ABSTRACT
Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder.
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Ferroptosis in tubules has been implicated in the pathogenesis of acute kidney injury (AKI), whereas the regulatory mechanism remains unclear. The stimulator of interferon genes (STING) is previously recognized as a critical mediator of innate immunity via a DNA-sensing pathway and has been increasingly linked to lipid peroxidation, a hallmark of ferroptosis. Herein we investigated the role and the underlying mechanism of STING in AKI models established by ischemia/reperfusion (IR) in C57BL mice. The expression level of STING was predominantly increased in tubules of kidney after IR treatment. Besides, STING deficiency markedly alleviated IR-induced lipid peroxidation, tissue damage and renal dysfunction. Consistently, in vitro experiments demonstrated that the increase in ferroptotic cell death, lipid ROS production and the decrease in GSH peroxidase 4 (GPX4) expression in renal tubular cells subjected to ferroptosis agonist or hypoxia/reoxygenation intervention were all mitigated by genetic deficiency or pharmacological inhibition of STING, while all exacerbated by STING overexpression. Further, these detrimental effects of STING overexpression relied on the induction of ferritinophagy, i.e. autophagic degradation of ferritin, leading to iron overload. Mechanistically, STING mediated the initiation of ferritinophagy through interacting with nuclear receptor coactivator 4 (NCOA4), a fundamental receptor for the transfer of ferritin into lysosome. Collectively, STING contributes to ferroptosis during ischemic AKI through facilitating NCOA4-mediated ferritinophagy and shows the potential as a promising therapeutic choice for AKI.
Subject(s)
Acute Kidney Injury , Ferroptosis , Animals , Mice , Acute Kidney Injury/genetics , Ferritins , Ferroptosis/genetics , Kidney , Mice, Inbred C57BLABSTRACT
In order to fully investigate the anti-aging value of the plants polysaccharides, the fermentation method was applied to modify the Polygonatum kingianum polysaccharides (PKPS), and the ultra-filtration was used to further segment the hydrolyzed polysaccharides. It was found that the fermentation induced an increase in the in vitro anti-aging-related activities of PKPS including antioxidant, hypoglycemic and hypolipidemic activity, and cellular aging-delaying ability. In particular, the low Mw fraction PS2-4 (10-50 kDa) separated from the fermented polysaccharide exhibited superior anti-aging activity on experimental animals. PS2-4 extended the Caenorhabditis elegans lifespan by 20.70 %, with an increased effect of 10.09 % compared to the original polysaccharide; it was also more effective than the original one in improving movement ability and reducing lipofuscin accumulation of worms. This fraction was screened as the optimal anti-aging active polysaccharide. After fermentation, the main molecular weight distribution of PKPS changed from 50-650 kDa to 2-100 kDa, and the chemical composition and monosaccharide composition also changed; the initial rough and porous microtopography turned into smooth state. These alterations in physicochemical characteristics suggest that fermentation exerted an influence on the structure of PKPS, which contributed to the enhanced anti-aging activity, indicating that fermentation was promising in the structural modification of polysaccharides.
Subject(s)
Polygonatum , Animals , Polygonatum/chemistry , Fermentation , Polysaccharides/pharmacology , Polysaccharides/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , AgingABSTRACT
The sea cucumber peptides (SCPs) from Acaudina leucoprocta were derived from the patented bio-enzyme digestion technology and the molecular weight of obtained SCPs was < 10 kDa. In this study, we investigated the possible anti-aging effects of SCPs on the model of Caenorhabditis elegans and the underlying mechanisms. SCPs extend the average lifespan of nematodes by 31.46%. SCPs enhance the anti-stress capacity of C. elegans by improving heat resistance and mobility, Also, the accumulated potential oxidative stress inducers like lipofuscin and reactive oxygen species (ROS) were reduced to 40.84 and 71.43%. In addition, SCPs can increase the antioxidant capacity in nematodes by enhancing the activity of SOD and CAT and reducing MDA accumulation in nematodes to 32.44%. Mechanistically, SCPs could mediate DAF-16/DAF-2/SOD-3/OLD-1/PEPT-1 axis to improve antioxidant capacity and extend lifespan in nematodes. Taken together, these findings provide a direction for the anti-aging effects of sea cucumber peptides and new insights into the further purifications of SCPs and future research on aging.
