ABSTRACT
To investigate the dynamic homing process and characteristics of macrophages in different organs of immune-mediated aplastic anemia (AA) model mice. Macrophages in donor lymph nodes were sorted by magnetic beads and labeled with PKH67. After modeling according to the preparation method of the AA model, peripheral blood rountine analysis, bone marrow biopsy and HE staining results were analyzed to verify the modeling effect. On days 4, 8, and 12 of modeling, the bone marrow, spleen, and lymph node mononuclear cells were collected, and dynamic changes of PKH67-labeled macrophages in donor mice were analyzed by flow cytometry. In this study, dynamic changes in PKH67-labeled macrophages in the pathogenesis of AA model mice were explored. Macrophages in donor mice homed to the lymph nodes, expanding and differentiating in the lymph nodes, and finally transported to the bone marrow and spleen. Through proteomics mass spectrometry analysis, the related immune inflammatory response pathway of macrophages involved in the activation of the AA bone marrow microenvironment was preliminarily revealed, which provides a basis for the pathological macrophages involved in the pathogenesis of AA model mice.
Subject(s)
Anemia, Aplastic , Disease Models, Animal , Macrophages , Animals , Mice , Anemia, Aplastic/immunology , Macrophages/immunology , Male , Spleen/cytology , Spleen/immunology , Lymph Nodes/immunology , Lymph Nodes/cytology , Bone Marrow/pathologyABSTRACT
Objective: To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts. Methods: C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry. Results: On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant (Pï¼0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all Pï¼0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8+ T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, Pï¼0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, Pï¼0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, Pï¼0.05]. The proportion, of CD4+ T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, Pï¼0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, Pï¼0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all Pï¼0.05). Conclusion: High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.
Subject(s)
Carcinoma, Lewis Lung , Diet, Carbohydrate-Restricted , Diet, High-Fat , Mice, Inbred C57BL , Tumor Microenvironment , Animals , Carcinoma, Lewis Lung/radiotherapy , Carcinoma, Lewis Lung/metabolism , Mice , Diet, High-Fat/adverse effects , Diet, Carbohydrate-Restricted/methods , Tumor Burden , Lung Neoplasms/radiotherapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathologyABSTRACT
Background: Acute kidney injury (AKI) is a major contributor to end-stage kidney disease (ESKD). About one-third of patients with ESKD due to AKI recover kidney function. However, the inability to accurately predict recovery leads to improper triage of clinical monitoring and impacts the quality of care in ESKD. Methods: Using data from the United States Renal Data System from 2005 to 2014 (n = 22 922), we developed a clinical score to predict kidney recovery within 90 days and within 12 months after dialysis initiation in patients with ESKD due to AKI. Multivariable logistic regressions were used to examine the effect of various covariates on the primary outcome of kidney recovery to develop the scoring system. The resulting logistic parameter estimates were transformed into integer point totals by doubling and rounding the estimates. Internal validation was performed. Results: Twenty-four percent and 34% of patients with ESKD due to AKI recovered kidney function within 90 days and 12 months, respectively. Factors contributing to points in the two scoring systems were similar but not identical, and included age, race/ethnicity, body mass index, congestive heart failure, cancer, amputation, functional status, hemoglobin and prior nephrology care. Three score categories of increasing recovery were formed: low score (0-6), medium score (7-9) and high score (10-12), which exhibited 90-day recovery rates of 12%, 26% and 57%. For the 12-month scores, the low, medium and high groups consisted of scores 0-5, 6-8 and 9-11, with 12-month recovery rates of 16%, 33% and 62%, respectively. The internal validation assessment showed no overfitting of the models. Conclusion: A clinical score derived from information available at incident dialysis predicts renal recovery at 90 days and 12 months in patients with presumed ESKD due to AKI. The score can help triage appropriate monitoring to facilitate recovery and begin planning long-term dialysis care for others.
ABSTRACT
PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Intravitreal Injections , Ranibizumab , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Renal Insufficiency , Vascular Endothelial Growth Factor A , Humans , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Ranibizumab/administration & dosage , Ranibizumab/adverse effects , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Retrospective Studies , Male , Female , Renal Insufficiency/epidemiology , Renal Insufficiency/complications , Renal Insufficiency/chemically induced , Incidence , Aged , Middle Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/complications , Follow-Up Studies , Risk Factors , Macular Edema/drug therapy , Macular Edema/epidemiology , Macular Edema/diagnosis , Retinal Vein Occlusion/drug therapy , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/epidemiology , Blindness/epidemiology , Blindness/chemically induced , Blindness/prevention & control , Blindness/diagnosis , Blindness/etiologyABSTRACT
Three ΔI=1 bands with the πg_{9/2}âνg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.
