Performance of a novel up-flow electrocatalytic hydrolysis acidification reactor (UEHAR) coupled with anoxic/oxic system for treating coking wastewater.

In this study, the performance of a novel up-flow electrocatalytic hydrolytic acidification reactor (UEHAR) and anoxic/oxic (ANO2/O2) combined system (S2) was compared with that of a traditional anaerobic/anoxic/oxic (ANA/ANO1/O1) system (S1) for treating coking wastewater at different hydraulic retention time (HRT). The effluent non-compliance rates of chemical oxygen demand (COD) of S2 were 45 %, 35 %, 25 % and 55 % lower than S1 with HRT of 94, 76, 65 and 54 h. The removal efficiency of benzene, toluene, ethylbenzene and xylene (BTEX) in S2 was 10.6 ± 2.4 % higher than that in S1. The effluent concentration of volatile phenolic compounds (VPs) in S2 was lower than 0.3 mg/L. The dehydrogenase activity (DHA) and adenosine triphosphate (ATP) of O2 were enhanced by 67.2 ± 26.3 % and 40.6 ± 14.2 % compared with O1, respectively. Moreover, COD was used to reflect the mineralization index of organic matter, and the positive correlation between COD removal rate and microbial activity, VPs, and BTEX was determined. These results indicated that S2 had extraordinary microbial activity, stable pollutant removal ability, and transcendental effluent compliance rate.

A deep learning-based method for the prediction of temporal lobe injury in patients with nasopharyngeal carcinoma.

PURPOSE: To establish a deep learning-based model to predict radiotherapy-induced temporal lobe injury (TLI). MATERIALS AND METHODS: Spatial features of dose distribution within the temporal lobe were extracted using both the three-dimensional convolution (C3D) network and the dosiomics method. The Minimal Redundancy-Maximal-Relevance (mRMR) method was employed to rank the extracted features and select the most relevant ones. Four machine learning (ML) classifiers, including logistic regression (LR), k-nearest neighbors (kNN), support vector machines (SVM) and random forest (RF), were used to establish prediction models. Nested sampling and hyperparameter tuning methods were applied to train and validate the prediction models. For comparison, a prediction model base on the conventional D0.5cc of the temporal lobe obtained from dose volume (DV) histogram was established. The area under the receiver operating characteristic (ROC) curve (AUC) was utilized to compare the predictive performance of the different models. RESULTS: A total of 127 nasopharyngeal carcinoma (NPC) patients were included in the study. In the model based on C3D deep learning features, the highest AUC value of 0.843 was achieved with 5 features. For the dosiomics features model, the highest AUC value of 0.715 was attained with 1 feature. Both of these models demonstrated superior performance compared to the prediction model based on DV parameters, which yielded an AUC of 0.695. CONCLUSION: The prediction model utilizing C3D deep learning features outperformed models based on dosiomics features or traditional parameters in predicting the onset of TLI. This approach holds promise for predicting radiation-induced toxicities and guide individualized radiotherapy.

Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions.

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. METHODS: Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. RESULTS: PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -ß1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1ß and tumour necrosis factor α (TNF-α) were significantly lower. CONCLUSIONS: We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer.

BACKGROUND Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer, accounting for 12-18% of all breast cancer cases. It exhibits high heterogeneity and aggressiveness, resulting in a poorer prognosis with a high risk of early recurrence and metastasis. Due to the lack of expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), as well as insensitivity to endocrine therapy, determining a standard treatment for TNBC is challenging. The identification of potential prognostic biomarkers is crucial for developing personalized treatment strategies for patients. MATERIAL AND METHODS Our study investigated the potential value of HSP90a in TNBC prognosis. A retrospective analysis was conducted on 127 TNBC patients and 127 Healthy controls from March 1, 2019 to July 31, 2022. Venous blood was collected and tested for HSP90alpha, CEA, CA199, and CA125, and we recorded the clinical characteristics of the patients, including age, BMI, alcohol consumption status, surgical history, CEA level, CA199 level, CA125 level, HSP90alpha level, tumor size, distant metastases, lymph node metastasis, and TNM stage. Univariate and multivariate methods were used to screen independent risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS HSP90alpha is not only upregulated in TNBC but is also highly correlated with lymph node metastasis and TNM stage. The results of multivariate analysis showed that distant metastasis, TNM stage and HSP90a level were independent factors associated with PFS. BMI, tumor size, TNM stage, surgical history, and HSP90a level were independent factors influencing OS. CONCLUSIONS Our research findings demonstrate a significant association between high HSP90alpha expression and adverse clinical features, suggesting a poorer prognosis for TNBC patients.

Intratumor tertiary lymphatic structure evaluation predicts the prognosis and immunotherapy response of patients with colorectal cancer.