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BACKGROUND: Cancer palliative care is recommended by guidelines for patients with early stage of cancer. Unlike the Western countries, in mainland China, cancer patients receive specialist-led cancer palliative care. Nurse-led cancer palliative care (NUC) is not well established yet. OBJECTIVES: To compare the clinical outcome measures, quality of life and symptom distress in patients suffering from cancer who received NUC with the same results in patient who received consulting oncologist-led cancer palliative care (ONC). MATERIAL AND METHODS: The study was a chart review of a database of patients suffering from cancer. Data regarding clinical outcome measures, quality of life and symptom distress of patients suffering from cancer who were receiving chemotherapy and NUC (NUC cohort, n = 185) or ONC (ONC cohort, n = 170) were collected and analyzed. One oncologist or 1 nurse was involved in treating 1 patient during the patient's hospital visit. Each visit took 30 min. The Chinese version of the Symptom Distress Scale was used for the evaluation of the degree of symptom distress. The simplified Chinese version of the European Organization for Research and Treatment Quality of Life Questionnaire (the EORTC QLQ-C30) v. 3.0 was used for evaluation of the quality of life. RESULTS: Female patients preferred NUC (p < 0.0001). The pain intensity (4.13 ±1.71 compared to 3.35 ±1.01, p < 0.0001), dyspnea (3.89 ±1.48 compared to 2.82 ±0.97, p < 0.0001), constipation (3.56 ±1.78 compared to 3.06 ±1.89, p = 0.0107), and degree of symptom distress (38.09 ±7.26 compared to 35.05 ±7.92, p = 0.0002) were reported higher among patients from the ONC cohort than among those from the NUC cohort. Patients from the NUC cohort reported a better quality of life than those from the ONC cohort (70.41 ±13.62 compared to 45.63 ±7.94, p < 0.0001). CONCLUSIONS: The NUC results in better clinical outcome measures and higher quality of life than ONC for patients receiving chemotherapy.
Subject(s)
Neoplasms , Oncologists , Humans , Female , Quality of Life , Palliative Care/methods , Retrospective Studies , Nurse's Role , Neoplasms/drug therapy , Surveys and QuestionnairesABSTRACT
Wasp pupa protein has triggered allergies in certain consumers. In this study, we investigated the allergenicity of alcohol-soluble wasp pupa protein (ACWP) and its effect on the gut microbiota of mice in vivo. It was found that ACWP caused skin erythema and diarrhea in mice, the up-regulation of HIS, IgE, IL-4, IL-22, and IL-17A, and down-regulation of IgG2a, IgA, and IL-2 in serum. The results also revealed that the thymus, spleen, and small intestine structures in mice also altered significantly, and the intestinal wall structure was disrupted. Fluorescein isothiocyanate (FITC) labeled dextran intestinal permeability test depicted that the intestinal permeability of mice in the ACWP group increased significantly. The gut microbiota analysis in mice depicted that five bacterial strains in the ACWP group, including s_Candidatus_Arthromitus_sp._SFB_mice_Japa, were up-regulated, and nine low-abundant strains, including s_unclassified_g_norank_f_Ruminococcaceae, were down-regulated. The association analysis of gut microbiota and serum factors showed that eight serum biochemical factors were significantly correlated with 11 strains. The results revealed that ACWP could cause disturbance of gut microbiota and its metabolism, change the integrity and permeability of the intestinal tract, destroy the intestinal mucosal immune system, and then cause skin erythema and diarrhea as the primary manifestations.
