Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells.

Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

Comparison of different peritoneal dialysis catheters on complication and catheter survival: A network meta-analysis of randomised controlled trials.

BACKGROUND: This network meta-analysis (NMA) aimed to compare the clinical advantage of four commonly used peritoneal dialysis catheters (PDCs) including the Swan neck segment with straight tip (Swan neck + S), Tenckhoff segment with straight tip (Tenckhoff + S), Swan neck segment with coiled tip (Swan neck + C) and Tenckhoff segment with coiled tip (Tenckhoff + C). METHODS: Randomised clinical trials were searched from PubMed, Embase, the Cochrane Register of clinical trials, China National Knowledge Infrastructure (CNKI) and ChinaInfo from their inception until July 31, 2022. Meta-analysis was performed using Stata 14.0 and RevMan 5.3.5 software to evaluate the four commonly used PDCs. RESULTS: Seventeen studies involved 1578 participants were included. NMA showed that compared with Swan neck + C, Swan neck + S significantly reduced catheter tip migration (OR 0.47 95% CI 0.22-0.99). Tenckhoff + S was more effective in reducing catheter dysfunction (OR 0.42, 95% CI 0.23-0.79), catheter tip migration with dysfunction (OR 0.19, 95% CI 0.05-0.78) and catheter removal (OR 0.56, 95% CI 0.34-0.93) which were consistent with the pairwise meta-analysis. According to the surface under the cumulative ranking curve, Swan neck + S emerged as the best PDC in the reduction of catheter tip migration (83.3%), followed by Tenckhoff + S (79.4%). Moreover, Tenckhoff + S (86.5%, 76.3%) and Swan neck + S (72.3, 86.9%) ranked as the first and second PDC for 1 and 2-year technique survival which was significantly higher than those of the other two PDCs. CONCLUSION: Our NMA showed Swan neck + S and Tenckhoff + S tended to be more efficacious than Swan neck + C and Tenckhoff + C in lowering the mechanical dysfunction and prolonging the technique survival, which may contribute to better clinical decisions. More randomised controlled trials with larger scales and higher quality are needed in order to obtain more credible evidence.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Solvent-controlled halohydroxylation or C3-C2 coupling of pyridinium salts through an interrupted dearomative reduction.

Herein, we report an efficient and easily operable method to halohydroxylate pyridiniums through an interrupted dearomative reduction strategy. In this process, we make the most of the halide anion from the pyridinium salts by performing the reaction in DMSO without the need of external HX added. Notably, by changing the solvents from DMSO into Et2O, the bimolecular C3-C2 coupling occurs successfully.

The protective mechanism of SIRT3 and potential therapy in acute kidney injury.

Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

Transient Dynamic Operation of G-Quadruplex-Gated Glucose Oxidase-Loaded ZIF-90 Metal-Organic Framework Nanoparticle Bioreactors.

Glucose oxidase-loaded ZIF-90 metal-organic framework nanoparticles conjugated to hemin-G-quadruplexes act as functional bioreactor hybrids operating transient dissipative biocatalytic cascaded transformations consisting of the glucose-driven H2O2-mediated oxidation of Amplex-Red to resorufin or the glucose-driven generation of chemiluminescence by the H2O2-mediated oxidation of luminol. One system involves the fueled activation of a reaction module leading to the temporal formation and depletion of the bioreactor conjugate operating the nickase-guided transient biocatalytic cascades. The second system demonstrates the fueled activation of a reaction module yielding a bioreactor conjugate operating the exonuclease III-dictated transient operation of the two biocatalytic cascades. The temporal operations of the bioreactor circuits are accompanied by kinetic models and computational simulations enabling us to predict the dynamic behavior of the systems subjected to different auxiliary conditions.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

Nucleic acid-functionalized nanozymes and their applications.

Nanozymes are inorganic, organic and metal-organic framework nanoparticles that reveal catalytic functions by emulating native enzyme activities. Recently, these nanozymes have attracted growing scientific interest, finding diverse analytical and medical applications. However, the catalytic activities and functions of nanozymes are limited, due to the lack of substrate binding sites that concentrate on the substrate at the catalytic site (molarity effect), introduce substrate specificity and allow functional complexity of the catalysts (cascaded, switchable and cooperative catalysis). The modification of nanozymes with functional nucleic acids provides means to overcome these limitations and engineer nucleic acid/nanozyme hybrids for diverse applications. This is exemplified with the synthesis of aptananozymes, which are supramolecular aptamer-modified nanozymes. Aptananozymes exhibit combined specific binding and catalytic properties that drive diverse chemical transformations, revealing enhanced catalytic activities, as compared to the separated nanozyme/aptamer constituents. Relationships of structure-catalytic functions in the aptananozyme constructs are demonstrated. In addition, modification of nanozymes exhibiting multimodal catalytic functions with aptamers allows the engineering of nanozyme-based bioreactors for cascaded catalysis. Also, the functionalization of reactive oxygen species (ROS)-generating nanozymes with cancer cell-recognizing aptamers yields aptananozymes for targeted chemodynamic treatment of cancer cells and cancer tumors elicited in mice. Finally, nucleic acid-modified enzyme (glucose oxidase)-loaded metal-organic framework nanoparticles yield switchable biocatalytic nanozymes that drive the ON/OFF biocatalyzed oxidation of Amplex Red, dopamine or the generation of chemiluminescence. Herein, future challenges of the topic are addressed.