Background: Immune checkpoint therapy, involving the programmed cell death 1 (PD-1) monoclonal antibody, has revolutionized the treatment of cancer. Tertiary lymphatic structure (TLS) serves as an immune indicator to predict the efficacy of PD-1 antibody therapy. However, there is no clear result whether the distribution, quantity, and maturity of TLS can be effective indicators for predicting the clinical efficacy of anti-PD1 immunotherapy in patients with colorectal cancer (CRC). Methods: Fifty-seven patients who underwent surgical resection and thirty-nine patients who received anti-PD-1 immunotherapy were enrolled in this retrospective study. Immunohistochemical staining and multiple fluorescence immunohistochemistry were used to evaluate the mismatch repair (MMR) subtypes and TLS distribution, quantity, and maturity, respectively. Results: A comprehensive patient score system was built based on TLS quantity and maturity. We found that the proportion of patients with score >1 was much higher in the deficient mismatch repair(dMMR) group than in the proficient mismatch repair(pMMR) group, and this difference was mainly due to intratumoral TLS. Patient score, based on the TLS evaluation of whole tumor, peritumor, or intratumor, was used to evaluate the efficacy of anti-PD1 immunotherapy. Based only on the intratumor TLS evaluation, the proportion of patients with a score >1 was higher in the response (PR + CR) group than in the non-response (PD) group. Multivariate analysis revealed that patient scores were positively correlated with the clinical efficacy of immunotherapy. Further analysis of immune-related progression-free survival was performed in patients with CRC who received anti-PD-1 immunotherapy. Patients with score >1 based on the intratumor TLS evaluation had significantly better survival. Conclusions: These results suggest that the patient score based on intratumor TLS evaluation may be a good immune predictive indicator for PD-1 antibody therapy in patients with CRC.

Spermidine attenuates monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting purine metabolism and polyamine synthesis-associated vascular remodeling.

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

BACKGROUND: It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. METHODS AND RESULTS: In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. CONCLUSIONS: Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

The individualized delineation of clinical target volume for primary nasopharyngeal carcinoma based on invasion risk of substructures: A prospective, real-world study with a large population.

BACKGROUND AND PURPOSE: The delineation of clinical target volume (CTV) for primary nasopharyngeal carcinoma (NPC) is currently controversial and the international guideline still recommend a uniform border for CTV regardless of the tumor extent. We conducted this prospective, real-world study to evaluate the clinical outcomes of our individualized CTV delineation method based on distance plus substructures. MATERIALS AND METHODS: We preliminarily investigated the local extension patterns of NPC on 354 newly diagnosed patients and defined the structures surrounding the nasopharynx as Level-1 to Level-4 substructures stratified by the risk of invasion. We then enrolled patients with newly diagnosed NPC without distant metastasis to investigate our individualized CTV delineation protocol. All patients received intensity modulated radiotherapy. CTV1 and CTV2 were prescribed doses of 60 Gy and 54 Gy in 30 âˆ¼ 33 fractions. The primary endpoint was local recurrence-free survival (LRFS); secondary endpoints included regional control and survival, estimated using the Kaplan-Meier method. The local failure patterns were also analyzed. RESULTS: From January 2008 to December 2012 and from January 2013 to September 2019, 356 and 648 patients were enrolled, named as training set and validation set, respectively. With a median follow-up of 104.6 (interquartile, 73.1-126.9) and 51.4 (39.5-78.5) months, 31 (8.7 %) and 38 (5.9 %) patients in training and validation sets experienced local recurrence, and the 5-year LRFS was 93.0 % and 93.2 %, respectively; 63 (17.7 %) and 39 (6 %) patients died in training and validation sets, and the 5-year overall survival (OS) was 88.5 % and 93.4 %, respectively. For the whole study cohort (N = 1004) with a median follow-up of 66.6 (41.5-98.0) months, the 5-year LRFS and OS was 93.2 % and 91.5 %. The grade 3 late toxicities included xerostomia, subcutaneous fibrosis, hearing impairment, trismus, visuality impairment and skin atrophy, with a total incidence of 1.5 %. Sixty-seven of 69 (97.1 %) local recurrence was in high-dose area. CONCLUSION: Our individualized CTV delineation method can achieve favorable local tumor control and long-term survival outcomes with acceptable late toxicities.

Hydroxy-Safflower Yellow A Mitigates Vascular Remodeling in Rat Pulmonary Arterial Hypertension.

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.

Transcriptome-wide quantitative profiling of PUS7-dependent pseudouridylation by nanopore direct long read RNA sequencing.