ABSTRACT
AKI survivors experience gaps in care that contribute to worse outcomes, experience, and cost.Challenges to optimal care include issues with information transfer, education, collaborative care, and use of digital health tools.Research is needed to study these challenges and inform optimal use of diagnostic and therapeutic interventions to promote recovery AKI affects one in five hospitalized patients and is associated with poor short-term and long-term clinical and patient-centered outcomes. Among those who survive to discharge, significant gaps in documentation, education, communication, and follow-up have been observed. The American Society of Nephrology established the AKINow taskforce to address these gaps and improve AKI care. The AKINow Recovery workgroup convened two focus groups, one each focused on dialysis-independent and dialysis-requiring AKI, to summarize the key considerations, challenges, and opportunities in the care of AKI survivors. This article highlights the discussion surrounding care of AKI survivors discharged without the need for dialysis. On May 3, 2022, 48 patients and multidisciplinary clinicians from diverse settings were gathered virtually. The agenda included a patient testimonial, plenary sessions, facilitated small group discussions, and debriefing. Core challenges and opportunities for AKI care identified were in the domains of transitions of care, education, collaborative care delivery, diagnostic and therapeutic interventions, and digital health applications. Integrated multispecialty care delivery was identified as one of the greatest challenges to AKI survivor care. Adequate templates for communication and documentation; education of patients, care partners, and clinicians about AKI; and a well-coordinated multidisciplinary posthospital follow-up plan form the basis for a successful care transition at hospital discharge. The AKINow Recovery workgroup concluded that advancements in evidence-based, patient-centered care of AKI survivors are needed to improve health outcomes, care quality, and patient and provider experience. Tools are being developed by the AKINow Recovery workgroup for use at the hospital discharge to facilitate care continuity.
Subject(s)
Acute Kidney Injury , Patient Discharge , Humans , Renal Dialysis , Continuity of Patient Care , Survivors , Acute Kidney Injury/diagnosis , Acute Kidney Injury/therapyABSTRACT
BACKGROUND: Up to one third of survivors of AKI that required dialysis (AKI-D) during hospitalization remain dialysis dependent at hospital discharge. Of these, 20%-60%, depending on the clinical setting, eventually recover enough kidney function to stop dialysis, and the remainder progress to ESKD. METHODS: To describe the challenges facing those still receiving dialysis on discharge, the AKINow Committee conducted a group discussion comprising 59 participants, including physicians, advanced practitioners, nurses, pharmacists, and patients. The discussion was framed by a patient who described gaps in care delivery at different transition points and miscommunication between care team members and the patient. RESULTS: Group discussions collected patient perspectives of ( 1 ) being often scared and uncertain about what is happening to and around them and ( 2 ) the importance of effective and timely communication, a comfortable physical setting, and attentive and caring health care providers for a quality health care experience. Provider perspectives included ( 1 ) the recognition of the lack of evidence-based practices and quality indicators, the significant variability in current care models, and the uncertain reimbursement incentives focused on kidney recovery and ( 2 ) the urgency to address communication barriers among hospital providers and outpatient facilities. CONCLUSIONS: The workgroup identified key areas for future research and policy change to ( 1 ) improve communication among hospital providers, dialysis units, and patients/care partners; ( 2 ) develop tools for risk classification, subphenotyping, and augmented clinical decision support; ( 3 ) improve education to providers, staff, and patients/care partners; ( 4 ) identify best practices to improve relevant outcomes; ( 5 ) validate quality indicators; and ( 6 ) assess the effect of social determinants of health on outcomes. We urge all stakeholders involved in the process of AKI-D care to align goals and work together to fill knowledge gaps and optimize the care to this highly vulnerable patient population.