Subject(s)
Gastrointestinal Microbiome , Wasps , Allergens/metabolism , Animals , Diarrhea/metabolism , Intestinal Mucosa , Mice , Pupa , Wiskott-Aldrich Syndrome ProteinABSTRACT
Background: China is a country with a high burden of tuberculosis (TB), and students are the high-risk group for TB. The enrollment scale of colleges has increased dramatically due to the advancement of the enrollment expansion system of Chinese colleges. Consequently, this has brought severe challenges to TB prevention and control in colleges. In 2017, a new TB control guide for schools was issued in China, which included the 8 core knowledge of TB. The target of the overall awareness rate on TB among population was "≥85%," which was proposed by the "13th Five-Year" National TB Control Plan in China. The cognition of the 8 core knowledge of TB in the new guide among college students is crucial to achieve this target, but few studies on this have been reported. Based on the abovementioned new situation and the new guide, this study aimed to investigate and analyze the cognition, attitudes, and health education needs on TB among freshmen of a medical college in Guangxi province, and discuss how to optimize TB health education in colleges in China. Methods: A cross-sectional study was conducted among freshmen of a medical college in Guangxi, China. A self-designed questionnaire was used to conduct an on-site questionnaire survey. The data was entered in Epidata 4.4.2.1 and was analyzed using SPSS version 25.0. Including descriptive statistics and t-test, and the criterion for statistically significant difference was p < 0.05. Results: A total of 583 freshmen responded to the survey questionnaires. Regarding cognition about the 5 related knowledge of TB, 551 (94.5%) freshmen knew about the predilection site of TB, while 333 (57.1%), 328 (56.4%), 257 (44.1%), and 201 (34.5%) freshmen knew about the pathogen, the policies about free treatment, the designated hospitals, and the World TB Day, respectively. Regarding cognition on the 8 core knowledge of TB, the overall awareness rate among the freshmen is 73.3%(3,420/4,664); the awareness rate of the knowledge that "guarantee adequate sleep, reasonable diet, and strengthen physical exercise can reduce the incidence of TB" among them was the highest at 88.7% (517/583); and the awareness rate of the knowledge that "coughing or sputum expectoration occurred for more than 2 weeks should be suspected of infecting TB and seeking medical treatment in time" among them was the lowest at 47.5% (277/583). Whether students received health education on TB (T = 4.267, p = 0.000) and whether students heard of TB (T = 3.739, p = 0.000) are the main factors of cognition. Five hundred sixty-two (96.4%) and 565 (96.9%) freshmen were willing to learn and tell others about the knowledge of TB, respectively. Three hundred seventy (63.5%.) freshmen, the highest amount, were willing to accept TB health education in the forms of "website, Weibo, and WeChat." Conclusion: The cognition on the 5 related knowledge of TB among freshmen is unbalanced, and the overall awareness rate of the 8 core knowledge of TB among freshmen still needs to be improved. Freshmen who have not heard of TB and have not received TB health education before enrollment are the key intervention groups. It is recommended that institutions make full use of modern multimedia technology, continuously optimize the health education forms, implement precise policies, and strengthen the theoretical and practical health education on TB from the initial entry of freshmen into colleges.
Subject(s)
Health Knowledge, Attitudes, Practice , Tuberculosis , China/epidemiology , Cross-Sectional Studies , Health Education , Humans , Tuberculosis/epidemiology , Tuberculosis/prevention & controlABSTRACT
Blood pressure variability (BPV) is significantly associated with cardiovascular diseases (CVD) and mortality in hemodialysis patients. However, the relationship between blood pressure and CVD in hemodialysis patients is complex and affected by many factors. The present study aimed to assess the association of long-term predialysis BPV with all-cause mortality and major adverse cardiovascular events (MACE). One thousand seven hundred twenty-seven patients receiving maintenance hemodialysis were recruited in nine hemodialysis centers. Predialysis BPV was assessed over 1-year intervals. Outcomes included all-cause mortality and MACE during follow-up periods. The mean age of the final cohort was 59 years, of which 57% were males. Greater predialysis systolic BPV was associated with an increased risk of all-cause mortality (adjusted hazard ratio, 1.101; 95% confidence intervals 1.064-1.140) and MACE (adjusted hazard ratio, 1.091; 95% confidence intervals 1.059-1.125). Results were similar when systolic BPV was stratified by baseline systolic blood pressure. In conclusion, greater predialysis BPV among hemodialysis patients was associated with all-cause mortality and MACE. Strategies to reduce blood pressure variability might be beneficial for hemodialysis patients.
