Worldwide burden and trends of diabetes among people aged 70 years and older, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Diabetes places a significant burden on personal and public health. However, a comprehensive assessment of the burden of diabetes in older adults is lacking. We aimed to estimate the global burden of diabetes and explore trends for the population aged ≥70 from 1990 to 2019. METHODS: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the prevalence, mortality, and disability-adjusted life-years (DALYs) of diabetes among people aged ≥70 were estimated by sex and age group in 2019. We also assessed the epidemiological trend of diabetes from 1990 to 2019. RESULTS: In 2019, 110.1 million (95% uncertainty interval [UI]: 101.2-119.4) people aged ≥70 years were living with diabetes (types 1 and 2 combined) with a global prevalence of 23.7% (21.8%-25.8%). Worldwide, 181.9 deaths (163.0-194.7) per 100,000 population and 4512.3 DALYs (3861.3-5264.2) per 100,000 population occurred due to diabetes. In 2019, minor sex-related disparities in the burden of diabetes were identified among specific age and sex groups. From 1990 to 2019, the prevalence of diabetes increased by 39.7% (37.7%-41.7%), and the related mortality and DALY rates also increased (16.4% [9.43%-22.9%] and 22.3% [17.2%-27.0%], respectively). CONCLUSION AND RELEVANCE: The global burden of diabetes in adults aged ≥70 has increased markedly from 1990 to 2019. As the population continues to age, there is an urgent need to combat the increasing disease burden.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

Prevalence and prognosis of malignancy in THSD7A-associated membranous nephropathy: a systematic literature review and clinical case study.

BACKGROUND: This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN). METHODS: First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3-5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy. RESULTS: We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9-17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer. CONCLUSIONS: Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.

Cascade Cyclization of 1,5-Diynols and (RO)2P(O)SH to Construct Benzo[b]fluorenyl S-Alkyl Phosphorothioates under Catalyst-Free Conditions.

An efficient and practical cascade cyclization of 1,5-diynols with (RO)2P(O)SH as the acid promoter and nucleophile under mild conditions was developed. A variety of highly substituted benzo[b]fluorenyl-containing S-alkyl phosphorothioates were successfully constructed in moderate to excellent yields. Furthermore, this protocol exhibited good functional group tolerance, a broad substrate scope, and potential practical applications, with water as the only byproduct. The reaction proceeded with allenyl thiophosphate as a key intermediate, followed by a Schmittel-type cyclization process to produce the target product.

