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OBJECTIVE: Active vitamin D analogs and calcimimetic agents are primary drugs for patients with secondary hyperparathyroidism. Due to the different pharmacological mechanisms, they have different effects on the level of parathyroid hormone, serum calcium, phosphorus, and bone turnover biomarkers. This study aimed to evaluate the active vitamin D analogs and calcimimetic agents in hemodialysis patients with secondary hyperparathyroidism. METHODS: We included randomized clinical trials of hemodialysis patients with secondary hyperparathyroidism, comparing active vitamin D analogs to calcimimetic agents or placebo/control. The primary outcome was the change of PTH level from baseline to end-up. The secondary outcome was the change in serum calcium, phosphorus, calcium-phosphorus product, and bone turnover biomarkers. A network meta-analysis method was applied to complete this study. The forest plots reflected statistical differences in the outcomes between active vitamin D analogs and calcimimetic agents. The SUCRA result presented the ranking of impact on the outcomes. RESULTS: Twenty-one randomized clinical trials with 4653 patients were included in this network meta-analysis. Global and splitting-node inconsistencies provided no evidence of inconsistency in this study. There was no statistical difference between two active vitamin D analogs and three calcimimetic agents in the PTH, and phosphorus levels changed. Considering serum calcium level, compared with placebo, calcitriol (9.73, 3.09 to 16.38) and paricalcitol (9.74, 3.87 to 15.60) increase serum calcium. However, cinacalcet (- 1.94, - 3.72 to - 0.15) and etelcalcetide (- 7.80, - 11.80 to - 3.80) reduced the serum calcium, even a joint use of cinacalcet with active vitamin D analogs (- 5.83, - 9.73 to - 1.93). Three calcimimetic agents decreased calcium levels much more than calcitriol and paricalcitol. The same type of drugs was not distinct, with each one affecting the change in calcium level. Cinacalcet reduced calcium-phosphorus product much more than paricalcitol (- 3.66, - 6.72 to - 0.60). Evocalcet decreased calcium-phosphorus product more than cinacalcet (- 5.64, - 8.91 to - 2.37), calcitriol (- 9.36, - 14.81 to - 3.92), and paricalcitol (- 9.30, - 13.78 to - 4.82). Compared with paricalcitol, cinacalcet significantly increases the level of ALP (24.50, 23.05 to 25.95) and bALP (0.67, 0.03 to 1.31). The incidence of gastrointestinal disorders in cinacacet (29.35, 1.71 to 504.98) and etelcalcetide (20.92, 1.20 to 365.68) was notably higher than in paricalcitol. Etelcalcetide (0.71, 0.53 to 0.96) and evocalcet (0.46, 0.33 to 0.64) presented a lower rate of gastrointestinal disorders than cinacalcet. Cinacalcet ranked first in adverse gastrointestinal, nervous, and respiratory reactions. CONCLUSION: The same kinds of agents perform similar efficacy on the level of PTH, serum calcium, phosphorus, and calcium-phosphorus product. Paricalcitol did not lead to more hypercalcemia than calcitriol. The calcium decrease induced by cinacalcet was not settled even by associating it with active vitamin D analogs. Cinacalcet and evocalcet were superior to calcitriol and paricacitol in reducing calcium-phosphorus product. Calcimimetics induced more gastrointestinal disorders than active vitamin D analogs, especially cinacalcet.
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Defect manipulation in metal oxide is of great importance in boosting catalytic performance for propane oxidation. Herein, a selective atom removal strategy was developed to construct a defective manganese oxide catalyst, which involved the partial etching of a Mg dopant in MnOx. The resulting MgMnOx-H catalysts exhibited superior low-temperature catalytic activity (T50 = 185 °C, T90 = 226 °C) with a propane conversion rate of 0.29 µmol·gcat.-1·h-1 for the propane oxidation reaction, which is 4.8 times that of pristine MnOx. Meanwhile, a robust hydrothermal stability was guaranteed at 250 °C for 30 h of reaction time. The comprehensive experimental characterizations revealed that the catalytic performance improvement was closely related to the defective structures including the abundant (metal and oxygen) vacancies, distorted crystals, valence imbalance, etc., which prominently weakened the Mn-O bond and stimulated the mobility of surface lattice oxygen, leading to the elevation in the intrinsic oxidation activity. This work exemplifies the significance of defect engineering for the promotion of the oxidation ability of metal oxide, which will be valuable for the further development of efficient non-noble metal catalysts for propane oxidation.