Subject(s)
Cardiovascular Diseases , Hypertension , Blood Pressure/physiology , Blood Pressure Monitoring, Ambulatory/adverse effects , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Humans , Male , Middle Aged , Renal Dialysis/adverse effects , Risk FactorsABSTRACT
Lactarius volemus Fr. is an edible mushroom widely consumed in China. Polysaccharide is an important nutritional component of L. volemus. This research aimed to isolate the polysaccharide from L. volemus and study its structure and bioactivities. A purified polysaccharide was identified and named as LVF-I whose primary structure was proposed considering the comprehensive results of monosaccharide composition, periodate oxidation-smith degradation, methylation analysis, FT-IR and 1D/2D NMR spectroscopy. Then the immunomodulation of LVF-I and its inhibition effect on H1299 and MCF-7 cells were investigated. Results showed that LVF-I (12,894 Da) contained fucose, mannose, glucose and galactose. It had a backbone consisting of â4)-α-D-Glcp-(1â, â6)-ß-D-Manp-(1â, â6)-α-D-Galp-(1 â and â4)-ß-D-Manp-(1â. And its side chains were branched at C2 of â4)-ß-D-Manp-(1 â by â6)-α-D-Galp-(1â, α-D-Glcp-(1â, α-D-Galp-(1 â and α-L-Fucp-(1â. LVF-I (250-1000 µg/mL) could inhibit the proliferation of H1299 and MCF-7 cells, while enhance the proliferative response of splenocyte and the phagocytic ability of RAW264.7. Furthermore, LVF-I (250-1000 µg/mL) significantly induced the secretion of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by up-regulating their mRNA expression in macrophages. These results suggested that LVF-I had the potential to be developed as antitumor or immunomodulatory agents by inhibiting the proliferation of tumor cells and stimulating macrophages-mediated immune responses.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Basidiomycota/chemistry , Fungal Polysaccharides/chemistry , Fungal Polysaccharides/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/pharmacology , Animals , Antineoplastic Agents/isolation & purification , Cell Line, Tumor , Chemical Phenomena , Cytotoxicity Tests, Immunologic , Fungal Polysaccharides/isolation & purification , Gas Chromatography-Mass Spectrometry , Humans , Immunomodulating Agents/isolation & purification , Magnetic Resonance Spectroscopy , Mice , Molecular Structure , Molecular Weight , RAW 264.7 Cells , Spectroscopy, Fourier Transform Infrared , Structure-Activity RelationshipABSTRACT
BACKGROUND: In peritoneal dialysis (PD) patients, whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could protect residual renal function is still controversial. To assess the effects of ACEIs and ARBs on the residual renal function and cardiovascular (CV) events in peritoneal dialysis patients, we performed a meta-analysis of randomized controlled trials. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library, the CNKI database, and the Wanfang database for relevant articles from database inception to November 30, 2019. Randomized controlled trials were included. The primary outcome was the decline in the residual renal function (RRF). RESULTS: Thirteen trials with 625 participants were included in the meta-analysis. The average residual GFR declined by 1.79 ml/min per 1.73 m2 in the ACEI/ARB group versus 1.44 ml/min per 1.73 m2 in the placebo or active control group at 3 mo. The average residual GFR declined by 2.02 versus 2.06, 2.16 versus 2.72, and -0.04 versus 2.74 ml/min per 1.73 m2 in the placebo or active control group at 6 months (mo), 12 mo, and 24 mo, respectively. The decline in residual GFR showed a significant difference between the ACEI/ARB group and the placebo or active control group at 12 mo (MD = -0.64 ml/min per 1.73 m2; 95% CI: -0.97~-0.32; I 2 = 44%; P < 0.0001). No significant difference was observed in Kt/V, urinary protein excretion, weekly creatinine clearance, CV events, or serum potassium levels. CONCLUSIONS: In the present study, we found that the use of ACEIs and ARBs, especially long-term treatment, decreased the decline of RRF in patients on PD. ACEIs and ARBs do not cause an additional risk of side effects.
Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Glomerular Filtration Rate/drug effects , Peritoneal Dialysis , Adult , Aged , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/pharmacology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Cardiovascular Diseases/epidemiology , Female , Humans , Kidney Diseases/therapy , Male , Middle Aged , Randomized Controlled Trials as TopicABSTRACT
Sepsis accounts for more than 50% of all acute kidney injury (AKI) cases, and the combination of sepsis and AKI increases the risk of mortality from sepsis alone. However, to the best of our knowledge, the specific mechanism by which sepsis causes AKI has not yet been fully elucidated, and there is no targeted therapy for sepsis-associated AKI (SA-AKI). The present study investigated gene expression profiles using RNA sequencing (RNA-Seq) and bioinformatics analyses to assess the function of differentially expressed genes (DEGs) and the molecular mechanisms relevant to the prognosis of SA-AKI. From the bioinformatics analysis, 2,256 downregulated and 3,146 upregulated genes were identified (false discovery rate <0.1 and fold-change >2). Gene Ontology analysis revealed that the genes were enriched in cellular metabolic processes, cell death and apoptosis. The enriched transcription factors were v-rel reticuloendotheliosis viral oncogene homolog A and signaling transducer and activator of transcription 3. The enriched microRNAs (miRNAs or miRs) among the DEGs were miR-30e, miR-181a, miR-340, miR-466d and miR-466l. Furthermore, the enriched pathways included toll-like receptor signaling, nod-like receptor signaling and the Janus kinase/STAT signaling pathway. In conclusion, the present study identified certain prognosis-related genes, transcription factors, miRNAs and pathways by analyzing gene expression profiles of SA-AKI using RNA-Seq, which provides some basis for future experimental studies.
ABSTRACT
BACKGROUND: The aim of this study was to identify the blood potassium level beneficial to the postoperative recovery of gastrointestinal motility during continuous renal replacement therapy (CRRT) in patient undergoing open abdominal surgery. MATERIALS AND METHODS: 538 critically ill patients after open abdominal surgery and receiving CRRT were retrospectively recruited as the study cohort. Demographic and clinical data were recorded along with an evaluation of the postoperative gastrointestinal motility. RESULTS: Correlation analysis was used to assess the correlation coefficient, and then the variables with correlation coefficient value less than 0.5 were included in the binary logistic regression model. Binary logistic regression model indicated that the postoperative blood potassium level was independently associated with the recovery of gastrointestinal motility (OR=0.109, 95% CI= 0.063 to 0.190, p<0.001). Based on the normal range of blood potassium level, we selected the cut-off point of blood potassium level via Weight of Evidence analysis, which was 4.00 mmol/L. Compared with the patients with insufficient blood potassium levels (plasma potassium concentration < 4.00 mmol/L), those with sufficient blood potassium levels (plasma potassium concentration≥ 4.00 mmol/L) conferred an increase in the rate of 4-day postoperative recovery of gastrointestinal motility (OR= 4.425, 95% CI = 2.933 to 6.667, p<0.001). CONCLUSIONS: Maintaining the blood potassium concentrations at a relatively high level of the normal blood potassium range during CRRT would be beneficial to postoperative recovery of gastrointestinal motility.
