A nomogram based on peripheral lymphocyte for predicting 8-year survival in patients with prostate cancer: a single-center study using LASSO-cox regression.

PURPOSE: The purpose of this study was to develop a functional clinical nomogram for predicting 8-year overall survival (OS) of patients with prostate cancer (PCa) primary based on peripheral lymphocyte. PATIENTS AND METHODS: Using data from a single-institutional registry of 94 patients with PCa in China, this study identified and integrated significant prognostic factors for survival to build a nomogram. The discriminative ability was measured by concordance index (C-index) and ROC curves (Receiver Operating Characteristic Curves). And the predictive accuracy was measured by the calibration curves. Decision curve analyses (DCA) was used to measure the clinical usefulness. RESULTS: A total of 94 patients were included for analysis. Five independent prognostic factors were identified by LASSO-Cox regression and incorporated into the nomogram: age, the T stage, the absolute counts of peripheral CD3(+)CD4(+) T lymphocytes, CD3(-)CD16(+)CD56(+) NK cells and CD4(+)/CD8(+) ratio. The area under the curve (AUC) values of the predictive model for 5-, 8-, and 10-year overall survival were 0.81, 0.76, and 0.73, respectively. The calibration curves for probability of 5-,8- and 10-year OS showed optimal agreement between nomogram prediction and actual observation. The stratification into different risk groups allowed significant distinction. DCA indicated the good clinical application value of the model. CONCLUSION: We developed a novel nomogram that enables personalized prediction of OS for patients diagnosed with PCa. This finding revealed a relative in age and survival rate in PCa, and a more favorable prognosis in patients exhibiting higher levels of CD4 + T, CD4+/CD8 + ratio and CD3(-)CD16(+)CD56(+) NK cells specifically. This clinically applicable prognostic model exhibits promising predictive capabilities, offering valuable support to clinicians in informed decision-making process.

Clinicopathological features and outcome in elderly patients with idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients. METHODS: A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65-83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People's Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed. RESULTS: Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m2 while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg's stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, p = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, p = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, p < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, p = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, p < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower (p < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment (p < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m2, p = 0.852). CONCLUSIONS: Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg's stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN.

The Long-Term Survival Outcome in Older Patients with Different Pathological Types of Chronic Kidney Disease.

INTRODUCTION: Chronic kidney diseases (CKDs) are prevalent in older people, and renal pathological manifestations are important for diagnosis, treatment, and prognosis. However, the long-term survival outcome and risk factors for older CKD patients with different pathological types are not fully understood and need to be further investigated. METHODS: Medical data were recorded and all-cause mortality was followed up in patients who underwent renal biopsy diagnosed in Guangdong Provincial People's Hospital from 2005 to 2015. Kaplan-Meier analysis was used to identify the incidence of survival outcomes. Multivariate Cox regression models and nomograms were applied to analyze pathological types and other factors for overall survival outcomes. RESULTS: 368 cases were included and the median follow-up was 85 (46.5, 111) months. Overall mortality was 35.6%. The highest mortality was in the mesangioproliferative glomerulonephritis (MPGN) group (88.9%), followed by amyloidosis (AMY) group (84.6%), and the lowest mortality was in the minimal change disease (MCD) group (21.9%). Moreover, multivariate Cox regression model showed that survival times of MPGN {hazard ratio (HR) = 8.215 (95% confidence interval [CI]: 2.735-24.674), p < 0.001} and AMY (HR = 6.130 [95% CI: 2.219-16.94], p < 0.001) were significantly shorter than MCD. In addition, age, lower baseline estimated glomerular filtration rate (eGFR), history of chronic obstructive pulmonary disease (COPD) and cerebrovascular accidents (CVA)/transient ischemic attack (TIA), MPGN, and AMY were independent risk factors for the mortality of older patients with CKD. CONCLUSION: The long-term survival outcome of older CKD patients showed differences among different pathological types, and MPGN, AMY, age, baseline eGFR, CVA/TIA, and COPD were independent predictors for mortality.

Comparison of estimated glomerular filtration rate equations based on serum creatinine-, cystatin C- and creatinine-cystatin C in elderly Chinese patients.

