Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability.

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient's kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

Genome-wide characterization and expression analysis of α-amylase and ß-amylase genes underlying drought tolerance in cassava.

BACKGROUND: Starch hydrolysates are energy sources for plant growth and development, regulate osmotic pressure and transmit signals in response to both biological and abiotic stresses. The α-amylase (AMY) and the ß-amylase (BAM) are important enzymes that catalyze the hydrolysis of plant starch. Cassava (Manihot esculenta Crantz) is treated as one of the most drought-tolerant crops. However, the mechanisms of how AMY and BAM respond to drought in cassava are still unknown. RESULTS: Six MeAMY genes and ten MeBAM genes were identified and characterized in the cassava genome. Both MeAMY and MeBAM gene families contain four genes with alternative splicing. Tandem and fragment replications play important roles in the amplification of MeAMY and MeBAM genes. Both MeBAM5 and MeBAM10 have a BZR1/BES1 domain at the N-terminus, which may have transcription factor functions. The promoter regions of MeAMY and MeBAM genes contain a large number of cis-acting elements related to abiotic stress. MeAMY1, MeAMY2, MeAMY5, and MeBAM3 are proven as critical genes in response to drought stress according to their expression patterns under drought. The starch content, soluble sugar content, and amylase activity were significantly altered in cassava under different levels of drought stress. CONCLUSIONS: These results provide fundamental knowledge for not only further exploring the starch metabolism functions of cassava under drought stress but also offering new perspectives for understanding the mechanism of how cassava survives and develops under drought.

Effectiveness of Chinese herbal medicine combined with Western medicine on deferring dialysis initiation for nondialysis chronic kidney disease stage 5 patients: a multicenter prospective nonrandomized controlled study.

BACKGROUND: In clinical practice, Chinese herbal medicine (CHM) purportedly has beneficial therapeutic effects for chronic kidney disease (CKD), which include delaying disease progression and dialysis initiation. However, there is a lack of high-quality evidence-based results to support this. Therefore, this study aimed to evaluate the efficacy of CHM combined with Western medicine in the treatment of stage 5 CKD. METHODS: This was a prospective nonrandomized controlled study. Stage 5 CKD (nondialysis) patients were recruited form 29 AAA class hospitals across China from July 2014 to April 2019. According to doctors' advice and the patients' wishes, patients were assigned to the CHM group (Western medicine + CHM) and the non-CHM group (Western medicine). Patient demographic data, primary disease, blood pressure, Chinese and Western medical drugs, clinical test results, and time of dialysis initiation were collected during follow-up. RESULTS: A total of 908 patients were recruited in this study, and 814 patients were finally included for further analysis, including 747 patients in the CHM group and 67 patients in the non-CHM group. 482 patients in the CHM group and 52 patients in the non-CHM group initiated dialysis. The median time of initiating dialysis was 9 (7.90, 10.10) and 3 (0.98,5.02) months in the CHM group and non-CHM group, respectively. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis [adjusted hazard ratio (aHR): 0.38; 95% confidence interval (CI): 0.28, 0.53] compared to those in the non-CHM group. After 1:2 matching, the outcomes of 160 patients were analyzed. The multivariate Cox regression analysis showed that patients in the CHM group had a significantly lower risk of dialysis (aHR: 0.32; 95% CI: 0.21, 0.48) compared to patients in the non-CHM group. Also, the Kaplan-Meier analysis demonstrated that the cumulative incidence of dialysis in the CHM group was significantly lower than that in the non-CHM group (log-rank test, P<0.001) before and after matching. CONCLUSIONS: This study suggest that the combination of CHM and Western medicine could effectively reduce the incidence of dialysis and delay the time of dialysis initiation in stage 5 CKD patients.

Family history information extraction via deep joint learning.

BACKGROUND: Family history (FH) information, including family members, side of family of family members (i.e., maternal or paternal), living status of family members, observations (diseases) of family members, etc., is very important in the decision-making process of disorder diagnosis and treatment. However FH information cannot be used directly by computers as it is always embedded in unstructured text in electronic health records (EHRs). In order to extract FH information form clinical text, there is a need of natural language processing (NLP). In the BioCreative/OHNLP2018 challenge, there is a task regarding FH extraction (i.e., task1), including two subtasks: (1) entity identification, identifying family members and their observations (diseases) mentioned in clinical text; (2) family history extraction, extracting side of family of family members, living status of family members, and observations of family members. For this task, we propose a system based on deep joint learning methods to extract FH information. Our system achieves the highest F1- scores of 0.8901 on subtask1 and 0.6359 on subtask2, respectively.