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INTRODUCTION: Limited real-world evidence exists about the burden of atopic dermatitis (AD) in patients receiving systemic or non-systemic therapies in clinical practices. ESSENTIAL AD was an observational study that aimed to fill this information gap. METHODS: ESSENTIAL AD enrolled (September 2021-June 2022) adult patients with physician-confirmed AD that was routinely managed with systemic and non-systemic treatment in a real-world setting from 15 countries in Eastern Europe, the Middle East, and Africa. Primary outcome variables were Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI) assessed during one office visit. RESULTS: A total of 799 enrolled patients fulfilled selection criteria and were included in the study. Patients mean (standard deviation [SD]) age was 36.3 (14.4) years, 457 (57.2%) were female, and the majority of patients were white (647 [81.0%]). Mean (SD) time since AD diagnosis was 17.6 (15.2) years (median 16.5; interquartile range [IQR] 3.3-26.8). The mean (SD) EASI, SCORAD, and DLQI total scores were 11.3 (11.3 [median 8.1; IQR 3.6-15.8]), 37.8 (17.9 [median 35.5; IQR 24.2-49.0]), and 10.6 (7.2 [median 10.0; IQR 5.0-15.0]), respectively. Patients receiving systemic treatment had significantly higher disease burden (mean [SD] EASI 13.3 [13.0]; median [IQR] 9.6 [3.9-17.9]) versus non-systemic treatment (mean [SD] 9.3 [8.7]; median [IQR] 6.8 [3.0-13.2]; P < 0.0001). Results were similar for SCORAD (39.9 [19.6] vs 35.6 [15.7]; median [IQR] 38.6 [24.7-53.1] vs 32.6 [23.9-44.6]; P = 0.0017), and DLQI total scores (11.4 [7.4] vs 9.9 [6.9]; median [IQR] 11.0 [5.0-16.0] vs 9.0 [5.0-14.0]; P = 0.0033, respectively). CONCLUSION: Patients with AD continue to have substantial disease burden despite treatment with systemic therapy, suggesting that a need for effective disease management remains, including effective therapies that improve psychological outcomes and reduce economic burden of AD, in Eastern Europe, the Middle East, and Africa.
Patients with atopic dermatitis often suffer from debilitating symptoms that impact their everyday lives. Although several treatment options are available, many patients continue to experience symptoms of disease. The ESSENTIAL AD study assessed burden of atopic dermatitis in patients receiving systemic and/or non-systemic therapies in real-life clinical practices across 15 countries in Eastern Europe, the Middle East, and Africa. The results of the study demonstrated that adult patients with atopic dermatitis continue to have substantial disease burden regardless of treatment with systemic therapy or non-systemic therapy. The findings suggest that optimal management of atopic dermatitis needs to be reassessed in Eastern Europe, the Middle East, and Africa, especially as new, more effective treatment options become available to patients.
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INTRODUCTION: Vitiligo, a chronic autoimmune skin depigmentation disease with an unpredictable course, has been associated with several comorbid autoimmune and psychological conditions. Our current understanding of vitiligo burden and management in the real world is limited. This real-world analysis presents data on vitiligo epidemiology, comorbidities, and treatment of patients in Israel. METHODS: This retrospective study analyzed data from the Maccabi Health Services database. Prevalent patients with vitiligo in 2021 were matched to patients in the general population on the basis of age group, gender, and socioeconomic status. Patient demographics, vitiligo incidence and prevalence, comorbidities, and treatment patterns are reported. Data are presented as percentages, mean, median, P values, and standard mean differences (SMD). RESULTS: In this analysis, 11,412 patients with vitiligo were matched to patients from the general population. Incidence and prevalence rates increased over time from 2005 to 2021. Compared to the general population, patients with vitiligo were more likely to have an immune-mediated comorbidity (29.7% vs 18.4% [P < 0.001; SMD 0.27]) or psychological comorbidity (18.7% vs 15.9% [P < 0.001; SMD 0.07]). Comorbidities included atopic dermatitis (patients with vitiligo vs general population 12.5% vs 8.4%), psoriasis (5.8% vs 3.6%), Hashimoto's thyroiditis (2.9% vs 1.1%), alopecia areata (2.2% vs 0.9%), depression (10.8% vs 9.5%), and sleep disorder/insomnia (5.9% vs 4.4%). Only 74.8% of all patients with vitiligo had ever received treatment, with topical corticosteroids (51.5%) and calcineurin inhibitors (36.5%) most commonly prescribed. At the end of 2021, 83.7% of patients were untreated. CONCLUSION: Patients with vitiligo are more likely to have various immune-related and psychological comorbidities, highlighting the significant impact of the condition on well-being. Nearly a quarter of patients had never received treatment, with many receiving only topical treatments, and medication persistence was low. This highlights the lack of adequate treatment in this population and the need for more effective management options.