BACKGROUND: This study aimed to further evaluate the accuracy of eleven GFR equations in different subgroups of an elderly Chinese hospitalized population. METHODS: All participants of the study were divided into seven separate groups including age-subgroup, sex-subgroup, GFR Staging-subgroup and whether combined with diabetic, hypertensive, coronary heart disease (CHD) and cerebrovascular disease. Referring to Tc-99m-DTPA dual plasma sample clearance method, six serum creatinine (Cr)-based [Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr), Lund-Malmö Revised (LMR), Berlin Initiative Study (BIS1), Full Age Spectrum (FASCr) and European Kidney Function Consortium (EKFC)], two serum cystatin C(Cys)-based (CKD-EPICys and FASCys), and three Cr-Cys combination based (CKD-EPICr-Cys, BIS2 and FASCr-Cys) equations were employed. Bias, interquartile range of the median difference (IQR), P30, and GFR misclassification rate were calculated to compare the performance of the selected equations. RESULTS: A total of 359 elderly Chinese patients were enrolled. Overall, median mGFR was 36.91(25.26,56.32)ml/min/1.73 m2. Smaller biases (ml/min/1.73 m2) were shown in CKD-EPICr and BIS1 equations (0.75 and 0.61). IQR (ml/min/1.73m2) was least with BIS2 equation and FASCr-Cys equation (10.34 and 10.65). For accuracy (P30), performance of FASCr-Cys, BIS2, and BIS1 equation was superior (78.3%, 78.0%, and 74.7%, respectively). In terms of RMSE (ml/min/1.73 m2), BIS1 and FASCr-Cys equation performed better (12.44 and 12.51). CONCLUSIONS: Overall, this study showed that the eGFR equations were less accurate in the diabetic and non-hypertension group than in the non-diabetic and hypertension group, respectively. Among all enrolled equations, the BIS2 and FASCr-Cys equations might be the best choice to evaluate glomerular filtration rate in Chinese elderly patients.

B lymphocytes subpopulations are associated with cardiac remodeling in elderly patients with advanced chronic kidney disease.

AIM: Chronic Kidney Disease (CKD) is independently associated with increased cardiovascular disease (CVD) risk. The aim of this study was to investigate the potential roles of B lymphocyte populations with cardiac remodeling in elderly patients with advanced CKD. METHODS: We designed a retrospective study in a cohort of 167 patients (84 advanced CKD patients with stage 4-5 and 83 non-CKD controls). B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were identified by flow cytometry. Correlation of B cells subsets with cardiac remodeling and clinical data in elderly CKD patients were analyzed. RESULTS: In this study, we found that the prevalence of hypertension was more common in CKD patients than in the control subjects (P < 0.05). Spearman's analysis showed that CD19(+)CD5(+) B cells were negatively correlated with high sensitivity C-reactive protein (hsCRP), ß2-microglobulin (ß2-MG), serum creatinine (SCr), pro-brain natriuretic peptide (pro-BNP), high-sensitivity troponin T (TNT-hs), left ventricle end-diastolic dimension (LVDD), left ventricle end-systolic dimension (LVSD) and left ventricular mass (LVM), and CD19(+)CD5(-) B cells were negatively correlated with ß2-MG, SCr, pro-BNP and TNT-hs (P < 0.05). In contrary, left ventricular ejection fractions (LVEF) was positively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B cells (P < 0.05). In addition, patients with higher levels of CD19(+)CD5(+) B cells exhibited lower level of pro-BNP, TNT-hs, interventricular septum (IVS), LVSD and LVM (P < 0.05). Higher levels of CD19(+)CD5(-) B cells also presented lower levels of pro-BNP, TNT-hs and LVSD, but higher levels of LVEF (P < 0.05). Cox regression analysis showed that patients with higher levels of LVSD, lower CD19(+)CD5(+)and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05). CONCLUSIONS: Our results showed that CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were negatively correlated with ventricular hypertrophy-related echocardiographic parameters in advanced CKD patients, which indicated that B lymphocytes might be involved in pathogenesis and improve cardiac remodeling in CKD patients.

Decreased B lymphocytes subpopulations are associated with higher atherosclerotic risk in elderly patients with moderate-to-severe chronic kidney diseases.