Protein restriction for diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) continues to be the leading cause of kidney failure across the world. For decades dietary protein restriction has been proposed for patients with DKD with the aim to retard the progression of chronic kidney disease (CKD) towards kidney failure. However, the relative benefits and harms of dietary protein restriction for slowing the progression of DKD have not been addressed. OBJECTIVES: To determine the efficacy and safety of low protein diets (LPD) (0.6 to 0.8 g/kg/day) in preventing the progression of CKD towards kidney failure and in reducing the incidence of kidney failure and death (any cause) in adult patients with DKD. Moreover, the effect of LPD on adverse events (e.g. malnutrition, hyperglycaemic events, or health-related quality of life (HRQoL)) and compliance were also evaluated. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which adults with DKD not on dialysis were randomised to receive either a LPD (0.6 to 0.8 g/kg/day) or a usual or unrestricted protein diet (UPD) (≥ 1.0 g/kg/day) for at least 12 months. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies and extracted data. Summary estimates of effect were obtained using a random-effects model. Results were summarised as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised MD (SMD) with 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified eight studies involving 486 participants with DKD. The prescribed protein intake in the intervention groups ranged from 0.6 to 0.8 g/kg/day. The prescribed protein intake in the control groups was ≥ 1.0 g/kg/day, or a calculated protein intake ≥ 1.0 g/kg/day if data on prescribed protein intake were not provided. The mean duration of the interventions was two years (ranging from one to five years). Risks of bias in most of the included studies were high or unclear, most notably for allocation concealment, performance and detection bias. All studies were considered to be at high risk for performance bias due to the nature of the interventions. Most studies were not designed to examine death or kidney failure. In low certainty evidence, a LPD may have little or no effect on death (5 studies, 358 participants: RR 0.38, 95% CI 0.10 to 1.44; I² = 0%), and the number of participants who reached kidney failure (4 studies, 287 participants: RR 1.16, 95% CI 0.38 to 3.59; I² = 0%). Compared to a usual or unrestricted protein intake, it remains uncertain whether a LPD slows the decline of glomerular filtration rate over time (7 studies, 367 participants: MD -0.73 mL/min/1.73 m²/year, 95% CI -2.3 to 0.83; I² = 53%; very low certainty evidence). It is also uncertain whether the restriction of dietary protein intake impacts on the annual decline in creatinine clearance (3 studies, 203 participants: MD -2.39 mL/min/year, 95% CI -5.87 to 1.08; I² = 53%). There was only one study reporting 24-hour urinary protein excretion. In very low certainty evidence, a LPD had uncertain effects on the annual change in proteinuria (1 study, 80 participants: MD 0.90 g/24 hours, 95% CI 0.49 to 1.31). There was no evidence of malnutrition in seven studies, while one study noted this condition in the LPD group. Participant compliance with a LPD was unsatisfactory in nearly half of the studies. One study reported LPD had no effect on HRQoL. No studies reported hyperglycaemic events. AUTHORS' CONCLUSIONS: Dietary protein restriction has uncertain effects on changes in kidney function over time. However, it may make little difference to the risk of death and kidney failure. Questions remain about protein intake levels and compliance with protein-restricted diets. There are limited data on HRQoL and adverse effects such as nutritional measures and hyperglycaemic events. Large-scale pragmatic RCTs with sufficient follow-up are required for different stages of CKD.

A back propagation neural network approach to estimate the glomerular filtration rate in an older population.

BACKGROUND: The use of creatinine-based glomerular filtration rate (GFR)-estimating equations to evaluate kidney function in elderly individuals does not appear to offer any performance advantages. We therefore aimed to develop an accurate GFR-estimating tool for this age group. METHODS: Adults aged ≥ 65 years who underwent GFR measurement by technetium-99 m-diethylene triamine pentaacetic acid (99mTc-DTPA) renal dynamic imaging were included. Data were randomly split into a training set containing 80% of the participants and a test set containing the remaining 20% of the subjects. The Back propagation neural network (BPNN) approach was used to derive a novel GFR estimation tool; then we compared the performance of the BPNN tool with six creatinine-based equations (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], Berlin Initiative Study-1 [BIS1], Lund-Malmö Revised [LMR], Asian modified CKD-EPI, and Modification of Diet in Renal Disease [MDRD]) in the test cohort. Three equation performance criteria were considered: bias (difference between measured GFR and estimated GFR), precision (interquartile range [IQR] of the median difference), and accuracy P30 (percentage of GFR estimates that are within 30% of measured GFR). RESULTS: The study included 1,222 older adults. The mean age of both the training cohort (n = 978) and the test cohort (n = 244) was 72 ± 6 years, with 544 (55.6%) and 129 (52.9%) males, respectively. The median bias of BPNN was 2.06 ml/min/1.73 m2, which was smaller than that of LMR (4.59 ml/min/1.73 m2; p = 0.03), and higher than that of the Asian modified CKD-EPI (-1.43 ml/min/1.73 m2; p = 0.02). The median bias between BPNN and each of CKD-EPI (2.19 ml/min/1.73 m2; p = 0.31), EKFC (-1.41 ml/min/1.73 m2; p = 0.26), BIS1 (0.64 ml/min/1.73 m2; p = 0.99), and MDRD (1.11 ml/min/1.73 m2; p = 0.45) was not significant. However, the BPNN had the highest precision IQR (14.31 ml/min/1.73 m2) and the greatest accuracy P30 among all equations (78.28%). At measured GFR < 45 ml/min/1.73 m2, the BPNN has highest accuracy P30 (70.69%), and highest precision IQR (12.46 ml/min/1.73 m2). The biases of BPNN and BIS1 equations were similar (0.74 [-1.55-2.78] and 0.24 [-2.58-1.61], respectively), smaller than any other equation. CONCLUSIONS: The novel BPNN tool is more accurate than the currently available creatinine-based GFR estimation equations in an older population and could be recommended for routine clinical use.