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Comorbidity , Vitiligo , Humans , Vitiligo/epidemiology , Vitiligo/therapy , Vitiligo/psychology , Male , Female , Retrospective Studies , Adult , Israel/epidemiology , Middle Aged , Prevalence , Incidence , Young Adult , Adolescent , Child , Aged , Child, PreschoolABSTRACT
BACKGROUND: The RESCUE BT2 trial recently showcased the efficacy of tirofiban in treating acute ischemic stroke (AIS) without large or medium-sized vessel occlusion. To further assess the value of tirofiban from the perspectives of Chinese and US healthcare system, a study was conducted to evaluate its cost-effectiveness. METHODS: A hybrid model, integrating a short-term decision tree with a long-term Markov model, was developed to assess cost-effectiveness between tirofiban and aspirin for stroke patients without large or medium-sized vessel occlusion. Efficacy data for tirofiban was sourced from the RESCUE BT2 trial, while cost information was derived from published papers. Outcomes measured included respective cost, effectiveness, and incremental cost-effectiveness ratio (ICER). We conducted a one-way sensitivity analysis to assess the robustness of the results. Additionally, we performed probabilistic sensitivity analysis (PSA) through 10,000 Monte Carlo simulations to evaluate the uncertainties associated with the results. RESULTS: The study revealed that tirofiban treatment in AIS patients without large or medium-sized vessel occlusion led to a considerable reduction of 2141 Chinese Yuan (CNY) in total cost, along with a lifetime gain of 0.14 quality-adjusted life years (QALYs). In the US settings, tirofiban also exhibited a lower cost ($197,055 versus $201,984) and higher effectiveness (4.15 QALYs versus 4.06 QALYs) compared to aspirin. One-way sensitivity analysis revealed that post-stroke care costs and stroke utility had the greatest impact on ICER fluctuation in both Chinese and US settings. However, these variations did not exceed the willingness-to-pay threshold. PSA demonstrated tirofiban's superior acceptability over aspirin in over 95% of potential scenarios. CONCLUSION: Tirofiban treatment for AIS without large or medium-sized vessel occlusion appeared dominant compared to aspirin in both China and the US.