AIM: Cardiovascular diseases (CVD) are the leading cause of death in patients with chronic kidney disease (CKD), and the risk of CVD increases with reductions in renal function. This study aims to investigate the potential roles of B lymphocyte populations in subclinical atherosclerosis (measured by intima-media thickness, IMT) and prognosis in elderly patients with moderate-to-severe CKD. METHODS: In this study, a total of 219 patients (143 moderate-to-severe CKD patients with stage 3-4 and 76 non-CKD controls) were recruited. B cell subsets: CD19(+)CD5(+) and CD19(+)CD5(-) B cells were analyzed by flow cytometry. Intima-media thickness (IMT) was measured by ultrasound. Correlations between the B cell subsets with IMT and clinical outcome was analyzed. RESULTS: CKD patients showed increased IMT (P = 0.006). The level of CD19(+)CD5(+) and CD19(+)CD5(-) B cells were decreased in CKD patients. Correlation analysis showed that IMT was positively correlated with systolic blood pressure, protein/creatinine ratio and diabetes (P < 0.05), and were negatively correlated with CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes (P < 0.05). Stepwise multiple regression analysis showed that CD19(+)CD5(-) B cells had a significant independent association with IMT (P < 0.05). IMT was increased in lower level of total CD19(+) B cells (≤ 0.06 × 109 /L) and CD19(+)CD5(-) B cells (≤ 0.05 × 109 /L) (P < 0.05). Kaplan-Meier analysis showed that patients with lower levels of CD19(+)CD5(+) and CD19(+)CD5(-) B cells exhibited worse survival (P < 0.05). Cox regression analysis showed that patients with lower CD19(+)CD5(+) and CD19(+)CD5(-) B cells counts have a higher risk of all-cause mortality (P < 0.05). CONCLUSIONS: Our results showed that decreased CD19(+)CD5(+) and CD19(+)CD5(-) B lymphocytes were correlated with atherosclerosis and worse survival, which indicates that B lymphocytes might involve in atherosclerosis and associated the prognosis of elderly patients with moderate-to-severe CKD.

Development of Nickel Selenide@polydopamine Nanocomposites for Magnetic Resonance Imaging Guided NIR-II Photothermal Therapy.

The penetration depth of near-infrared laser has greatly restricted the development of most photothermal agents. Recently, photothermal agents in the second near-infrared (NIR-II) window have drawn great attention as they can overcome above barrier. Herein, a novel "all in one" NIR-II responsive nanoplatform (nickel selenide @polydopamine nanocomposites, NiSe@PDA NCs) based on in situ coating the polydopamine (PDA) on the surface of biomineralized nickel selenide nanoparticles (NiSe NPs) for dual-model imaging-guided photothermal therapy is reported. Under the illumination of NIR-II laser (1064 nm), the photothermal conversion efficiency of NiSe@PDA NCs can reach 48.4%, which is higher than that of single NiSe NPs due to the enhanced molar extinction coefficient. In addition, because of the paramagnetic effect of NiSe NPs, the constructed NiSe@PDA NCs can be acted as T1 contrast agent for magnetic resonance imaging (MRI). Most importantly, the MRI contrast effect is enhanced with the coating of PDA layer due to the loose structure of PDA. Ultimately, both in vitro and in vivo experiments demonstrate that the developed NCs can achieve efficient MRI-guided photothermal therapy for treating malignant tumor. Therefore, the designed NiSe@PDA NCs with excellent features show great potential for clinical MRI-guided cancer therapy.

Precise Subcellular Organelle Targeting for Boosting Endogenous-Stimuli-Mediated Tumor Therapy.

Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and high expression of antioxidant molecules also restrict the efficiency of tumor therapy. As a result, the development of nanoplatforms responsive to endogenous stimuli (such as glucose, acidic pH, cellular redox events, and etc.) has attracted great attention for starvation therapy, ion therapy, prodrug-mediated chemotherapy, or enzyme-catalyzed therapy. In addition, nanomedicines can be modified by some targeted units for precisely locating in subcellular organelles and boosting the destroying of tumor tissue, decreasing the dosage of nanoagents, reducing side effects, and enhancing the therapeutic efficiency. Herein, the properties of the TME, the advantages of endogenous stimuli, and the principles of subcellular-organelle-targeted strategies will be emphasized. Some necessary considerations for the exploitation of precision medicine and clinical translation of multifunctional nanomedicines in the future are also pointed out.

M2 Macrophage Subpopulations in Glomeruli Are Associated With the Deposition of IgG Subclasses and Complements in Primary Membranous Nephropathy.