Subject(s)
Acute Kidney Injury , Renal Dialysis , Humans , Outpatients , Acute Kidney Injury/therapy , Acute Kidney Injury/epidemiology , Kidney , Delivery of Health CareABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging as a leading etiology of chronic liver disease (CLD) in Asia. The increasing incidence of NAFLD is projected to drive a surge in NAFLD-related hepatocellular carcinoma (HCC). A notable characteristic of NAFLD-HCC is its capacity for development in individuals without cirrhosis in more than a third of patients. Most practice guidelines recommend biannual ultrasound screening for patients with cirrhosis. In cases of severe limitations to ultrasound visualisation, cross-sectional abdominal imaging may be warranted. Improved strategies for HCC risk stratification are required for people with NAFLD but without cirrhosis. In this Review, we discuss the evolving trends of NAFLD and HCC in Asia, and implications for surveillance.
ABSTRACT
Cyanobacterial harmful algal blooms (cHABs) have the potential to adversely affect public health through the production of toxins such as microcystins, which consist of numerous molecularly distinct congeners. Microcystins have been observed in the atmosphere after emission from freshwater lakes, but little is known about the health effects of inhaling microcystins and the factors contributing to microcystin aerosolization. This study quantified total microcystin concentrations in water and aerosol samples collected around Grand Lake St. Marys (GLSM), Ohio. Microcystin concentrations in water samples collected on the same day ranged from 13 to 23 µg/L, dominated by the d-Asp3-MC-RR congener. In particulate matter <2.5 µm (PM2.5), microcystin concentrations up to 156 pg/m3 were detected; the microcystins were composed primarily of d-Asp3-MC-RR, with additional congeners (d-Asp3-MC-HtyR and d-Asp3-MC-LR) observed in a sample collected prior to a storm event. The PM size fraction containing the highest aerosolized MC concentration ranged from 0.44 to 2.5 µm. Analysis of total bacteria by qPCR targeting 16S rDNA revealed concentrations up to 9.4 × 104 gc/m3 in aerosol samples (≤3 µm), while a marker specific to cyanobacteria was not detected in any aerosol samples. Concentrations of aerosolized microcystins varied even when concentrations in water were relatively constant, demonstrating the importance of meteorological conditions (wind speed and direction) and aerosol generation mechanism(s) (wave breaking, spillway, and aeration systems) when evaluating inhalation exposure to microcystins and subsequent impacts on human health.
Subject(s)
Cyanobacteria , Harmful Algal Bloom , Humans , Microcystins/analysis , Cyanobacteria Toxins , Lakes/analysis , Lakes/microbiology , Aerosols , Water , Atmosphere/analysisABSTRACT
Objective: To perform a health economic evaluation of telemedicine diabetic retinopathy (DR) examination with a non-mydriatic fundus camera in China and to investigate the optimal examination interval. Methods: Based on 18 peer-reviewed articles related to epidemiology, clinical trial, and health economic evaluation of DR, surveys from 9 ophthalmologists in 3 tertiary hospitals in China, price lists for medical services in each province, and the negotiated price in 2021, a Markov model was conducted to evaluate the cost utility of telemedicine eye examination for diabetes mellitus patients aged 45 and older from the health system perspective. Separate analyses were performed for no examination and for examination intervals of every 1 to 5 years to predict the lifetime health gain, including cumulative days of blindness, cumulative life years, and quality-adjusted life years (QALYs), and costs for unilateral and bilateral direct medication with a 3.5% discount rate. Results: The cumulative days of blindness in the absence of a DR screening were 2 375.00 days, and ranged from 701.00 to 738.00 days for five different DR screening interval programs. The cumulative life years for no screening and five DR screening programs ranged from 27.120 34 to 28.005 00 years, with QALYs ranging from 9.502 96 to 9.875 02. The direct medication costs in the absence of a DR screening program were 72 785.00 yuan for both unilateral and bilateral scenarios. For the five DR screening intervals, the direct medication costs ranged from 52 065.00 to 52 408.00 yuan for unilateral and 79 100.00 to 79 603.00 yuan for bilateral. Comparing the incremental cost-effectiveness ratios between the DR screening intervals and no screening, the 1-to 5-year intervals were dominant in the unilateral scenario (between -56 368.54 and -55 523.75 yuan/QALY). In the bilateral scenario, the ratios ranged from 17 469.07 to 18 325.15 yuan/QALY. Using a willingness-to-pay threshold equal to the per capita GDP (80 976 yuan/QALY), the 1-year DR screening interval had an 85.9% probability of being cost-effective and a 55.2% probability of being dominant in the unilateral scenario. In the bilateral scenario, the 2-year interval held a 61.4% probability of being cost-effective. Conclusions: Analyses on the remote fundus consultation in diabetic patients and health economics based on the Markov model indicate that telemedicine DR examination through a non-mydriatic fundus camera can be effectively employed for diabetes mellitus patients in China. DR examination every two years is recommended for general diabetic patients, and DR examination every year may be chosen in developed areas.