Subject(s)
Ischemic Stroke , Stroke , Humans , Ischemic Stroke/drug therapy , Tirofiban/therapeutic use , Cost-Benefit Analysis , Stroke/drug therapy , Aspirin/therapeutic use , Quality-Adjusted Life YearsABSTRACT
Objective: This study aimed to investigate the efficacy and economic effect of endovascular treatment (EVT) combined with standard medical treatment (SMT) vs. SMT alone in Chinese patients with basilar artery occlusion (BAO) from the perspective of the Chinese healthcare system. Methods: We conducted a cost-effectiveness analysis using the results from a meta-analysis comparing EVT and SMT efficacy in Chinese patients with BAO-induced stroke using direct medical costs from the China National Stroke Registry. The meta-analysis's primary outcome was excellent functional outcome (mRS scores of 0-2), with secondary outcomes being poor functional outcome (mRS scores of 3-5) and death (mRS score of 6). To compare EVT plus SMT's cost-effectiveness with that of SMT alone, we constructed a combined decision tree and Markov model with a lifetime duration and a 3-month cycle length. The primary cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER), representing the incremental cost per incremental quality-adjusted life year (QALY). EVT was considered cost-effective if the ICER was lower than the willingness-to-pay (WTP) threshold of three times the per capita gross domestic product (GDP) in 2021 in China; otherwise, it would not be cost-effective. Results: The meta-analysis results indicated that EVT could increase the incidence of excellent functional outcomes, with a risk ratio (RR) of 2.23 (95% confidence interval, CI, 1.18-4.21), p = 0.01. Simultaneously, EVT reduced the risk of poor functional outcome and mortality in the EVT group, with RRs of 0.83 (95% CI, 0.67-1.03), p = 0.09, and 0.71 (95% CI, 0.59-0.85), p = 0.0002, respectively. The study also found that EVT plus SMT resulted in a lifetime effectiveness of 2.15 QALY (3.88 life years) for 32,213 international dollars (Intl.$) per patient with BAO. In contrast, SMT alone achieved an effectiveness of 1.46 QALY (3.03 life years) with a total cost of Intl.$ 13,592 per patient. The ICER was Intl.$ 27,265 per QALY (Intl.$ 22,098 per life-year), which fell below the WTP threshold. Conclusion: Compared to SMT, EVT improves the prognosis of BAO-induced stroke. Considering the Chinese healthcare system, adding EVT to SMT proves to be cost-effective for patients with BAO compared to SMT alone.
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Porous carbon nitride/bismuth oxychloride (PCN/BiOCl-x) polymer-based heterojunction photocatalysts were successfully synthesized via a simple in situ hydrothermal method. A PCN/BiOCl heterojunction with rich chlorine defects is prepared by adjusting the chlorine content of the BiOCl unit in the heterojunction by changing the solvent. The as-prepared catalysts were characterized via BET, SEM, TEM, XRD, XPS and optical testing, and they were used for a photocatalytic amine oxidation reaction. The results indicated that the catalytic performance of the PCN/BiOCl heterojunction was significantly enhanced due to the rich chlorine vacancies in the samples. The enhanced catalytic activity may be attributed to the Z-scheme heterojunction, abundant chlorine defects and large specific surface area. At the same time, the catalyst circulation experiment shows that the PCN/BiOCl heterojunction has good circulation performance.
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Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are hypothesized to reduce the risk of anthracycline-associated cardiotoxicity. Objectives: This study sought to determine the association between SGLT2is and cardiovascular disease (CVD) after anthracycline-containing chemotherapy. Methods: Using administrative data sets, we conducted a population-based cohort study of people >65 years of age with treated diabetes and no prior heart failure (HF) who received anthracyclines between January 1, 2016, and December 31, 2019. After estimating propensity scores for SGLT2i use, the average treatment effects for the treated weights were used to reduce baseline differences between SGLT2i-exposed and -unexposed controls. The outcomes were hospitalization for HF, incident HF diagnoses (in- or out-of-hospital), and documentation of any CVD in future hospitalizations. Death was treated as a competing risk. Cause-specific HRs for each outcome were determined for SGLT2i-treated people relative to unexposed controls. Results: We studied 933 patients (median age 71.0 years, 62.2% female), 99 of whom were SGLT2i treated. During a median follow-up of 1.6 years, there were 31 hospitalizations for HF (0 in the SGLT2i group), 93 new HF diagnoses, and 74 hospitalizations with documented CVD. Relative to controls, SGLT2i exposure was associated with HR of 0 for HF hospitalization (P < 0.001) but no significant difference in incident HF diagnosis (HR: 0.55; 95% CI: 0.23-1.31; P = 0.18) or CVD diagnosis (HR: 0.39; 95% CI: 0.12-1.28; P = 0.12). There was no significant difference in mortality (HR: 0.63; 95% CI: 0.36-1.11; P = 0.11). Conclusions: SGLT2is may reduce the rate of HF hospitalization after anthracycline-containing chemotherapy. This hypothesis warrants further testing in randomized controlled trials.
