated. METHODS: C57BL/6J mice were treated with bleomycin (Bleo) to induce PF in the presence or absence of GBE50. Protein content in bronchoalveolar lavage fluid (BALF) and wet weight/dry weight ratio were examined for analysis of pulmonary edema. Hematoxylin-eosin staining and Masson trichrome staining were used for histopathological observation of murine lung tissues. Ashcroft score was used for semi-quantitation of lung fibrosis degree. RT-qPCR was utilized for assessing mRNA levels of pro-fibrotic mediators in lung tissues. TUNEL staining was implemented for cell apoptosis assessment. The levels of oxidative stress- and inflammation-related markers were evaluated by corresponding commercial assay kits. Western blotting was used to evaluate levels of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling- and transforming growth factor (TGF)-ß1/SMAD signaling-related proteins. RESULTS: GBE50 alleviated lung injury and severity of fibrosis, reduced collagen deposition and cell apoptosis in lung tissues, and suppressed inflammatory response and oxidative stress injury in Bleo-stimulated PF mice. GBE50 activated Nrf2 signaling pathway and inactivated TGF-ß1/SMAD signaling pathway in the lungs of Bleo-induced PF mice. Inhibition of Nrf2 signaling reversed GBE50-mediated inactivation of TGF-ß1/SMAD signaling and attenuation of inflammation and oxidative stress in Bleo-induced PF mice. CONCLUSION: GBE50 protects against Bleo-induced PF in mice by mitigating fibrosis, inflammation and oxidative stress via Nrf2 and TGF-ß1/SMAD signaling pathways.

Correlation between bone mineral density and bone metabolic markers in postmenopausal women with osteoporotic fractures at different C-terminal telopeptide of type 1 collagen levels: a retrospective analysis study.

OBJECTIVE: This study aimed to analyze the correlation between bone mineral density (BMD) and bone resorption markers in postmenopausal women with osteoporosis fractures and identify risk factors for second fractures. METHODS: This retrospective analysis of 1,239 older women with fractures with a median age of 70 years who attended Shanghai General Hospital from January 2007 to December 2016, included a first fracture group (1,008 cases) and a second fractures group (231 cases). The risk factors for fractures were analyzed by comparing these groups on clinical characteristics, BMD, and bone metabolism markers stratified by quartiles of serum C-terminal telopeptide of type 1 collagen (CTX). Binary logistic regression analysis was used to identify risk factors for second fractures. RESULTS: In the whole sample, BMD was negatively correlated with age and serum osteocalcin and positively correlated with body mass index (BMI). In women with first fractures, those in the highest quartile of serum CTX had the lowest spine and hip BMD. Second fractures were significantly associated with BMI, lower spine and hip BMD, and higher serum osteocalcin but not CTX. Binary logistic regression analysis showed that high BMI (odds ratio [OR], 1.08 [95% CI, 1.03-1.14]; P = 0.001), low lumbar BMD (OR, 0.24 [95% CI, 0.07-0.82]; P = 0.023), low total hip BMD (OR, 0.05 [95% CI, 0.00-0.88]; P = 0.041), and lack of antiosteoporosis treatment (OR, 2.71 [95% CI, 2.71-4.08]; P < 0.001) were independent risk factors for second fractures. CONCLUSIONS: In older women with fractures, BMD was significantly lower in women with second fractures than in those with first fractures. Higher levels of serum CTX and osteocalcin, which indicates increased bone resorption, were negatively correlated with BMD. In women with a first fracture, serum CTX higher than 605 pg/mL was negatively correlated with BMD, whereas no correlation was found between different CTX and BMD in women with second fractures. High BMI and low BMD as well as not receiving antiosteoporosis treatment were independent risk factors for second fractures.

Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions.

BACKGROUND: The aim of this study was to determine the prevalence of high-risk human papillomavirus (HR-HPV) and the correlation between multiple infections and cervical lesions. METHODS: The current study involved population-based sample of 20,059 women who underwent cervical screening for 15 HR-HPV genotypes with ThinPrep cytologic test (TCT) results. The correlation between multiple HPV genotype infections and cervical lesions was also determined. The odds ratios (ORs) were calculated to assess co-infection patterns for each genotype with 15 other genotypes and the additive statistical interactions were evaluated. RESULTS: There was a bimodal pattern among multiple HPV infections, with a peak in the younger group and a second peak in the elderly group. Indeed, most multiple HPV genotypes exhibited a bimodal pattern. The most common HPV type in patients with high-grade squamous intraepithelial lesions (HSILs) was HPV-16, followed by HPV-52, HPV-58, and HPV-33. The most frequent HPV type in patients with cervical cancer was HPV-16, followed by HPV-58 and HPV-33. Women with multiple infections were at a increased risk of low-grade squamous intraepithelial lesions [LSIL] (OR = 2.01; 95% CI 1.38-2.93) and HSIL (OR 2.28; 95% CI 1.36-3.81) when compared to women with single infections. patients with cervical cancer had the higher percentage of multiple HPV infections. Based on the data herein, we suggest that HPV-33 and HPV-58 may also be high-risk HPV types worthy of increased surveillance and follow-up. CONCLUSION: Our findings suggested that the association between multiple HPV infections and HSIL and LSIL are stronger compared to single HPV infections. There may be some specific combinations that synergistically affected the risk of HSIL and LSIL.

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

Study on the Sliding Tribological Behavior of Oleic Acid-Modified MoS2 under Boundary Lubrication.

The effects of MoS2 and MoS2 modified by adding oleic acid (OA) on the friction properties of lithium-based grease under boundary lubrication conditions are studied by molecular dynamics (MD) simulation and experiment. A rough wall boundary lubrication MD model with peaks and grooves is established to simulate the mechanical properties and lubrication effects of three lubrication systems on rough walls for the relative shear velocity between the two solid walls of 5 m/s at 500 MPa. The stress, wear amount, friction force, normal pressure, and friction heat of the friction surface are quantitively calculated. Simultaneously, a Retc friction and wear testing machine is used to measure the friction coefficient under different concentrations of additives and different pressures. The results show that the grease added with MoS2 can reduce friction, wear, and the temperature between friction pairs. However, under high pressure and shear, MoS2 can easily agglomerate and accumulate in the pits, reducing the lubricating effect. At the same time, since OA-modified MoS2 can reduce agglomeration, the modified MoS2 is adsorbed on the metal wall surface, forming a stable lubricant film. The main contributions of this article can be found in combining MD simulation and experimentation, establishing the connection between micronano structures and macroscopic properties, exploring the mechanism of the influence of wall roughness and particle size on the friction performance of lubricating oil, and providing a theory for predicting and developing high-performance new lubricating grease.