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Telemedicine , Humans , Cost-Benefit Analysis , Diabetic Retinopathy/diagnosis , Mass Screening , Blindness , ChinaABSTRACT
Aims: Hip fractures are a major cause of morbidity and mortality, and malnutrition is a crucial determinant of these outcomes. This meta-analysis aims to determine whether oral nutritional supplementation (ONS) improves postoperative outcomes in older patients with a hip fracture. Methods: A systematic literature search was conducted in August 2022. ONS was defined as high protein-based diet strategies containing (or not containing) carbohydrates, fat, vitamins, and minerals. Randomized trials documenting ONS in older patients with hip fracture (aged ≥ 50 years) were included. Two reviewers evaluated study eligibility, conducted data extraction, and assessed study quality. Results: There were 812 studies identified, of which 18 studies involving 1,522 patients met the inclusion criteria. The overall meta-analysis demonstrated that ONS was associated with significantly elevated albumin levels (weighted mean difference (WMD) 1.24 (95% confidence interval (CI) 0.95 to 1.53)), as well as a significant risk reduction in infective complications (odds ratio (OR) 0.54 (95% CI 0.39 to 0.76)), pressure ulcers (OR 0.54 (95% CI 0.33 to 0.88)), and total complications (OR 0.57 (95% CI 0.42 to 0.79)). Length of hospital stay (LOS) was also significantly reduced (WMD -2.36 (95% CI -4.14 to -0.58)), particularly in rehabilitation LOS (WMD -4.17 (95% CI -7.08 to -1.26)). There was a tendency towards a lower mortality risk (OR 0.93 (95% CI 0.62 to 1.4)) and readmission (OR 0.52 (95% CI 0.16 to 1.73)), although statistical significance was not achieved (p = 0.741 and p = 0.285, respectively). The overall compliance with ONS ranged from 64.7% to 100%, but no factors influencing compliance were identified. Conclusion: This meta-analysis is the first to quantitatively demonstrate that ONS could nearly halve the risk of infective complications, pressure ulcers, total complications, as well as improve serum albumin and reduce LOS. ONS should be a regular and integrated part of the perioperative care of these patients, especially given that the compliance with ONS is acceptable.
Subject(s)
Hip Fractures , Malnutrition , Pressure Ulcer , Humans , Aged , Pressure Ulcer/complications , Dietary Supplements , Malnutrition/complications , Length of StayABSTRACT
OBJECTIVE: To investigate the effect of Erchen Decoction on iron homeostasis in mice with nonalcoholic fatty liver disease (NAFLD) and its mechanism for regulating iron transport in spleen cells. METHODS: Thirty male C57BL/6J mice were given a high-fat diet for 12 weeks and randomized (n=6) at the 7th week for gavage (3 times a week) of drinking water (NAFLD model group), Erchen Decoction at low, medium and high doses (7.5, 15, and 30g/kg, respectively), or polyene phosphatidyl choline (PPC; 9.12 mg/kg), with another 6 mice with low-fat and low-sugar feeding as the control group. The active components of Erchen Decoction were determined by HPLC-MS. Lipid accumulation in the liver was evaluated by HE staining and Nile red staining. Prussian blue staining was used to observe iron content in the spleen. The iron ion content in the liver tissue was detected using a detection kit. The expressions of ferroportin1 (Fpn1), transferrin receptor (TfR), Steap3, HO-1, Ter-119, CD163 and CD68 were detected using Western blotting, immunohistochemistry and immunofluorescence staining. RESULTS: Medium- and high-dose Erchen Decoction partially reversed the increase of lipid accumulation in the liver of NAFLD mice and showed better lipid-lowering effect than PPC. The NAFLD mice showed significantly decreased iron ion content in the spleen with increased hepatic and serum iron contents (P < 0.05), decreased TfR protein expression (P < 0.05), and increased Fpn1 and Steap3 protein expressions (P < 0.05), and these changes were significantly improved by the drug interventions. Erchen Decoction also improved the function of CD163 macrophages in the spleen of NAFLD mice by up-regulating the expression of HO-1 (P < 0.05). CONCLUSION: Erchen Decoction can alleviate high-fat diet-induced iron metabolism disorder by improving the iron ion transport ability of the spleen cells to delay the progression of NAFLD.