Crescents proportions above 10% are associated with unfavorable kidney outcomes in IgA nephropathy patients with partial crescent formation.

PURPOSE: Whether different crescentic proportions determine the progression of IgA nephropathy (IgAN) with crescents in less than 50% of glomeruli remains controversial. We aimed to evaluate the relationship between different proportions of crescents and kidney outcomes in IgAN with partial crescent formation. METHODS: Patients diagnosed as IgAN, having at least two crescents and in less than 50% of glomeruli, were categorized into three groups: Group I (crescents in ≤10% of glomeruli), Group II (10%< crescents ≤25% of glomeruli) and Group III (crescents >25% of glomeruli). Baseline clinicopathological parameters were evaluated. The kidney endpoint was a composite of a ≥ 40% decline in the initial estimated glomerular filtration rate, end-stage kidney disease, and kidney disease-related death. RESULTS: Of 183 IgAN patients with crescents in less than 50% of glomeruli, baseline 24-hour urinary protein and immunosuppressive treatment varied among the three groups (p < 0.05). During a median follow-up of 57 months (interquartile range 28-86), 50 (27.3%) patients reached the composite outcome. Kaplan-Meier survival analysis revealed that kidney survival in Group II (p = 0.049) and Group III (p = 0.008) was significantly shorter than in Group I, with no significant difference between Group II and III (p = 0.2). After adjusting for clinical factors and MEST score based on the multivariate Cox regression analysis, a crescent proportion >10% (HR = 3.431, 95% CI 1.067-11.03, p = 0.039) was predictive of time to unfavorable kidney outcome, with model adjustments improving predictability (c-index: 0.817). CONCLUSION: The proportion of crescents reaching 10% of glomeruli in IgAN was identified as an independent risk factor for kidney survival.

ERK Modulates Macrophage Polarization and Alters Exosome miRNA Expression in Diabetic Nephropathy.

BACKGROUND: The aim is to probe into the differential expression of miRNA in macrophage exosomes in diabetic nephropathy (DN) by ERK regulating macrophage polarization through the NF-κB/JAK-STAT signaling pathway. METHODS: Our team cultivated the mouse macrophage line RAW264 cells. When the cell growth status was good, we added 30 mmol/L glucose, and then added ERK/JAK-STAT/NF-κB inhibitors separately. We adopted western blot for observing macrophage polarization and the impact of JAK-STAT inhibitor on caspase-9, eNOS, NF-κB p65 expression, extracted exosomes, and total exosome RNA of each group of cells. Their miRNA expression profiles were also analyzed by high-throughput sequencing. RESULTS: (1) In comparison with the control group, relative iNOS protein expression in ERK inhibitor group dramatically declined (p < 0.05), and the iNOS protein content in the NF-κB inhibitor group and the JAK-STAT inhibitor group conspicuously dwindled (p < 0.05); relative CD206 protein expression in each inhibitor group was clearly augmented (p > 0.05). Under the intervention of high glucose, ERK/JAK-STAT/NF-κB inhibitors brilliantly diminished the up-regulation of caspase-9 (p < 0.05), and ERK/JAK-STAT inhibitors notably minimized the up-regulation of NF-κB p65 (p < 0.05). ELISA results unveiled that in contrast to the control group, TNF-α, IL-1ß, and CXCL10 levels in the macrophage supernatant of the inhibitor group was tellingly augmented (p < 0.05), whereas TGF-ß level had strikingly declined (p < 0.05), proving that macrophages were activated to M1. (2) Flow cytometry uncloaked that the phagocytic ability of macrophages in inhibitor group was compellingly lower than that in the control group. (3) One hundred thirty-six known miRNAs with notably differential expression and 5,134 miRNA sequences were detected in the exosomes of the macrophage supernatant of each experimental group. Of those, some differentially expressed miRNAs include miR-193a-3p, miR-1260B, and miR-3175. miR-193a-3p, miR-1260B, and miR-3175 extensively participate in the development of cancer, arthritis, osteogenic differentiation, Alzheimer's disease, and other diseases, as well as in the regulation of MAPK/ERK, TLR4/NF-κB, and other signaling pathways. CONCLUSIONS: ERK modulates macrophage activation to M1 and alters exosome miRNA expression profile via NF-κB/JAK-STAT pathway.