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OBJECTIVE: Mesenchymal stem cell (MSC)-derived exosomes (MSC-exo) can treat reproductive disorders. However, the action of microRNAs (miRNAs) in this mechanism has yet to be systematically investigated. This study aimed to explore the effect of MSC-exo on TGF-ß1-induced endometrial fibrosis in intrauterine adhesions and elucidate the regulatory mechanisms involved in key genes by comparing miRNA expression profiles. METHODS: MSC-exo were isolated and identified based on particle size and protein marker detection. Cell counting kit-8, flow cytometry, and western blotting were used to determine the effects of MSC-exo on cell function and fibrosis in human endometrial epithelial cells (hEECs). Subsequently, we sequenced and annotated the small RNA in MSC-exo and TGF-ß1-induced MSC-exo to screen for differentially expressed (DE) miRNAs. After the prediction and functional enrichment of target genes of DE miRNAs, key genes were selected for functional experiments. RESULTS: TGF-ß1 inhibited the proliferation of hEECs and promoted apoptosis and fibrosis. However, these effects were significantly reversed by the addition of MSC and MSC-exo. Fifteen DE miRNAs were identified by comparing the miRNA profiles of MSC-exo and TGF-ß1-induced MSC-exo. Among these, miR-145-5p was found to be significantly upregulated in TGF-ß1-induced MSC-exo. Furthermore, the addition of miR-145-5p mimic was found to reverse fibrosis in hEECs while promoting the expression of key autophagy protein P62. CONCLUSION: MSC-exo ameliorated TGF-ß1-induced endometrial fibrosis. RNA sequencing, bioinformatic analysis, and functional experiments revealed that miR-145-5p may exert its action through the P62-dependent autophagy pathway.
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OBJECTIVE: Individuals with Type 2 Diabetes are likely to experience multimorbidity and accumulate multiple chronic conditions over their life. We aimed to identify causes of death and chronic conditions at the time of death in a population-based cohort, and to analyze variations in the presence of diabetes at the time of death overall and across income and immigrant status. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 2,199,801 adult deaths from 1992 to 2017 in Ontario, Canada. We calculated the proportion of decedents with chronic conditions at time of death and causes of death. The risk of diabetes at the time of death was modeled across sociodemographic variables with a log binomial regression adjusting for sex, age, immigrant status, area-level income. comorbiditiesand time. RESULTS: The leading causes of death in the cohort were cardiovascular and cancer. Decedents with diabetes had a higher prevalence of most chronic conditions than decedents without diabetes, including hypertension, osteo and other arthritis, chronic coronary syndrome, mood disorder, and congestive heart failure. The risk of diabetes at the time of death was 19% higher in immigrants (95%CI 1.18-1.20) and 15% higher in refugees (95%CI 1.12-1.18) compared to long-term residents, and 19% higher in the lowest income quintile (95%CI 1.18-1.20) relative to the highest income quintile, after adjusting for other covariates. CONCLUSIONS: Individuals with diabetes have a greater multimorbidity burden at the time of death, underscoring the importance of multiple chronic disease management among those living with diabetes and further considerations of the social determinants of health.
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Diabetes Mellitus, Type 2 , Adult , Humans , Diabetes Mellitus, Type 2/epidemiology , Ontario/epidemiology , Multimorbidity , Retrospective Studies , Chronic DiseaseABSTRACT
INTRODUCTION: Patients with diabetes have a higher risk of mortality compared with the general population. Large population-based studies that quantify variations in mortality risk for patients with diabetes among subgroups in the population are lacking. This study aimed to examine the sociodemographic differences in the risk of all-cause mortality, premature mortality, and cause-specific mortality in persons diagnosed with diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based cohort study of 1 741 098 adults diagnosed with diabetes between 1994 and 2017 in Ontario, Canada using linked population files, Canadian census, health administrative and death registry databases. We analyzed the association between sociodemographics and other covariates on all-cause mortality and premature mortality using Cox proportional hazards models. A competing risk analysis using Fine-Gray subdistribution hazards models was used to analyze cardiovascular and circular mortality, cancer mortality, respiratory mortality, and mortality from external causes of injury and poisoning. RESULTS: After full adjustment, individuals with diabetes who lived in the lowest income neighborhoods had a 26% (HR 1.26, 95% CI 1.25 to 1.27) increased hazard of all-cause mortality and 44% (HR 1.44, 95% CI 1.42 to 1.46) increased risk of premature mortality, compared with individuals with diabetes living in the highest income neighborhoods. In fully adjusted models, immigrants with diabetes had reduced risk of all-cause mortality (HR 0.46, 95% CI 0.46 to 0.47) and premature mortality (HR 0.40, 95% CI 0.40 to 0.41), compared with long-term residents with diabetes. Similar HRs associated with income and immigrant status were observed for cause-specific mortality, except for cancer mortality, where we observed attenuation in the income gradient among persons with diabetes. CONCLUSIONS: The observed mortality variations suggest a need to address inequality gaps in diabetes care for persons with diabetes living in the lowest income areas.