Diagnostic accuracy of the 3-minute diagnostic interview for confusion assessment method-defined delirium in delirium detection: a systematic review and meta-analysis.

BACKGROUND: Delirium is a common complication clinically and is associated with the poor outcomes, yet it is frequently unrecognised and readily disregarded. Although the 3-minute diagnostic interview for confusion assessment method-defined delirium (3D-CAM) has been used in a variety of care settings, a comprehensive evaluation of its accuracy in all available care settings has not been performed. OBJECTIVE: This study aimed to evaluate the diagnostic test accuracy of the 3D-CAM in delirium detection through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL (EBSCO) and ClinicalTrials.gov published from inception to 10 July 2022. The quality assessment of the diagnostic accuracy studies-2 tool was applied to evaluate methodological quality. A bivariate random effects model was used to pool sensitivity and specificity. RESULTS: Seven studies with 1,350 participants and 2,499 assessments were included, which were carried out in general medical wards, intensive care units, internal medical wards, surgical wards, recovery rooms and post-anaesthesia care units. The prevalence of delirium ranged from 9.1% to 25%. The pooled sensitivity and specificity were 0.92 (95% confidence interval [CI] 0.87-0.95) and 0.95 (95% CI 0.92-0.97), respectively. The pooled positive likelihood ratio was 18.6 (95% CI 12.2-28.2), the negative likelihood ratio was 0.09 (95% CI 0.06-0.14) and the diagnostic odds ratio was 211 (95% CI 128-349). Moreover, the area under the curve was 0.97 (95% CI 0.95-0.98). CONCLUSIONS: The 3D-CAM has good diagnostic accuracy for delirium detection in different care settings. Further analyses illustrated that it had comparable diagnostic accuracy in older adults and patients with dementia or known baseline cognitive impairment. In conclusion, the 3D-CAM is recommended for clinical delirium detection.

Distribution of pathological types and epidemiological characteristics based on kidney biopsy in Northwest China.

BACKGROUND: The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. METHODS: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. RESULTS: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. CONCLUSION: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

[Retrospective Analysis of the Effect of Uric Acid on the Prognosis of Immunoglobulin A Nephropathy With Stage 3-4 Chronic Kidney Disease]. / å°¿é ¸æ°´å¹³å¯¹æ ¢æ€§è‚¾è„ç— 3-4期IgAè‚¾ç— é¢„åŽå½±å“çš„å›žé¡¾æ€§åˆ†æž.

Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.

Aptamer-Functionalized Ce4+-Ion-Modified C-Dots: Peroxidase Mimicking Aptananozymes for the Oxidation of Dopamine and Cytotoxic Effects toward Cancer Cells.

Aptamer-functionalized Ce4+-ion-modified C-dots act as catalytic hybrid systems, aptananozymes, catalyzing the H2O2 oxidation of dopamine. A series of aptananozymes functionalized with different configurations of the dopamine binding aptamer, DBA, are introduced. All aptananozymes reveal substantially enhanced catalytic activities as compared to the separated Ce4+-ion-modified C-dots and aptamer constituents, and structure-catalytic functions between the structure and binding modes of the aptamers linked to the C-dots are demonstrated. The enhanced catalytic functions of the aptananozymes are attributed to the aptamer-induced concentration of the reaction substrates in spatial proximity to the Ce4+-ion-modified C-dots catalytic sites. The oxidation processes driven by the Ce4+-ion-modified C-dots involve the formation of reactive oxygen species (•OH radicals). Accordingly, Ce4+-ion-modified C-dots with the AS1411 aptamer or MUC1 aptamer, recognizing specific biomarkers associated with cancer cells, are employed as targeted catalytic agents for chemodynamic treatment of cancer cells. Treatment of MDA-MB-231 breast cancer cells and MCF-10A epithelial breast cells, as control, with the AS1411 aptamer- or MUC1 aptamer-modified Ce4+-ion-modified C-dots reveals selective cytotoxicity toward the cancer cells. In vivo experiments reveal that the aptamer-functionalized nanoparticles inhibit MDA-MB-231 tumor growth.