Benchmark Calculations of Three-Body Intermolecular Interactions and the Performance of Low-Cost Electronic Structure Methods.

Many-body noncovalent interactions are increasingly important in large and/or condensed-phase systems, but the current understanding of how well various models predict these interactions is limited. Here, benchmark complete-basis set coupled cluster singles, doubles, and perturbative triples (CCSD(T)) calculations have been performed to generate a new test set for three-body intermolecular interactions. This "3B-69" benchmark set includes three-body interaction energies for 69 total trimer structures, consisting of three structures from each of 23 different molecular crystals. By including structures that exhibit a variety of intermolecular interactions and packing arrangements, this set provides a stringent test for the ability of electronic structure methods to describe the correct physics involved in the interactions. Both MP2.5 (the average of second- and third-order Møller-Plesset perturbation theory) and spin-component-scaled CCSD for noncovalent interactions (SCS-MI-CCSD) perform well. MP2 handles the polarization aspects reasonably well, but it omits three-body dispersion. In contrast, many widely used density functionals corrected with three-body D3 dispersion correction perform comparatively poorly. The primary difficulty stems from the treatment of exchange and polarization in the functionals rather than from the dispersion correction, though the three-body dispersion may also be moderately underestimated by the D3 correction.

Prevalence and Impact on Stroke in Patients Receiving Maintenance Hemodialysis versus Peritoneal Dialysis: A Prospective Observational Study.

BACKGROUND: Patients undergoing maintenance dialysis are at increased risk of stroke, however, less is known about the prevalence and impact on stroke in the patients. METHODS: In this prospective cohort study, 590 patients undergoing hemodialysis (HD; n = 285) or peritoneal dialysis (PD; n = 305) from January 1, 2008 to December 31, 2012 were recruited. Baseline demographic, clinical, and laboratory data were collected. Timeline incidence data were analyzed using a Poisson model. The Cox proportional hazards regression assessed adjusted differences in stroke risk, a multivariate analysis was also performed. RESULTS: 62 strokes occurred during 1258 total patient-years of follow-up. Stroke occurred at a rate of 49.2/1,000 patient-years with a predominance in HD patients compared with PD patients (74.0 vs. 31.8/1,000 patient-years). The cumulative hazard of developing stroke was significantly higher in HD patients (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.15-3.62; p = 0.046) after adjusting for potential confounders. HD patients had an increased risk of ischemic stroke (HR, 2.62; 95% CI, 1.56-4.58; p = 0.002). The risk of hemorrhagic stroke was not significantly different between PD and HD patients. On multivariate Cox analysis, risk factors of stroke in both HD and PD patients were older age, diabetes, and cardiovascular disease. Other independent risk factors of stroke were lower albumin-corrected calcium in HD patients and higher triglycerides in PD patients. CONCLUSIONS: Patients undergoing PD were less likely to develop ischemic stroke than those undergoing HD. Comprehensive control of diabetes, cardiovascular disease, calcium-phosphorus metabolism, and triglyceride levels may be useful preventive strategies for stroke in dialysis patients.

Reliable prediction of three-body intermolecular interactions using dispersion-corrected second-order Møller-Plesset perturbation theory.

Three-body and higher intermolecular interactions can play an important role in molecular condensed phases. Recent benchmark calculations found problematic behavior for many widely used density functional approximations in treating 3-body intermolecular interactions. Here, we demonstrate that the combination of second-order Møller-Plesset (MP2) perturbation theory plus short-range damped Axilrod-Teller-Muto (ATM) dispersion accurately describes 3-body interactions with reasonable computational cost. The empirical damping function used in the ATM dispersion term compensates both for the absence of higher-order dispersion contributions beyond the triple-dipole ATM term and non-additive short-range exchange terms which arise in third-order perturbation theory and beyond. Empirical damping enables this simple model to out-perform a non-expanded coupled Kohn-Sham dispersion correction for 3-body intermolecular dispersion. The MP2 plus ATM dispersion model approaches the accuracy of O(N(6)) methods like MP2.5 or even spin-component-scaled coupled cluster models for 3-body intermolecular interactions with only O(N(5)) computational cost.