Subject(s)
Non-alcoholic Fatty Liver Disease , Spleen , Male , Animals , Mice , Mice, Inbred C57BL , Ion Transport , Homeostasis , LipidsABSTRACT
Rationale & Objective: Patients with advanced chronic kidney disease (CKD) and their care partners experienced decreased access to care, and worse physical and emotional health during the Coronavirus Disease-19 (COVID-19) pandemic. Few studies have explored how COVID-19-related challenges affected disease self-management among those with advanced chronic kidney disease (CKD) and their care partners. Leventhal's self-regulation model offers a comprehensive framework for understanding disease self-management through the interplay of cognitive beliefs, emotional reactions and social influences. The study aims to examine the impact of COVID-19 on self-management activities among patients with CKD and care partners. Study Design: Qualitative study. Setting & Participants: Adults with advanced CKD, including dialysis and transplant recipients, and their carepartners. Analytical Approach: Thematic Analysis. Results: Among 42 participants, 12 had stage 4 CKD, 5 had stage 5 CKD, 6 were receiving in-center hemodialysis, 5 had a kidney transplant, and 14 were care partners. We identified 4 patient-related themes with corresponding subthemes related to the impact of COVID-19 on self-management: 1) cognitive understanding that COVID-19 is an additional health threat to existing kidney disease, 2) heightened anxiety and vulnerability driven by perceived risk, 3) coping with isolation through virtual interactions with healthcare services and social circles, 4) increased protective behaviors to maximize survival. Three care partner-related themes emerged: 1) hypervigilance in family care and protection, 2) interaction with health system and adaptations to self-management, and 3) increased intensity in caregiving role to facilitate patient self-management. Limitations: The qualitative study design limits the ability to generate generalizable data. Grouping patients with Stage 3 and 4 CKD, in-center hemodialysis, and kidney transplants together limited our ability to examine self-management challenges specific to each treatment requirement. Conclusions: When faced with the COVID-19 pandemic, patients with CKD and their care partners experienced heightened vulnerability and thus increased cautionary activities to maximize survival. Our study provides the groundwork for future interventions to help patients and care partners live with kidney disease during future crises.
ABSTRACT
OBJECTIVES: Sarcopenia is recognized as a major public health concern because of its association with several adverse health events. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation reportedly delays the loss of muscle mass and function; however, the effect of HMB on sarcopenia remains inconclusive. We aimed to evaluate the impact of HMB intervention on muscle strength, physical performance, body compositions, and inflammatory factors in older adults with sarcopenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING AND PARTICIPANTS: This study included subjects aged ≥60 years with sarcopenia which were assigned to the HMB group (HMBG, n=18) and the placebo group (PG, n=16). INTERVENTION: The HMBG and PG were supplied with HMB and placebo products twice daily for 12 weeks, and both received resistance exercise training twice a week in 12 weeks. MEASUREMENTS: Hand grip strength was selected as the primary outcome; gait speed, five-time chair stand test, body composition and inflammatory indicators were selected as the secondary outcomes. The differences in changes from baseline between the two groups were analyzed using the analysis of covariance(ANCOVA). RESULTS: After the 12-week intervention, the HMBG demonstrated significantly greater improvements in handgrip strength (4.61(95%CI:2.93,6.28) kg, P<0.001), gait speed (0.11(95%CI:0.02,0.20)m/s, P=0.014), five-time chair stand test (-3.65 (95%CI:-5.72, -1.58)s, P=0.001), muscle quality (2.47(95%CI:1.15,3.80),kg.kg-1 P=0.001) and tumor necrosis factor-like weak inducer of apoptosis (-15.23(95%CI:-29.80,-0.66)pmol/mL, P=0.041) compared with the PG; no significant differences in skeletal muscle mass, skeletal muscle index, and other body composition parameters were found between the two groups. CONCLUSION: In older adults with sarcopenia, HMB significantly enhance the effect of resistance exercise training on muscle strength, physical performance, muscle quality, and reduced inflammatory factors. Therefore, HMB supplementation could be an effective treatment for sarcorpenia. The trial protocol was registered at http://www.chictr.org.cn/showproj.aspx?proj=47571 as ChiCTR2000028778.