Pseudouridylation is a prevalent post-transcriptional RNA modification that impacts many aspects of RNA biology and function. The conversion of uridine to pseudouridine (Ψ) is catalyzed by the family of pseudouridine synthases (PUSs). Development of robust methods to determine PUS-dependent regulation of Ψ location and stoichiometry in low abundant mRNA is essential for biological and functional understanding of pseudouridylation. Here, we present a framework, NanoPsiPy, for identifying Ψ sites and quantify their levels in poly-A RNA at single-nucleotide resolution using direct RNA long-read Nanopore sequencing, based on the observation that Ψ can cause characteristic U-to-C basecalling errors in Nanopore direct RNA sequencing data. Our method was able to detect low and high stoichiometric Ψ sites in human mRNA. We validated our method by transcriptome-wide quantitative profiling of PUS7-dependent Ψ sites in poly-A RNA from a MYCN -amplified neuroblastoma cell line. We identified 8,625 PUS7-dependent Ψ sites in 1,246 mRNAs that encode proteins involved primarily in ribosome biogenesis, translation, and mitochondrial energy metabolism. Our work provides the first example of using direct RNA long-read Nanopore sequencing for transcriptome-wide quantitative profiling of mRNA pseudouridylation regulated by a PUS. We envision that our method will facilitate functional interrogation of PUSs in biological and pathological processes.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Alterations of B-Cell subsets in Peripheral Blood from Adult Patients with Idiopathic Membranous Nephropathy.

OBJECTIVES: Idiopathic membranous nephropathy (MN) is an autoimmune disease characterized by specific antibodies. However, the underlying mechanisms by which lymphocytes promote the development of MN remain poorly understood. This study aims to determine the changes of B-cell subsets and their clinical significance in MN patients. METHODS: We included a cohort of 21 idiopathic MN patients with new onset or a relapse, 19 healthy controls (HCs) and 10 patients with minimal change disease (MCD). Immunohistochemistry and flow cytometry were performed to assess the B-cell infiltration in renal biopsy tissues and peripheral blood, respectively. RESULTS: Idiopathic MN patients (including new-onset and relapse groups) had lower percentages of marginal-zone B (MZB) and non-switched memory B cells, and higher percentages of plasmablasts than HCs (P < 0.01). Particularly, the new-onset group had lower percentages of switched memory B cells and MZB cells, and higher percentages of Naïve B cells than HCs (P<0.05). Interestingly, the percentage of plasmablasts was significantly correlated with urine protein to creatinine ratio, serum albumin, IgG, anti-M-type phospholipase A2 receptor antibody level and age in MN patients (P < 0.05). MN with Ehrenreich-Churg stage Ⅱ-Ⅳ had a lower median percentage of MZB and non-switched memory B cells, while a higher median percentage of plasmablasts than those in MN patients with stage Ehrenreich-Churg I (P < 0.05). CONCLUSION: Idiopathic MN patients had specific changes in B-cell subsets proportions in peripheral blood. Further studies are needed to precisely determine the roles of B-cell subsets in MN.

Clinical characteristics and prognostic factors in nasopharyngeal carcinoma with brain metastasis: A retrospective, single-center study.

BACKGROUND: Brain metastasis is rare in nasopharyngeal carcinoma (NPC), with only anecdotal cases reported. Conducting a systematic study is crucial for improving the management of these patients. MATERIALS AND METHODS: Forty-one patients with brain metastasis were retrospectively included between February 2000 and February 2023. The clinical characteristics and treatment information of patients were analyzed. Overall survival (OS) was estimated by Kaplan-Meier survival analysis, and Cox proportional hazard regression analysis was performed to explore prognostic factors. RESULTS: The median OS for patients was 11.2 months, with a 3-year OS rate of 16.3%. The number of extracranial metastatic organs (HR = 5.533, P = 0.041) and the response of extracranial tumors to treatment (HR = 0.079, P = 0.003) were independent prognostic factors in the cohort. CONCLUSIONS: Brain metastasis in NPC is a devastating condition that commonly occurs through hematogenous dissemination. Systemic therapy remains fundamental treatment, while local therapy for brain metastases may further improve survival in selected patients.

Blockade of BLyS inhibits B-cell responses and antibody production for the prevention of chronic transplant rejection.