Subject(s)
Diabetes Mellitus , Neoplasms , Adult , Humans , Ontario/epidemiology , Mortality, Premature , Cause of Death , Cohort Studies , Diabetes Mellitus/epidemiologyABSTRACT
BACKGROUND: Hyperkalemia increases the risk of mortality and cardiovascular-related hospitalizations in patients with hemodialysis. Predictors of hyperkalemia are yet to be identified. We aimed at developing a nomogram able to predict hyperkalemia in patients with hemodialysis. METHODS: We retrospectively screened patients with end-stage renal disease (ESRD) who had regularly received hemodialysis between Jan 1, 2017, and Aug 31, 2021, at Lishui municipal central hospital in China. The outcome for the nomogram was hyperkalemia, defined as serum potassium [K+] ≥ 5.5 mmol/L. Data were collected from hemodialysis management system. Least Absolute Shrinkage Selection Operator (LASSO) analysis selected predictors preliminarily. A prediction model was constructed by multivariate logistic regression and presented as a nomogram. The performance of nomogram was measured by the receiver operating characteristic (ROC) curve, calibration diagram, and decision curve analysis (DCA). This model was validated internally by calculating the performance on a validation cohort. RESULTS: A total of 401 patients were enrolled in this study. 159 (39.65%) patients were hyperkalemia. All participants were divided into development (n = 256) and validation (n = 145) cohorts randomly. Predictors in this nomogram were the number of hemodialysis session, blood urea nitrogen (BUN), serum sodium, serum calcium, serum phosphorus, and diabetes. The ROC curve of the training set was 0.82 (95%CI 0.77, 0.88). Similar ROC curve was achieved at validation set 0.81 (0.74, 0.88). The calibration curve demonstrated that the prediction outcome was correlated with the observed outcome. CONCLUSION: This nomogram helps clinicians in predicting the risk of PEW and managing serum potassium in the patients with hemodialysis.
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Hyperkalemia , Nomograms , Humans , Retrospective Studies , Cohort Studies , Renal Dialysis , PotassiumABSTRACT
This study uses administrative health care data from Ontario, Canada, to assess whether changes in diabetes management practices have affected trends in the association between diabetes vs prior cardiovascular disease and risk of cardiovascular events from 1994 to 2019 among adults aged 20 to 84 years.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Humans , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Ontario/epidemiologyABSTRACT
Thermal radiation has applications in numerous fields, such as radiation cooling, thermal imaging, and thermal camouflage. Micro/nanostructures such as chiral metamaterials with polarization-dependent or symmetry-breaking properties can selectively emit circularly (spin) polarized polarization waves. In this paper, we propose and demonstrate the spinning thermal radiation from two twisted different anisotropic materials. Taking industrial polymer and biaxial hyperbolic material α-MoO3 as an example, it is found that broadband spinning thermal radiation can be obtained from 13 µm to 18 µm. The spin thermal radiation of the proposed twisted structure originates from the combined effect of polarization conversion of circularly polarized wave and selective absorption of linearly polarized wave by the top and bottom layers of anisotropic materials, respectively. Besides, the narrowband spinning thermal radiation with 0.9 circular dichroism is achieved at wavelength of 12.39 µm and 18.93 µm for finite thickness α-MoO3 due to the epsilon-near-zero mode, and the magnetic field distribution can confirm the phenomenon. This work achieves broadband and narrowband spin thermal radiation and significantly enhances circular dichroism, which may have applications in biological sensing and thermal detection.