Glial cell line-derived neurotrophic factor alters lipid composition and protein distribution in MPP+-injured differentiated SH-SY5Y cells.

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and striatum. Glial cell line-derived neurotrophic factor (GDNF) can effectively promote the differentiation and survival of many types of neurons, especially dopaminergic neurons, suggesting it could be a treatment for PD. Lipid rafts are highly dynamic cell membrane domains that contain numerous signal protein receptors, providing an important platform for signal transduction. Compelling evidence indicates that alterations in lipid rafts are associated with PD, and some studies have reported that GDNF can regulate the expression of caveolin-1, a lipid raft-marker protein. However, the precise effects of GDNF on lipid rafts remain unknown. We developed a cellular PD model, purified detergent-resistant membranes (membrane rafts), and performed proteomic and lipid metabolomics analyses to examine changes in lipid rafts after GDNF treatment. The results showed considerable protein and lipid alterations in response to GDNF, especially altered levels of dopamine-ß-hydroxylase, heat shock 70 kDa protein, neural cell adhesion molecule, cytoskeletal proteins, and long-chain polysaturated/unsaturated fatty acids. These findings reveal a new avenue to explore the relationships between GDNF, lipid rafts, and PD and support the hypothesis that GDNF may be a useful treatment for PD.

Intrinsically reducing divergence angle of Cherenkov radiation from dielectric capillary.

Narrow-band terahertz (THz) Cherenkov radiation can be excited as a relativistic electron bunch passes through the dielectric capillary with sub-millimeter radius. However, due to the diffraction effect, the radiation will enter free space with a large divergence angle, which makes it difficult to collect the radiation energy efficiently. In this Letter, to deal with this challenge, we propose to add a new dielectric layer, which satisfies a special relationship with the electron velocity, between the metal coating and original dielectric layer in the capillary. According to numerical simulation and theoretical analysis results, the divergence angle of radiation is significantly suppressed, and the peak power density is also enhanced by over two orders. As a result, the transmission efficiency from the radiation source to the optical system can be increased to over 90%. We expect that this method will provide a new way to generate THz Cherenkov radiation.

Chirp control of tunable terahertz synchrotron radiation.

It is of scientific significance to explore the terahertz radiation source with the performances of high power, tunable frequency, and controllable chirp for the realization of coherent control of quantum systems. How to realize frequency chirp control of terahertz synchrotron radiation is the last puzzle to be completed. In this Letter, we propose a method to control the radiation frequency chirp with precision. A novel photomixing scheme is presented to generate a longitudinally modulated laser pulse with non-uniform time intervals between the adjacent micro-peaks, which means that there is a chirp in the modulation frequency, and this chirp can be continuously tuned. The interaction is made to occur between an electron beam and the modulated laser pulse in a modulator (an undulator tuned at the laser wavelength), then terahertz synchrotron radiation with the same spectrum characteristics as the modulated laser will be generated when the electron beam passes through the following bending magnet. We expect that this method will open a new way for the coherent control of quantum systems in the terahertz regime.