Objectives: The role of M2 macrophages in the pathogenesis and progression of primary membranous nephropathy (PMN) remains unknown. In this study, we aimed to investigate the relationship between M2 subsets and clinicopathological features of patients with PMN. Methods: A total of 55 patients with PMN confirmed by biopsy were recruited. The clinical and pathological data were recorded, respectively. Immunohistochemistry was used to detect the markers of M2 macrophages, including total macrophages (CD68+), M2a (CD206+), M2b (CD86+) and M2c (CD163+). Results: The numbers of glomerular macrophages, M2a, M2b, and M2c macrophages were 1.83 (1.00, 2.67), 0.65 (0.15, 1.15), 0.67 (0.33, 1.50), and 0.80 (0.05, 2.30) per glomerulus, respectively. Higher number of glomerular macrophages was found in stage II compared with stage III (2.08 vs. 1.16, P = 0.008). These macrophages also were negatively correlated with serum albumin level (r = -0.331, P = 0.014), while positively associated with complement 3 (C3) deposition (r = 0.300, P = 0.026) and the severity of glomerulosclerosis (r = 0.276, P = 0.041). Moreover, glomerular M2a macrophages were significantly correlated with the deposition of C3 (r = 0.300, P = 0.026), immunoglobulin G1 (IgG1) (r = 0.339, P = 0.011), immunoglobulin G2 (IgG2) (r = 0.270, P = 0.046) and immunoglobulin G3 (IgG3) (r = 0.330, P = 0.014) in glomerular basement membrane (GBM). In addition, M2b macrophages were positively associated with IgG1 (r = 0.295, P = 0.029) and IgG2 (r = 0.393, P = 0.003), while M2c macrophages were negatively correlated with complement 4d (C4d) (r = -0.347, P = 0.009) in GBM. Conclusions: Our results showed that M2 macrophage subpopulations in glomeruli are associated with the deposition of IgG subclasses and complements in renal tissue of PMN, which indicate that M2 macrophages may be involved in the pathogenesis and progression of PMN. Moreover, M2a and M2c macrophages might show different tendencies in the pathogenesis of PMN.

Clinical features, risk factors, and clinical burden of acute kidney injury in older adults.

Background: Few epidemiologic studies on acute kidney injury (AKI) have focused on the older adult population. This study investigated the clinical features, risk factors, and clinical burden in this population. Methods: A retrospective observational study was performed with the clinical data of inpatients at Guangdong Geriatrics Institute from 1 August 2012, to 31 December 2016. AKI was classified into community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI), and the risk factors for AKI were ranked by weight. The relationships between AKI and adverse outcomes during hospitalization were analyzed using univariate and multivariate logistic regression. Results: In total, 6126 patients were enrolled, and 1704 patients developed AKI (27.8%): 6.3% had CA-AKI, and 21.5% had HA-AKI. In total, 1425 (23.3%), 202 (3.3%), and 77 (1.3%) patients had stage 1, 2 and 3 AKI, respectively. Age, dementia, moderate/severe renal disease, moderate/severe liver disease, metastatic solid tumor, female sex, congestive heart failure, chronic pulmonary disease, diabetes mellitus with chronic complications, non-metastatic tumor and lymphoma were independent risk factors for HA-AKI. The first five were also independent risk factors for CA-AKI. After multiple adjustment, AKI was associated with intensive care admission (CA-AKI: OR 5.688, 95% CI 3.122-10.361; HA-AKI: OR 4.704, 95% CI 3.023-7.298) and in-hospital mortality (CA-AKI: OR 5.073, 95% CI 2.447-10.517; HA-AKI: OR 13.198, 95% CI 8.133-21.419). Conclusion: AKI occurs in >25% of older adults in the geriatric ward. In addition to traditional risk factors, dementia and tumors were risk factors for AKI in older adults. AKI is closely related to a poor prognosis.

Transcription factor PU.1 and immune cell differentiation (Review).

The transcription factor PU.1, an important member of the ETS family, plays a significant role in the differentiation of immune cells, which include macrophages, neutrophils, dendritic cells, T lymphoid cells, B lymphoid cells and so on. Immune cells are involved in the occurrence and development of diseases, including inflammatory diseases, neoplastic diseases and immune diseases. Therefore, it is particularly crucial to elucidate the roles and mechanisms of PU.1 in immune cells. The elucidation of these mechanisms may lead to the development of more effective therapeutic strategies for the treatment of inflammatory diseases and immune­mediated diseases mediated by various immune cells. With the development of molecular biology, the mechanisms of PU.1 in immune cell differentiation have been further explained. Different levels of PU.1 expression determine the type of immune cell differentiation. PU.1 expression is increased during granulocyte and macrophage differentiation, while it is decreased during T lymphocyte and B lymphocyte differentiation. The present study reviews and discusses the effects of the transcription factor PU.1 on immune cell differentiation.

High glucose contributes to the polarization of peritoneal macrophages to the M2 phenotype in vivo and in vitro.