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Alcohol is one of the most commonly used addictive substances. Addiction memory is a necessary part of the mechanism underlying drug addiction. Lonicera japonica and its extract can mitigate organ damage caused by alcohol. In this study, Lonicera japonica polysaccharide (LJP) was extracted, and its effect on alcohol addiction memory was investigated. LJP inhibited the cue-induced reinstatement of conditioned place preference and elevated Tuj1 and DCX levels in the hippocampus to suppress neuronal damage. LJP also reduced the hippocampal glutamate (Glu) levels, alcohol-induced abnormal enhancement of the addiction memory, and decreased VPS34 phosphorylation and hyper activation of autophagy pathways in the hippocampus of alcohol-dependent mice. Our results suggest that LJP is a potential functional food to treat or ameliorate alcohol-induced addiction and that VPS34 is a potential target for modulating alcohol cravings.
Subject(s)
Lonicera , Animals , Dietary Carbohydrates , Ethanol , Hippocampus , Mice , Polysaccharides/pharmacology , Polysaccharides/therapeutic useABSTRACT
Plenty of pieces of evidence suggest that the resistance to radiotherapy greatly influences the therapeutic effect in cervical cancer (CCa). MicroRNAs (miRNAs) have been reported to regulate cellular processes by acting as tumor suppressors or promoters, thereby driving radioresistance or radiosensitivity. Meanwhile, it has been reported that microRNA-1323 (miR-1323) widely participates in cancer progression and radiotherapy effects. However, the role of miR-1323 is still not clear in CCa. Hence, in this study, we are going to investigate the molecular mechanism of miR-1323 in CCa cells. In the beginning, miR-1323 was found aberrantly upregulated in CCa cells via RT-qPCR assay. Functional assays indicated that miR-1323 was transferred by cancer-associated fibroblasts-secreted (CAFs-secreted) exosomes and miR-1323 downregulation suppressed cell proliferation, migration, invasion, and increased cell radiosensitivity in CCa. Mechanism assays demonstrated that miR-1323 targeted poly(A)-binding protein nuclear 1 (PABPN1). Besides, PABPN1 recruited insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to regulate glycogen synthase kinase 3 beta (GSK-3ß) and influenced Wnt/ß-catenin signaling pathway. Therefore, rescue experiments were implemented to validate that PABPN1 overexpression rescued the inhibited cancer development and radioresistance induced by the miR-1323 inhibitor. In conclusion, miR-1323 was involved in CCa progression and radioresistance which might provide a novel insight for CCa treatment.
Subject(s)
Cancer-Associated Fibroblasts , Exosomes , MicroRNAs , Uterine Cervical Neoplasms , Cancer-Associated Fibroblasts/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Exosomes/metabolism , Female , Gene Expression Regulation, Neoplastic , Glycogen Synthase Kinase 3 beta/metabolism , Humans , MicroRNAs/metabolism , Poly(A)-Binding Protein I/genetics , Poly(A)-Binding Protein I/metabolism , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/radiotherapy , Wnt Signaling Pathway/genetics , beta Catenin/metabolismABSTRACT
This study aimed to conduct a network meta-analysis (NMA) to compare the efficacy of brain natriuretic peptide (BNP) vs nicorandil for preventing contrast-induced nephropathy (CIN). Databases of Pubmed, Cochrane, Embase, Web of Science were searched by keywords for eligible studies of randomized controlled trials investigating different agents (BNP, nicorandil, nitroglycerin, intravenous saline) for preventing CIN. The outcomes included a change in serum creatinine level at 48 h and the incidence of CIN after percutaneous coronary intervention (PCI) or coronary angiography (CAG). A total of 13 studies with 3,462 patients were included. Compared with intravenous saline alone, except for nitroglycerin (odds ratio [OR]: 1.02, 95% CI [0.36-2.88]), the other drugs significantly reduced the CIN incidence with OR of 0.35 (95% CI [0.24-0.51]) for BNP, 0.52 (0.29, 0.94) for usual-dose nicorandil, 0.28 (0.19, 0.43) for double-dose nicorandil. BNP and double-dose nicorandil significantly decreased the change of serum creatinine (SCr) levels with mean difference (MD) of -6.98, (-10.01, -3.95) for BNP, -8.78, (-11.63, -5.93) for double-dose nicorandil. No significant differences were observed in the change of SCr levels for nitroglycerin (-4.97, [-11.46, 1.52]) and usual-dose nicorandil (-2.32, [-5.52, 0.89]) compared with intravenous saline alone. For double-dose nicorandil, the CIN incidence and the change of SCr level in group of 4-5 days treatment course were more than group of less than or equal to 24 h treatment course (OR of 1.48, [0.63-3.46] and MD of 2.48, [-1.96, 6.91]). In conclusion, BNP and double-dose nicorandil can have effects on preventing the incidence of CIN and double-dose nicorandil performed better than BNP. In double-dose nicorandil groups, a course of less than or equal to 24 h before and after procedure performed with better efficacy than a course of 4-5 days.