Neutrophil Gelatinase-associated Lipocalin in the Prediction of Contrast-induced Nephropathy: A Systemic Review and Meta-analysis.

OBJECTIVE: The aim of this study was to investigate the predictive value of neutrophil gelatinase-associated lipocalin (NGAL) in the early diagnosis of contrast-induced nephropathy (CIN). METHODS: We searched MEDLINE and Embase until December 2014 for articles evaluating the diagnostic accuracy of plasma/serum and urinary NGAL levels to predict CIN. The primary analysis was based on a hierarchical, bivariate, generalized, linear, mixed model. Diagnostic odds ratio (DOR) and sample size-weighted area under the curve for the receiver operating characteristic (AUROC) were calculated. RESULTS: Ten studies involving 1310 patients were analyzed. Overall, the DOR/AUROC for NGAL level to predict CIN was 20.56 [95% confidence interval (CI), 9.67-43.74]/0.87 (95% CI, 0.84-0.90), with sensitivity and specificity of 0.80 (95% CI, 0.74-0.85) and 0.83 (95% CI, 0.73-0.90), respectively. Subgroup analysis showed that the diagnostic performance of the DOR/AUROC of urinary NGAL [29.48 (95% CI, 12.19-71.27)/0.87 (95% CI, 0.84-0.90)] was better than that of plasma/serum NGAL [14.63 (95% CI, 4.51-47.38)/0.85 (95% CI, 0.82-0.88)] (DOR, P = 0.005, and AUROC, P = 0.04, respectively). CONCLUSIONS: Plasma/serum and urinary NGAL levels seem to be useful biomarkers in the early prediction of CIN. Moreover, urinary NGAL levels perform better than plasma/serum NGAL.

Calcium acetate or calcium carbonate for hyperphosphatemia of hemodialysis patients: a meta-analysis.

BACKGROUND: High levels of serum phosphorus both at baseline and during follow-up are associated with increased mortality in dialysis patients, and administration of phosphate binders was independently associated with improved survival among hemodialysis population. Calcium-based phosphate binders are the most commonly used phosphate binders in developing countries for their relatively low costs. OBJECTIVES: To compare the efficacy and safety between calcium carbonate and calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. METHODS: PubMed, EMBASE, Cochrane Library, Google scholar and Chinese databases (Wanfang, Weipu, National Knowledge Infrastructure of China) were searched for relevant studies published before March 2014. Reference lists of nephrology textbooks and review articles were checked. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of calcium acetate and calcium carbonate in adult patients with MHD was performed using Review Manager 5.0. RESULTS: A total of ten studies (625 participants) were included in this meta-analysis. There was insufficient data in all-cause mortality and cardiovascular events for meta-analysis. Compared with calcium carbonate group, the serum phosphorus was significantly lower in calcium acetate group after4 weeks' administration (MD -0.15 mmol/L, 95% CI -0.28 to -0.01) and after 8 weeks' administration (MD -0.25 mmol/L, 95% CI -0.40 to -0.11). There was no difference in serum calcium levels or the incidence of hypercalcemia between two groups at 4 weeks and 8 weeks. No statistical difference was found in parathyroid hormone (PTH) levels or serum calcium by phosphorus (Ca x P) product. There was significantly higher risk of intolerance with calcium acetate treatment (RR 3.46, 95% CI 1.48 to 8.26). CONCLUSIONS: For hyperphosphatemia treatment, calcium acetate showed better efficacy and with a higher incidence of intolerance compared with calcium carbonate. There are insufficient data to establish the comparative superiority of the two calcium-based phosphate binders on all-cause mortality and cardiovascular end-points in hemodialysis patients.

miR-141 regulates TGF-ß1-induced epithelial-mesenchymal transition through repression of HIPK2 expression in renal tubular epithelial cells.