Subject(s)
Continuous Renal Replacement Therapy , Digestive System Surgical Procedures , Gastrointestinal Motility , Potassium/blood , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of the present study was to determine whether the predialysis serum magnesium level was associated with morbidity of uraemic restless legs syndrome (RLS) in maintenance haemodialysis patients. DESIGN: A retrospective observational study of morbidity of uraemic RLS was conducted. SETTING: Patients on maintenance haemodialysis three times a week. PARTICIPANTS: We reviewed 578 patients receiving maintenance haemodialysis for >1 year as our cohort. OUTCOME MEASURES: Uraemic RLS was diagnosed according to International RLS Study Group criteria, and hypermagnesaemia was defined as serum magnesium level >1.02 mmol/L. RESULTS: The prevalence of uraemic RLS was 14.4% in our study cohort. Univariate analysis indicated that patients with uraemic RLS differed significantly from non-RLS ones in certain demographic and clinical characteristics, including younger age, longer dialysis duration, higher serum parathyroid hormone level and higher prevalence of predialysis hyperphosphataemia and hypermagnesaemia. Binary logistic-regression model analysis indicated that predialysis hypermagnesaemia was independently associated with uraemic RLS and conferred an increase in morbidity of the syndrome (OR=2.024; 95% CI 1.160 to 3.532; p=0.013). Moreover, we found that dialysis duration and predialysis hyperphosphataemia were independently associated with morbidity of uraemic RLS. CONCLUSIONS: Our data indicated that the predialysis serum magnesium level was associated with morbidity of uraemic RLS in maintenance haemodialysis patients and that predialysis hypermagnesaemia might serve as an independent risk factor for the syndrome.
Subject(s)
Magnesium Deficiency/complications , Renal Dialysis/statistics & numerical data , Restless Legs Syndrome/epidemiology , Uremia/complications , Adult , China/epidemiology , Female , Humans , Logistic Models , Magnesium/metabolism , Male , Middle Aged , Prevalence , Restless Legs Syndrome/etiology , Restless Legs Syndrome/metabolism , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: To explore the association between circulating mononuclear cell mitochondrial DNA copy number and the prognosis of sepsis patients based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3 definition). METHODS: A total of 200 adult patients who had recently devoloped sepsis were prospectively recruited as the study cohort. Demographic and clinical data were recorded along with a 28-day outcome. Mononuclear cell mtDNA copy number was assessed by quantitative PCR. RESULTS: The 28-day outcome of sepsis patients was significantly associated with circulating mononuclear cell mtDNA copy number. The median mononuclear cell relative mtDNA copy number of survivors was significantly higher than that of nonsurvivors (406.68, range 196.65-625.35 vs. 320.57, range 175.98-437.33, p = 0.001). The Cox proportional hazard survival model analysis indicated that mononuclear cell relative mtDNA copy number was significantly negative associated with the 28-day outcome. For every additional unit of mononuclear cell mtDNA relative copy number, the risk of death falls by 0.1% (HR = 0.999, 95% CI = 0.998 to 1.000, p = 0.017). CONCLUSIONS: Our data indicate first that circulating mononuclear cellular mtDNA copy number might be helpful for outcome predictions in sepsis patients, and second that lower mtDNA copy number implied poor prognosis.
Subject(s)
Cell-Free Nucleic Acids/blood , DNA, Mitochondrial/blood , Hospital Mortality , Leukocytes, Mononuclear , Sepsis , Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Prospective Studies , Sepsis/blood , Sepsis/mortalityABSTRACT
OBJECTIVE: : To screen genes involved in mitochondrial DNA (mtDNA) damage repair in rats with septic acute kidney injury (SAKI). METHODS: : Forty male C57BL/6J mice were randomly divided into SAKI group (n=28) and sham operation group (n=12). The SAKI mouse model was established by cecal ligation and puncture. Blood and kidney samples were collected at 8, 24, and 48 h after surgery. Serum creatinine and urea nitrogen were measured by a dry biochemical analyzer. Serum inflammatory cytokines were detected by ELISA. Histopathological changes were observed with HE staining. The mtDNA damage repair related genes were screened by RNA sequencing and bioinformatics analysis; the mRNA and protein expression levels of related genes were detected by real-time quantitative RT-PCR and immunohistochemisry, respectively. RESULTS: : Symptoms of sepsis were observed in SAKI group, and 16 out of 28 mice were died in the SAKI group; serum TNF-α, IL-6, creatinine and urea nitrogen levels were higher than those in the sham group (P<0.05 or P<0.01). Histopathological examination in SAKI group showed that renal tubular epithelial cells were swollen, inflammatory cells infiltrated, and a large number of cell vacuoles were seen, suggesting successful modeling. Mitochondrial DNA damage repair related genes Gadd45α, Bcl2l1, Cdkn1a, Jun, Rela, Nfkbia and Nfkb1 were screened out. The expression of these genes was detected by real-time RT-PCR, and the results were consistent with RNA sequencing trends. Immunohistochemical staining showed that Gadd45α was mainly expressed in the nucleus of renal tubular epithelial cells, and the positive rate of Gadd45α in SAKI group was higher than that in the sham operation group (P<0.05). CONCLUSIONS: : Gadd45α, Bcl2l1, Cdkn1a, Jun, Rela, Nfkbia and Nfkb1 genes are involved in mtDNA damage repair in rats with SAKI, indicating that these genes may be used as new targets for prevention and treatment of SAKI.