Novel Model Predicts Diabetic Nephropathy in Type 2 Diabetes.

BACKGROUND: Clinical indicators for accurately distinguishing diabetic nephropathy (DN) from non-diabetic renal disease in type 2 diabetes (T2D) are lacking. This study aimed to develop and validate a nomogram for predicting DN in T2D patients with kidney disease. METHODS: A total of 302 consecutive patients with T2D who underwent renal biopsy at China-Japan Friendship Hospital between January 2014 and June 2019 were included in the study. The data were randomly split into a training set containing 70% of the patients (n = 214) and a validation set containing the remaining 30% of patients (n = 88). Multivariable logistic regression analyses were applied to develop a prediction nomogram incorporating the candidates selected in the least absolute shrinkage and selection operator regression model. Discrimination, calibration, and clinical usefulness of the prediction model were assessed using a concordance index (C-index), calibration plot, and decision curve analysis. Both internal and external validations were assessed. RESULTS: A multivariable model that included gender, diabetes duration, diabetic retinopathy, hematuria, glycated hemoglobin A1c, anemia, blood pressure, urinary protein excretion, and estimated glomerular filtration rate was represented as the nomogram. The model demonstrated very good discrimination with a C-index of 0.934 (95% CI 0.904-0.964). The calibration plot diagram of predicted probabilities against observed DN rates indicated excellent concordance. The C-index value was 0.91 for internal validation and 0.875 for external validation. Decision curve analysis demonstrated that the novel nomogram was clinically useful. CONCLUSION: The novel model was very useful for predicting DN in patients with T2D and kidney disease, and thereby could be used by clinicians either in triage or as a replacement for biopsy.

Generating three-color pulses in high-gain harmonic-generation free-electron lasers with a tilted electron bunch.

A multi-color light source is a significant tool for nonlinear optics experiments, pump-dump/repump-probe experiments and in other fields. Here, a novel method is proposed to create three-color pulses based on a high-gain harmonic-generation (HGHG) free-electron laser with a tilted electron bunch. In this method, the initial bunch tilt is created by transverse wakefields after the bunch passes through a corrugated structure with an off-axis orbit, and is further enlarged in a following drift section. Then the tilted bunch experiences the off-axis field of a quadrupole magnet to cool down the large transverse velocity induced before. After that, it enters an HGHG configuration adopting a transverse gradient undulator (TGU) as the radiator, where only three separated fractions of the tilted bunch will resonate at three adjacent harmonics of the seed wavelength and are enabled to emit three-color pulses simultaneously. In addition, the use of the natural transverse gradient of a normal planar undulator instead of the TGU radiator to emit three-color pulses is also studied in detail. Numerical simulations including the generation of the tilted bunch and the free-electron laser radiation confirm the validity and feasibility of this scheme both for the TGU radiator and the natural gradient in the extreme-ultraviolet waveband.

Expression of the intrarenal angiotensin receptor and the role of renin-angiotensin system inhibitors in IgA nephropathy.

The critical role of the intrarenal renin-angiotensin system (RAS) in the development of kidney disease has been well demonstrated in animal and cell-culture experiments, but evidence from human kidney tissues is lacking. In this study, we screened 438 patients with IgA nephropathy (IgAN) and analyzed their clinical characteristics. Renal biopsy revealed the expression of angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), and MAS receptor (MASR) in the tissues of 260 patients not treated with RAS inhibitors, 32 patients treated with angiotensin-converting enzyme inhibitors (ACEIs), and 89 patients treated with angiotensin receptor blockers (ARBs). The correlations in expression among these three receptors and the results of Oxford typing were analyzed, together with the ability of ACEIs and ARBs to reduce proteinuria and the effects of ARBs on AT1R and AT2R expression. The results showed significantly higher AT1R, AT2R, and MASR expression in the M1 group (mesangial score > 0.5) than in the M0 group (mesangial score < 0.5), significantly higher AT1R expression in the S1 group (presence of segmental glomerulosclerosis) than in the S0 group (absence of segmental glomerulosclerosis); AT1R expression in the C2 group (crescent formation > 25%) was significantly higher than in the C0 (crescent formation = 0) and C1 (crescent formation < 25%) groups. Patients treated with an ARB for < 6 months had significantly lower urinary protein levels than those taking these drugs for > 6 months. These findings imply that overexpression of AT1R on the mesangial cells of IgAN patients is associated with mesangial cell proliferation, glomerular segmental sclerosis, and crescent formation. In addition, long-term administration of ARB may decrease the efficacy of these medications in terms of reducing proteinuria.