Prediction of outcomes by diffusion kurtosis imaging in patients with large (≥5 cm) hepatocellular carcinoma after liver resection: A retrospective study.

Purpose: To evaluate preoperative diffusion kurtosis imaging (DKI) in predicting the outcomes of large hepatocellular carcinoma (HCC) after liver resection (LR). Materials and methods: From January 2015 to December 2017, patients with a large (≥5cm) HCC who underwent preoperative DKI were retrospectively reviewed. The correlations of the mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) with microvascular invasion (MVI) or histological grade were analyzed. Cox regression analyses were performed to identify the predictors of recurrence-free survival (RFS) and overall survival (OS). A nomogram to predict RFS was established. P<0.05 was considered as statistically significant. Results: A total of 97 patients (59 males and 38 females, 56.0 ± 10.9 years) were included in this study. The MK, MD, and ADC values were correlated with MVI or histological grade (P<0.01). With a median follow-up time of 41.2 months (range 12-69 months), 67 patients (69.1%) experienced recurrence and 41 patients (42.3%) were still alive. The median RFS and OS periods after LR were 29 and 45 months, respectively. The 1-, 3-, and 5-year RFS and OS rates were 88.7%, 41.2%, and 21.7% and 99.0%, 68.3%, and 25.6%, respectively. MK (P<0.001), PVT (P<0.001), and ADC (P=0.033) were identified as independent predictor factors for RFS. A nomogram including the MK value for RFS showed the best performance, and the C-index was 0.895. Conclusion: The MK value obtained from DKI is a potential predictive factor for recurrence and poor survival, which could provide valuable information for guiding the efficacy of LR in patients with large HCC.

Alterations of the gut microbiota in patients with immunoglobulin light chain amyloidosis.

Background: Emerging evidence revealed that gut microbial dysbiosis is implicated in the development of plasma cell dyscrasias and amyloid deposition diseases, but no data are available on the relationship between gut microbiota and immunoglobulin light chain (AL) amyloidosis. Methods: To characterize the gut microbiota in patients with AL amyloidosis, we collected fecal samples from patients with AL amyloidosis (n=27) and age-, gender-, and BMI-matched healthy controls (n=27), and conducted 16S rRNA MiSeq sequencing and amplicon sequence variants (ASV)-based analysis. Results: There were significant differences in gut microbial communities between the two groups. At the phylum level, the abundance of Actinobacteriota and Verrucomicrobiota was significantly higher, while Bacteroidota reduced remarkably in patients with AL amyloidosis. At the genus level, 17 genera, including Bifidobacterium, Akkermansia, and Streptococcus were enriched, while only 4 genera including Faecalibacterium, Tyzzerella, Pseudomonas, and Anaerostignum decreased evidently in patients with AL amyloidosis. Notably, 5 optimal ASV-based microbial markers were identified as the diagnostic model of AL amyloidosis and the AUC value of the train set and the test set was 0.8549 (95% CI 0.7310-0.9789) and 0.8025 (95% CI 0.5771-1), respectively. With a median follow-up of 19.0 months, further subgroup analysis also demonstrated some key gut microbial markers were related to disease severity, treatment response, and even prognosis of patients with AL amyloidosis. Conclusions: For the first time, we demonstrated the alterations of gut microbiota in AL amyloidosis and successfully established and validated the microbial-based diagnostic model, which boosted more studies about microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis in the future.

Liver resection, radiofrequency ablation, and radiofrequency ablation combined with transcatheter arterial chemoembolization for very-early- and early-stage hepatocellular carcinoma: A systematic review and Bayesian network meta-analysis for comparison of efficacy.