Subject(s)
Kidney Diseases , Percutaneous Coronary Intervention , Humans , Nicorandil/therapeutic use , Natriuretic Peptide, Brain/adverse effects , Contrast Media/adverse effects , Nitroglycerin/adverse effects , Percutaneous Coronary Intervention/adverse effects , Network Meta-Analysis , Creatinine/adverse effectsABSTRACT
OBJECTIVE: The aim of this study was to analyze the clinical features, risk factors, and outcomes of patients with primary nephrotic syndrome (PNS) who developed Pneumocystis pneumonia (PCP). MATERIALS AND METHODS: We systematically reviewed medical records from 18 PNS patients with PCP admitted to our hospital from April 2007 to April 2019. A total of 180 cases were randomly selected as controls from PNS inpatients without infection. RESULTS: In PCP patients, the mean age at presentation was 48.5 years, mean duration of prednisone treatment was 3.7 months, and mean prednisone dose on admission was 31.3 mg/d. Eight patients (44.4%) had coexisting infections, most often was Cytomegalovirus (4 patients); 11 patients (61.1%) had ICU admission, and 9 patients (50%) had mechanical ventilation. PCP patients had more prednisone, more immunosuppressive therapy, lower CD4+ cell counts and hemoglobin, and higher serum creatinine than those without infections (p < 0.05). All patients survived after treatment. CONCLUSION: PCP was not unusual in PNS patients, and the most important risk factors were prednisone usage, other immunosuppressive therapy, and a lower CD4+ cell count; however, these patients had a good outcome after sufficient treatment.
Subject(s)
Nephrotic Syndrome , Pneumonia, Pneumocystis , Humans , Nephrotic Syndrome/complications , Nephrotic Syndrome/drug therapy , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/epidemiology , Prednisone/therapeutic use , Respiration, Artificial , Retrospective Studies , Risk FactorsABSTRACT
The development of an efficient photocatalyst with superior activity under visible light has been regarded as a significant strategy for pollutant degradation and environmental remediation. Herein, a series of WO3/Ag2CO3 mixed photocatalysts with different proportions were prepared by a simple mixing method and characterized by XRD, SEM, TEM, XPS, and DRS techniques. The photocatalytic performance of the WO3/Ag2CO3 mixed photocatalyst was investigated by the degradation of rhodamine B (RhB) under visible light irradiation (λ > 400 nm). The photocatalytic efficiency of the mixed WO3/Ag2CO3 photocatalyst was rapidly increased with the proportion of Ag2CO3 up to 5%. The degradation percentage of RhB by WO3/Ag2CO3-5% reached 99.7% within 8 min. The pseudo-first-order reaction rate constant of WO3/Ag2CO3-5% (0.9591 min-1) was 118- and 14-fold higher than those of WO3 (0.0081 min-1) and Ag2CO3 (0.0663 min-1). The catalytic activities of the mixed photocatalysts are not only higher than those of the WO3 and Ag2CO3 but also higher than that of the WO3/Ag2CO3 composite prepared by the precipitation method. The activity enhancement may be because of the easier separation of photogenerated electron-hole pairs. The photocatalytic mechanism was investigated by free radical capture performance and fluorescence measurement. It was found that light-induced holes (h+) was the major active species and superoxide radicals (·O2 -) also played a certain role in photocatalytic degradation of RhB.