Efficacy and safety of immunosuppressive treatment in IgA nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUND: Immunosuppressive agents have been widely used in the treatment of IgA nephropathy (IgAN), but the efficacy and safety remain controversial. The recent STOP-IgAN and TESTING studies have again focused attention on the application of immunosuppressive agents in IgAN. This study investigated the benefits and risks of immunosuppressive agents in IgAN. METHODS: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), and adverse events in patients with IgAN, and trial sequential analyses were also performed for outcomes. RESULTS: Twenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. Steroids (weighted mean difference [WMD] -0.70, 95% confidence interval [CI] -1.2 to - 0.20), non-steroidal immunosuppressive agents (NSI) (WMD -0. 43, 95% CI - 0.55 to - 0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) (WMD -1.46, 95% CI - 2.13 to - 0.79) therapy significantly reduced proteinuria levels compared with the the control group. Steroid treatment significantly reduced the risk of end-stage renal disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79) compared with the control group. The immunosuppressive therapy group showed significant increases in gastrointestinal, hematological, dermatological, and genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia was more common in the control group. CONCLUSION: Immunosuppressive therapy can significantly reduce proteinuria and ESRD risk in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care is required in the application of immunosuppressive agents in IgAN.

Diagnostic Performance of Retinopathy in the Detection of Diabetic Nephropathy in Type 2 Diabetes: A Systematic Review and Meta-Analysis of 45 Studies.

AIMS: To conduct an evidence-based evaluation of diabetic retinopathy (DR) for the diagnosis of diabetic nephropathy (DN) in type 2 diabetics with kidney disease. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library from inception to June 27, 2018, including the reference lists of identified primary studies. A study was included if it (1) used DR as a diagnostic test for DN; and (2) used histological evaluation of renal tissues as the reference standard. RESULTS: The analysis included 45 studies (4,561 patients). A bivariate analysis yielded a sensitivity of 0.67 (95% CI 0.61-0.74) and a specificity of 0.78 (95% CI 0.73-0.82). The summary receiver operating characteristic curve analysis provided an area under the curve (AUC) of 0.79 (95% CI 0.76-0.83). In a setting of 41% prevalence of DN, the probability of DN would be 68% if the test of DR was positive, and the probability of DN would be 23% if it was negative. In addition, although the mean specificity of proliferative DR for the detection of DN was 0.99 (95% CI 0.45-1.00), the mean sensitivity was 0.34 (95% CI 0.24-0.44), and the AUC was 0.58 (95% CI 0.53-0.62). CONCLUSIONS: DR is helpful in diagnosing DN in persons with type 2 diabetes and kidney disease, but the severity of DR may not parallel the presence of DN.

Novel actin filaments from Bacillus thuringiensis form nanotubules for plasmid DNA segregation.

Here we report the discovery of a bacterial DNA-segregating actin-like protein (BtParM) from Bacillus thuringiensis, which forms novel antiparallel, two-stranded, supercoiled, nonpolar helical filaments, as determined by electron microscopy. The BtParM filament features of supercoiling and forming antiparallel double-strands are unique within the actin fold superfamily, and entirely different to the straight, double-stranded, polar helical filaments of all other known ParMs and of eukaryotic F-actin. The BtParM polymers show dynamic assembly and subsequent disassembly in the presence of ATP. BtParR, the DNA-BtParM linking protein, stimulated ATP hydrolysis/phosphate release by BtParM and paired two supercoiled BtParM filaments to form a cylinder, comprised of four strands with inner and outer diameters of 57 Å and 145 Å, respectively. Thus, in this prokaryote, the actin fold has evolved to produce a filament system with comparable features to the eukaryotic chromosome-segregating microtubule.