BACKGROUND: Chronic rejection, closely related to the activation of B cells and donor-specific antibody (DSA) production, has unsatisfactory therapeutic outcomes. B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the activation and differentiation of B cells. However, it remains unclear whether BLyS blockade can regulate B and plasma cells in the transplantation setting and affect chronic rejection. Here, we investigated the efficacy of the BLyS inhibitors belimumab and telitacicept in controlling B-cell response and preventing chronic rejection. METHODS: The effects of belimumab and telitacicept on B-cell activation, differentiation, and antibody production in vitro were determined. A chronic rejection model in mouse was established by allogeneic cardiac transplantation with CTLA4-Ig treatment. Allograft survival, histology, DSA levels, and B-cell responses were analyzed to evaluate the chronic rejection-preventive effects of belimumab and telitacicept. RESULTS: In vitro experiments confirmed that belimumab and telitacicept inhibited B-cell activation and differentiation and reduced antibody production. In vivo experiments indicated that they significantly prolonged allograft survival, attenuated chronic rejection through significant suppression of myocardial ischemic necrosis and interstitial fibrosis, and reduced DSA-IgG levels, C4d deposition, and inflammatory cell infiltration. Furthermore, the frequencies of B cells, plasma cells, and IgG-producing cells in the recipients' spleen, lymph nodes, bone marrow, and blood were decreased after BLyS inhibitors treatment. CONCLUSIONS: This study demonstrated that belimumab and telitacicept inhibit B-cell responses and antibody production and alleviate chronic transplant rejection. Therefore, BLyS inhibitors are expected to be used for the prevention of chronic rejection in clinical practice.

Efficacy of Rituximab for Minimal Change Disease and Focal Segmental Glomerulosclerosis with Frequently Relapsing or Steroid-Dependent Nephrotic Syndrome in Adults: A Chinese Multicenter Retrospective Study.

INTRODUCTION: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). METHODS: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse. RESULTS: Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment. CONCLUSION: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

A nomogram predicting the histologic activity of lupus nephritis from clinical parameters.

BACKGROUND: The 2021 clinical guidelines of the Kidney Disease: Improving Global Outcomes emphasize the importance of the histological activity index (AI) in the management of lupus nephritis (LN). Patients with LN and a high AI have poor renal outcomes and high rates of nephritic relapse. In this study we constructed prediction models for the AI in LN. METHODS: The study population comprised 337 patients diagnosed with LN using kidney biopsy. The participants were randomly divided into training and testing cohorts. They were further divided into high-activity (AI >2) and low-activity (AI ≤2) groups. This study developed two clinical prediction models using logistic regression and least absolute shrinkage and selection operator (LASSO) analyses with laboratory test results collected at the time of kidney biopsy. The performance of models was assessed using 5-fold cross-validation and validated in the testing cohort. A nomogram for individual assessment was constructed based on the preferable model. RESULTS: Multivariate analysis showed that higher mean arterial pressure, lower estimated glomerular filtration rate, lower complement 3 level, higher urinary erythrocytes count and anti-double-stranded DNA seropositivity were independent risk factors for high histologic activity in LN. Both models performed well in the testing cohort regarding the discriminatory ability to identify patients with an AI >2. The average area under the curve of 5-fold cross-validation was 0.855 in the logistic model and 0.896 in the LASSO model. A webtool based on the LASSO model was created for clinicians to enter baseline clinical parameters to produce a probability score of an AI >2. CONCLUSIONS: The established nomogram provides a quantitative auxiliary tool for distinguishing LN patients with a high AI and helps physicians make clinical decisions in their comprehensive assessment.

Limonoids from the Branches and Leaves of Aglaia lawii and Their Cytotoxic Activities.

Three undescribed limonoids (1-3), named aglaians G-I, and one new natural product azedaralide (4), together with nine known analogues (5-13) were isolated from the branches and leaves of Aglaia lawii by RP C18 column, silica gel column, Sephadex LH-20 column chromatography and preparative HPLC. The structures of the new compounds were elucidated by IR, HRESIMS, 1D, 2D NMR, electronic circular dichroism (ECD) calculations and X-ray crystallography diffraction analysis. The results of bioassay showed that the compound 12 exhibited potential inhibitory activity against six human tumor cell lines (MDA-MB-231, MCF-7, Ln-cap, A549, HeLa and HepG-2) with IC50 values as 8.0-18.6 µM.

Renal macrophages monitor and remove particles from urine to prevent tubule obstruction.

When the filtrate of the glomerulus flows through the renal tubular system, various microscopic sediment particles, including mineral crystals, are generated. Dislodging these particles is critical to ensuring the free flow of filtrate, whereas failure to remove them will result in kidney stone formation and obstruction. However, the underlying mechanism for the clearance is unclear. Here, using high-resolution microscopy, we found that the juxtatubular macrophages in the renal medulla constitutively formed transepithelial protrusions and "sampled" urine contents. They efficiently sequestered and phagocytosed intraluminal sediment particles and occasionally transmigrated to the tubule lumen to escort the excretion of urine particles. Mice with decreased renal macrophage numbers were prone to developing various intratubular sediments, including kidney stones. Mechanistically, the transepithelial behaviors of medulla macrophages required integrin ß1-mediated ligation to the tubular epithelium. These findings indicate that medulla macrophages sample urine content and remove intratubular particles to keep the tubular system unobstructed.