Epithelial-mesenchymal transition (EMT) plays a critical role in embryonic development, wound healing, tissue regeneration, cancer progression and organ fibrosis. The proximal tubular epithelial cells undergo EMT, resulting in matrix-producing fibroblasts and thereby contribute to the pathogenesis of renal fibrosis. The profibrotic cytokine, TGF­ß, is now recognized as the main pathogenic driver that has been shown to induce EMT in tubular epithelial cells. Increasing evidence indicate that HIPK2 dysfunction may play a role in fibroblasts behavior, and therefore, HIPK2 may be considered as a novel potential target for anti-fibrosis therapy. Recently, members of the miR-200 family (miR­200a, b and c and miR­141) have been shown to inhibit EMT. However, the steps of the multifactorial renal fibrosis progression that these miRNAs regulate, particularly miR­141, are unclear. To study the functional importance of miR­141 in EMT, a well­established in vitro EMT assay was used to demonstrate renal tubulointerstitial fibrosis; transforming growth factor­ß1­induced EMT in HK-2 cells. Overexpression of miR­141 in HK­2 cells, either with or without TGF­ß1 treatment, hindered EMT by enhancing E­cadherin and decreasing vimentin and fibroblast­specific protein 1 expression. miR­141 expression was repressed during EMT in a dose­ and time­dependent manner through upregulation of HIPK2 expression. Ectopic expression of HIPK2 promoted EMT by decreasing E-cadherin. Furthermore, co-transfection of miR­141 with the HIPK2 ORF clone partially inhibited EMT by restoring E­cadherin expression. miR­141 downregulated the expression of HIPK2 via direct interaction with the 3'-untranslated region of HIPK2. Taken together, these findings aid in the understanding of the role and mechanism of miR­141 in regulating renal fibrosis via the TGF­ß1/miR-141/HIPK2/EMT axis, and miR-141 may represent novel biomarkers and therapeutic targets in the treatment of renal fibrosis.

Achieving High-Accuracy Intermolecular Interactions by Combining Coulomb-Attenuated Second-Order Møller-Plesset Perturbation Theory with Coupled Kohn-Sham Dispersion.

The dispersion-corrected second-order Møller-Plesset perturbation theory (MP2C) approach accurately describes intermolecular interactions in many systems. MP2C, however, expends much computational effort to compute the long-range correlation with MP2, only to discard and replace those contributions with a simpler long-range dispersion correction based on intermolecular perturbation theory. Here, we demonstrate that one can avoid calculating the long-range MP2 correlation by attenuating the Coulomb operator, allowing the dispersion correction to handle the long-range interactions inexpensively. With relatively modest Coulomb attenuation, one obtains results that are very similar to those from conventional MP2C. With more aggressive attenuation, one can remove just enough short-range repulsive exchange-dispersion interactions to compensate for finite basis set errors. Doing so makes it possible to approach complete basis set limit quality results with only an aug-cc-pVTZ basis, resulting in substantial computational savings. Further computational savings could be achieved by reformulating the MP2C algorithm to exploit the increased sparsity of the two-electron integrals.

Accurate and robust molecular crystal modeling using fragment-based electronic structure methods.

Accurately modeling molecular crystal polymorphism requires careful treatment of diverse intra- and intermolecular interactions which can be difficult to achieve without the use of high-level ab initio electronic structure techniques. Fragment-based methods like the hybrid many-body interaction QM/MM technique enable the application of accurate electronic structure models to chemically interesting molecular crystals. The theoretical underpinnings of this approach and the practical requirements for the QM and MM contributions are discussed. Benchmark results and representative applications to aspirin and oxalyl dihydrazide crystals are presented.

Accelerating MP2C dispersion corrections for dimers and molecular crystals.

The MP2C dispersion correction of Pitonak and Hesselmann [J. Chem. Theory Comput. 6, 168 (2010)] substantially improves the performance of second-order Møller-Plesset perturbation theory for non-covalent interactions, albeit with non-trivial computational cost. Here, the MP2C correction is computed in a monomer-centered basis instead of a dimer-centered one. When applied to a single dimer MP2 calculation, this change accelerates the MP2C dispersion correction several-fold while introducing only trivial new errors. More significantly, in the context of fragment-based molecular crystal studies, combination of the new monomer basis algorithm and the periodic symmetry of the crystal reduces the cost of computing the dispersion correction by two orders of magnitude. This speed-up reduces the MP2C dispersion correction calculation from a significant computational expense to a negligible one in crystals like aspirin or oxalyl dihydrazide, without compromising accuracy.

Practical quantum mechanics-based fragment methods for predicting molecular crystal properties.