Subject(s)
Sarcopenia , Humans , Aged , Sarcopenia/drug therapy , Hand Strength/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Double-Blind Method , Dietary SupplementsABSTRACT
To give full play to the important role of courses for ideological and political education in moral cultivation, teaching group in the course of oral histology and pathology in Zhejiang University systematically studied the teaching model of which ideological and political education integrated into the course of oral histology and pathology, and put forward a quality evaluation index system of the course. This paper emphatically introduces the general framework of the course, as well as the experience and practices in the aspects of resource mining, teaching design, curriculum evaluation, etc. The quality of the course was evaluated by using the system, which showed that the grade of the course was AAA (excellent) and 95.5% (275/288) students agreed to integrate ideological and political content into the course. The teaching group believes that the integration of the ideological and political content in the course reflects the complementary effect of "teaching" and "educating", and the ideological and political quality as well as the professional level of the teachers are the primary factor to determine the quality of the course. This paper aims at providing a reliable reference for promoting the construction of courses for ideological and political education in the area of oral medical education.
ABSTRACT
BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a more severe subtype of nonalcoholic fatty liver disease, can cause cirrhosis and hepatocellular carcinoma. Macrophages play critical roles in initiating and maintaining NASH-induced liver inflammation and fibrosis. However, the underlying molecular mechanism of macrophage chaperone-mediated autophagy (CMA) in NASH remains unclear. We aimed to investigate the effects of macrophage-specific CMA on liver inflammation and identify a potential therapeutic target for NASH treatment. METHODS: The CMA function of liver macrophages was detected using Western blot, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and flow cytometry. By constructing myeloid-specific CMA deficiency mice, we evaluated the effects of deficient CMA of macrophages on monocyte recruitment, liver injury, steatosis and fibrosis in NASH mice. A label-free mass spectrometry was utilized to screen the substrates of CMA in macrophages and their mutual interactions. The association between CMA and its substrate was further examined by immunoprecipitation, Western blot and RT-qPCR. RESULTS: A typical hallmark in murine NASH models was impaired CMA function in hepatic macrophages. Monocyte-derived macrophages (MDM) were the dominant macrophage population in NASH, and CMA function was impaired in MDM. CMA dysfunction aggravated liver-targeted recruitment of monocyte and promoted steatosis and fibrosis. Mechanistically, Nup85 functions as a substrate for CMA and its degradation was inhibited in CMA-deficient macrophages. Inhibition of Nup85 attenuated the steatosis and monocyte recruitment caused by CMA deficiency in NASH mice. CONCLUSIONS: We proposed that the impaired CMA-induced Nup85 degradation aggravated monocyte recruitment, promoting liver inflammation and disease progression of NASH.
Subject(s)
Chaperone-Mediated Autophagy , Non-alcoholic Fatty Liver Disease , Nuclear Pore Complex Proteins , Animals , Mice , Disease Models, Animal , Fibrosis , Inflammation/pathology , Liver/pathology , Macrophages/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/pathology , Nuclear Pore Complex Proteins/metabolismABSTRACT
African swine fever virus (ASFV) causes feverous and hemorrhagic disease of domestic pigs and European wild boars with high mortality, yet no commercial vaccine is currently available. Several ASFV strains with natural deletion or gene-targeted knockout of multiple MGF360 and MGF505 genes are attenuated in vitro and in vivo, and can offer full protection against homologous challenge. However, the mechanisms underlying the protection are not fully understood. This study aims to investigate the effects of MGF360-12L of ASFV-SY18 on the cGAS-STING signaling pathway and explore the potential mechanisms. We identified that ASFV-SY18 MGF360-12L could inhibit cGAS-STING, TBK1, or IRF3-5D-stimulated IFN-ß expression and ISRE activation. Specifically, MGF360-12L inhibits both the activation of PRD(III-I) in a dose-dependent manner, and suppresses the exogenous expression of TBK1 and IRF3-5D. MGF360-12L could block NF-κB activation induced by overexpression of cGAS-STING, TBK1, IKKß. Downstream of the IFN-ß signaling, MGF360-12L blocks the ISRE promoter activation by reducing total protein level of IRF9. Moreover, MGF360-12L protein can inhibit IFN-ß-mediated antiviral effects. In conclusion, our findings suggest that MGF360-12L is a multifunctional immune-evasion protein that inhibits both the expression and effect of IFN-ß, which could partially explain the attenuation of relevant gene-deleted ASFV strains, and shed light on the development of efficient ASFV live attenuated vaccines in the future.