Subject(s)
Acute Kidney Injury , DNA Repair , DNA, Mitochondrial , Sepsis , Acute Kidney Injury/physiopathology , Animals , Blood Urea Nitrogen , Creatinine/blood , DNA Repair/genetics , Male , Mice , Mice, Inbred C57BL , Random Allocation , Rats , Sepsis/physiopathologyABSTRACT
The 2009 Oxford Classification of immunoglobulin A (IgA) nephropathy (IgAN) identifies four histological features as predictors of renal prognosis: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T). However, the clinical and prognostic significance of crescent formation still remains controversial. Therefore, we performed a meta-analysis to evaluate the association between crescents and kidney outcome in IgAN. A total of 20 studies published from January 2009 to July 2016 involving 5,285 patients were included after systematic searches of PubMed and EMBASE databases. Pooled results showed that crescent lesions were associated with kidney failure (HR, 1.93; 95% CI, 1.49-2.50; P < 0.001). IgAN patients with crescents had lower eGFR levels (SMD, -0.21; 95% CI, -0.40--0.03; P = 0.023); higher proteinuria levels (SMD, 0.87; 95% CI, 0.11-1.63; P = 0.024); a larger number of patients with M1 (RR, 1.22; 95% CI, 1.07-1.40; P = 0.003), E1 (RR, 4.83; 95% CI, 3.04-7.66;P < 0.001), S1 (RR, 1.76; 95% CI, 1.11-2.80; P = 0.016) and T1/2 (RR, 2.74; 95% CI, 2.10-3.57; P < 0.001) lesions; and received immunosuppressive therapy more frequently (RD, 0.17; 95% CI, 0.11-0.23; P < 0.001). Our results suggest that crescent formation represents an efficient prognostic factor associated with progression to kidney failure and thus could be considered into the new Oxford Classification.
Subject(s)
Glomerulonephritis, IGA/diagnosis , Kidney Glomerulus/pathology , Biomarkers , Comorbidity , Disease Progression , Glomerular Filtration Rate , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/epidemiology , Glomerulonephritis, IGA/mortality , Humans , Immunosuppressive Agents/therapeutic use , Odds Ratio , Patient Outcome Assessment , Prognosis , Proportional Hazards Models , Publication BiasABSTRACT
OBJECTIVE: To propose a method for predicting the postoperative anterior chamber depth value (ACD) based on the evaluation standard of contrast sensitivity function (CSF). METHODS: In a personalized eye model, the natural lens was replaced with an artificial lens, and the tracing method based on ZEMAX software was utilized to simulate the pseudophakic optical system. The best MTF curve was obtained through optical optimization to calculate the CSF and determine the best contrast sensitivity (CS) curve. The best ACD value was acquired according to the CSF curve. The data form 10 cataract cases without retinal diseases were obtained and the postoperative ACD value was predicted using Holladay, Hoffer Q, SRK/T and the proposed method. RESULTS: Consistency analysis of the results showed that all the ACD values predicated by the 4 methods fell in 95% consistency within the boundaries, and the differences in the largest absolute value between the 3 methods (Holladay, Hoffer Q, and SRK/T) and the proposed method were 0.73 mm, 0.65 mm, and 0.68 mm, and the calculation results of the mean value were 5.846 mm, 5.804 mm, and 5.825 mm. Clinically, the two methods were deemed to have good consistency. CONCLUSION: The proposed method establishes a connection between the contrast sensitivity curve and ACD to allow better refraction adjustment for the patients.