Significant advances in fragment-based electronic structure methods have created a real alternative to force-field and density functional techniques in condensed-phase problems such as molecular crystals. This perspective article highlights some of the important challenges in modeling molecular crystals and discusses techniques for addressing them. First, we survey recent developments in fragment-based methods for molecular crystals. Second, we use examples from our own recent research on a fragment-based QM/MM method, the hybrid many-body interaction (HMBI) model, to analyze the physical requirements for a practical and effective molecular crystal model chemistry. We demonstrate that it is possible to predict molecular crystal lattice energies to within a couple kJ mol(-1) and lattice parameters to within a few percent in small-molecule crystals. Fragment methods provide a systematically improvable approach to making predictions in the condensed phase, which is critical to making robust predictions regarding the subtle energy differences found in molecular crystals.

[Comparative study on sequential colon dialysis, hemodialysis and peritoneal dialysis in patients with hyperuricemia].

OBJECTIVE: To evaluate the effects of sequential colon dialysis (SCD), hemodialysis (HD) and peritoneal dialysis (PD) on the serum level of uric acid (UA) in patients with hyperuricemia. METHODS: A total of 293 patients with mild, moderate and severe degree of hyperuricemia were randomly assigned to three groups according to digital randomized method, and treated with SCD, HD and PD respectively. The serum level of UA was determined with unicase-peroxidase conjugate method, the blood levels of K+, Na+, Cl-, Ca2+ were determined by automatic biochemical analysor, and changes of body weight were measured before and after dialysis. RESULTS: In the 293 cases, the three modes of dialysis showed no difference in lowering uric acid in patients of mild degree (P > 0.05). But the HD did show a better efficacy than that of the other two in severe degree patients (P<0.01), while in patients of moderate degree, significant difference (P<0.01) showed between HD and SCD, PD and SCD, but not between HD and PD (P > 0.05). No obvious effect of the various modes of dialysis on the level of K+, Na+, Cl-, Ca2+, body weight. CONCLUSION: SCD can decrease the serum level of UA effectively and reduce the incidence of complication of hyperuricemia to some extent, as hemodialysis and peritoneal dialysis can.

[Combination therapy with losartan and fosinopril for early diabetic nephropathy].

OBJECTIVE: To observe the effects of combined use of losartan and fosinopril in the treatment of early diabetic nephropathy. METHODS: Fifty-seven patients with diabetic nephropathy were divided equally into group A with treatment with losartan (50 mg) and fosinopril (10 mg) daily, group B with daily losartan treatment (50-100 mg), and group C with fosinopril treatment at the daily dose of 10-20 mg. After the 6-month medication, the patients underwent examinations for changes in the mean arterial blood pressure (MABP), serum creatinine (SCr), blood urea nitrogen (BUN) and 24-h urine protein excretion. RESULTS: Losartan or fosinopril used alone or in combination significantly lowered MABP, 24-h urine protein excretion, SCr and BUN in the patients ( P < 0.05 or P < 0.01). In spite of the absence of significant differences between the patient groups, combination use of the two drugs produced the most obvious reduction of the parameters measured. CONCLUSION: Combined use of losartan and fosinopril may decrease MABP, 24-h urine protein excretion, SCr and BUN to a greater extent than the use of losartan or fosinopril alone.

[Effect of angiotensin-converting enzyme inhibitors on serum levels of erythropoietin in patients on peritoneal dialysis].

OBJECTIVE: To assess the effect of angiotensin-converting enzyme inhibitors (ACEI) on the serum level of erythropoietin (EPO) in patients receiving peritoneal dialysis and explore the possible mechanism. METHODS: Thirty-six patients receiving peritoneal dialysis were enrolled in this study, among whom 26 received EPO treatment and the other 10 did not. The 2 groups were randomly subdivided into experimental group and control group with equal cases in each, the former with ACEI prescription to control blood pressure while the latter with calcium channel blocker or alpha-receptor blocker. Serum levels of EPO and hemoglobin (Hb) in all the patients were determined before and 6 months after their respective therapies. RESULTS: The serum levels of EPO and Hb decreased significantly after therapy in the experimental group (P<0.05), obviously lower than those in the control group (P<0.05). CONCLUSION: ACEI may decrease the serum EPO and Hb levels in patients receiving peritoneal dialysis.