The correlation between peripheral leukocyte telomere length and indicators of cardiovascular aging.

OBJECTIVES: To investigate the relationship between telomere length in peripheral blood white cells and cardiovascular function in a healthy, aging Han Chinese population. METHODS: In 2012, peripheral blood leukocytes were obtained from 139 healthy individuals in Beijing, China, and telomere restriction fragment (TRF) length was assayed using a digoxigenin-labeled hybridization probe in Southern blot assays. Indicators of cardiovascular function were also evaluated, including electrocardiograms (ECG), (RR, P, PR, QRS, ST and T intervals); blood pressure (BP), (SBP, DBP, PP, PPI); cardiovascular ultrasound (left ventricular ejection fraction, LVEF); mitral early and late diastolic peak flow velocity (MVE and MVA); and lipid indices (TC, TG, HDL, LDL, LCI). The relationships of these cardiovascular indictors to telomere length were evaluated. RESULTS: No correlations were found between telomere length and ECG, BP or lipid indices even after adjustment for age. Correlations were found between TFR length and some cardiovascular ultrasound indictors (D, MVEA, MVEDT, MVES, MVEL, MVEI, IMT), but these were not seen after adjusting for age. CONCLUSIONS: We did not find that leukocyte TFR length was associated with cardiovascular ultrasound indictors, ECG, BP, or lipid indices in this population of healthy Han Chinese individuals. Telomere length may serve as a genetic factor in biological aging.

Effects of finerenone and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus: a systematic review and meta-analysis.

OBJECTIVE: To assess the effects of finerenone and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), and the relative cardiovascular benefits in patients with or without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs. METHODS: We searched PubMed, the Cochrane Library, and Embase from January 1, 2000, to December 30, 2022, to identify randomized controlled trials. The primary outcomes were the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and a composite of renal outcomes. The results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In total, we identified 11 trials and 73,927 participants, 13,847 (18.7%) in finerenone trials and 60,080 (81.3%) in GLP1-RA trials. Finerenone reduced the risk of MACE by 13% (HR, 0.87; 95% CI, 0.79-0.95; P = 0.003), while GLP1-RA reduced the risk in a similar magnitude by 13% (HR, 0.87; 95% CI, 0.83-0.92; P < 0.001). For both drug classes, the effect on lowering the risk of MACE was restricted to approximately 14% in patients with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.82-0.90; P < 0.001), whereas no effect was observed in patients without established atherosclerotic cardiovascular disease (HR, 0.93; 95% CI, 0.85-1.02; P = 0.12). GLP1-RA reduced myocardial infarction, stroke and cardiovascular death more than finerenone (which appeared to have no effect). Only finerenone was beneficial for reducing the risk of HHF (HR, 0.78; 95% CI, 0.66-0.92; P = 0.003). Both finerenone (HR, 0.84; 95% CI, 0.77-0.92; P < 0.001) and GLP1-RA (HR, 0.81; 95% CI, 0.76-0.86; P < 0.001) reduced the risk of kidney disease progression, including macroalbuminuria, and finerenone was superior to GLP1-RA in delaying deterioration of kidney function. CONCLUSIONS: Finerenone and GLP1-RA lead to a risk reduction in MACE to a similar degree in patients with established atherosclerotic cardiovascular disease. For both drug classes, the effect on lowering the risk of progression of kidney disease was also in a similar magnitude in patients with T2DM, whereas only finerenone had a significant protective effect against HHF. Treatment decisions for patients with T2DM should consider the clinical benefit profiles of each drug.