Objective: To compare the efficacy of liver resection (LR), radiofrequency ablation (RFA), and radiofrequency ablation combined with transcatheter arterial chemoembolization (RFA+TACE) in the treatment of very-early- and early-stage hepatocellular carcinoma (HCC). Methods: We systemically searched the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) and observational analyses with propensity score-matched cohort analyses (PSMs) comparing any two of the three treatments were included in this study. The primary result was overall survival (OS) and the secondary result was recurrence-free survival (RFS), which were analyzed by calculating the hazard ratio (HR) and 95% confidence intervals (CI). Results: A total of 25 studies (4249 patients), including 10 RCTs and 15 PSM observational studies, met the inclusion criteria. Although there was no significant difference between LR and RFA in terms of one-year OS, though LR showed superior performance for three- and five-year OS (at three years, HR: 0.74, 95% CI: 0.56-0.96; at five years, HR: 0.73, 95% CI: 0.55-0.94). In addition, significantly higher rates of RFS at one-, three- and five-year follow-up were found for LR than for RFA alone (at one year, HR: 0.68, 95% CI: 0.51-0.92; at three years, HR: 0.67, 95% CI: 0.55-0.81; at five years, HR: 0.61, 95% CI: 0.48-0.78). The combination of RFA+TACE was superior to RFA alone based on one-year RFS (HR: 0.57, 95% CI: 0.34-0.96), while there were no significant differences in OS at one, three, and five years, and in RFS at three and five years. Conclusions: For very-early- and early-stage HCC, this systematic review and network meta-analysis showed that the efficacy of LR is superior to that of RFA alone, regardless of whether the evaluation is based on either OS or RFS. The advantages of RFA+TACE compared to RFA alone are limited, and further studies are needed to determine whether combination therapy is necessary, i.e., results in significantly improved outcomes. Systematic Review Registration: The study was registered with http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022299269.

High-cutoff hemodialysis in multiple myeloma patients with acute kidney injury.

Multiple myeloma (MM), an incurable hematological malignancy with clonal proliferation of plasma cells, is mainly characterized by excessive production of monoclonal immunoglobulins and free light chains (FLCs). Kidney injury is one of the main clinical manifestations and is also a significant predictor of the prognosis of symptomatic MM patients, especially those who require dialysis-supported treatment. Overproduction of FLCs is the trigger for kidney injury, as they can induce the transcription of inflammatory and profibrotic cytokines in the proximal tubule and bind to Tamm-Horsfall protein in the distal tubules to form casts that obstruct the tubules, leading to kidney injury and even renal fibrosis. In addition to traditional antimyeloma treatment, high-cutoff hemodialysis (HCO-HD), which can effectively remove FLCs in vitro, has attracted much attention in recent years. Due to its greater membrane pore size, it has significant advantages in removing larger molecules and can be applied in rhabdomyolysis, sepsis, and even myeloma cast nephropathy. However, mounting questions have recently been raised regarding whether HCO-HD can truly provide clinical benefits in MM patients with acute kidney injury (AKI). Therefore, in this study, we discussed the pathological causes of AKI secondary to MM and summarized the current situation of HCO-HD in MM patients compared with other available extracorporeal techniques. In addition, pivotal clinical trials that reflect the ability of the clearance of FLCs and the side effects of HCO-HD are highlighted, and the relevant protocol of HCO-HD is also provided to assist clinicians in decision-making.

Specific alterations of gut microbiota in patients with membranous nephropathy: A systematic review and meta-analysis.

Background: The pathogenesis of idiopathic membranous nephropathy (IMN) has not yet been thoroughly clarified, and gut dysbiosis may be a contributor to IMN. However, the characterization of gut microbiota in patients with IMN remains uncertain. Methods: Cochrane Library, PubMed, China National Knowledge Internet, Web of Science, and Embase were used to search for studies through 18 May 2022. A meta-analysis based on the standardized mean difference (SMD) with 95% confidence interval (CI) was conducted on the alpha diversity index. The between-group comparison of the relative abundance of gut microbiota taxa and the beta diversity were extracted and qualitatively analyzed. Results: Five studies were included involving 290 patients with IMN, 100 healthy controls (HCs), and 129 patients with diabetic kidney disease (DKD). The quantitative combination of alpha diversity indices indicated that although bacterial richness was impaired [ACE, SMD = 0.12, (-0.28, 0.52), p = 0.55, I 2 = 0%; Chao1, SMD = -0.34, (-0.62, -0.06), p < 0.05, I 2 = 36%], overall diversity was preserved [Shannon, SMD = -0.16, (-0.64, 0.31), p = 0.50, I 2 = 53%; Simpson, SMD = 0.27, (-0.08, 0.61), p = 0.13, I 2 = 0%]. The beta diversity was significantly varied compared to HCs or DKD patients. Compared to HCs, the abundance of Proteobacteria increased, while that of Firmicutes decreased at the phylum level. Furthermore, the abundance of Lachnospira were depleted, while those of Streptococcus were enriched at the genus level. Proteobacteria and Streptococcus were also increased compared to DKD patients. Conclusions: The expansion of Proteobacteria and depletion of Lachnospira may be critical features of the altered gut microbiota in patients with IMN. This condition may play an important role in the pathogenesis of IMN and could provide bacterial targets for diagnosis and therapy.