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and long­term exposure to high glucose is a major contributor to peritoneal fibrosis. Our previous study revealed that M2 macrophages participate in the development of PD­related fibrosis in a rat model. In the present study, the effects of high glucose on peritoneal macrophage polarization in vivo and in vitro were further evaluated. Continuous ambulatory PD (CAPD) patients with an overnight dwell of 1.5 or 2.5% glucose dialysate were recruited for this study. Overnight effluent samples from patients with CAPD (2,000 ml) were centrifuged to collect cells from the peritoneal cavity. J774A.1 cells (murine macrophages from ascites) were cultured in different concentrations of glucose. Macrophage phenotype markers were detected by flow cytometry. The levels of cytokines in PD effluent and the supernatant of murine macrophages were detected by enzyme­linked immunosorbent assays. The activity of arginase was determined by quantitative colorimetric analysis. In total, 107 CAPD subjects (92 patients using 1.5% glucose dialysate and 15 patients using 2.5% glucose dialysate) were recruited. The percentage of M1 macrophages (CD14­ and CCr7­positive cells) in the 1.5 and 2.5% glucose dialysate groups was 23.0±13.3 and 24.9±12.0%, respectively. The difference was not significant (P>0.05). The percentage of M2 macrophages (CD14­ and CD206­positive cells) in the 1.5% glucose dialysate group (36.2±11.4%) was significantly decreased compared to the 2.5% glucose dialysate group (43.2±7.4%) (P<0.05). Murine macrophages were cultured in a high­glucose in vitro environment, and the percentage of M1 macrophages in 138.8 mmol/l glucose medium significantly increased over time. The percentage of M2 macrophages increased in a glucose concentration­dependent and time­dependent manner. Arginase 1 in murine macrophages and the level of transforming growth factor ß1 in the supernatant increased in a glucose concentration­dependent manner. In conclusion, high glucose contributed to the polarization of peritoneal macrophages to the M2 phenotype, which may play an important role in the pathogenesis of PD­related fibrosis.

Decreased B1 and B2 Lymphocytes Are Associated With Mortality in Elderly Patients With Chronic Kidney Diseases.

Aim: Loss of renal function is associated with immune deficiency; however, few studies have addressed the role of B lymphocytes in elderly patients with chronic kidney disease (CKD). In this study, we examined the distribution and the relationship of the B lymphocyte subpopulation with clinical outcomes in elderly CKD patients. Methods: In this study, a total of 380 patients (312 CKD patients and 68 non-CKD controls) were recruited. Venous blood samples were analyzed by flow cytometry to determine the following B cell subsets: total B cells (CD19+), innate B1 cells (CD19+CD5+), and conventional B2 cells (CD19+CD5-). Correlations between the B cell subsets with clinical features and patient prognosis were analyzed. Results: A total of 380 patients (mean age 82.29 ± 6.22 years, 76.3% male) were included. The median follow-up time was 37.0 months (range, 1-109 months); 109 (28.7%) patients died. The main causes of death were infections (59.6%) and cardiovascular diseases (22.9%). Correlation analysis showed that levels of serum creatinine (SCr), blood urea nitrogen (BUN), and CKD were negatively associated with B1 cells. However, lymphocytes, T lymphocytes, and estimated glomerular filtration rate (eGFR) were positively correlated with B1 cells (all P < 0.05). B2 cells were negatively associated with age, SCr, cystatin C, BUN, and CKD, and were positively correlated with hemoglobin, lymphocytes, T lymphocytes, NK cells, and eGFR (all P < 0.05). Patient survival was significantly better in patients with B cells > 0.05 × 109/L, B1 cells > 0.02 × 109/L, and B2 cells > 0.04 × 109/L. Multivariate Cox regression analysis showed that B1 cells > 0.02 × 109/L [hazard ratio (HR) = 0.502, 95% confidence interval (CI): 0.297-0.851, P = 0.010] and B2 cells > 0.04 × 109/L (HR = 0.536, 95% CI: 0.319-0.901, P = 0.019) were independent protective factors for all-cause mortality. Conclusions: Our results showed that B1 and B2 cells exhibited a significantly negative correlation with the progression of CKD in elderly patients. Moreover, B1 and B2 cells were independent prognostic factors for survival, which indicates that the decrease in B cells may be associated with the progression of kidney diseases.

Specific "Unlocking" of a Nanozyme-Based Butterfly Effect To Break the Evolutionary Fitness of Chaotic Tumors.

Chaos and the natural evolution of tumor systems can lead to the failure of tumor therapies. Herein, we demonstrate that iridium oxide nanoparticles (IrOx ) possess acid-activated oxidase and peroxidase-like functions and wide pH-dependent catalase-like properties. The integration of glucose oxidase (GOD) unlocked the oxidase and peroxidase activities of IrOx by the production of gluconic acid from glucose by GOD catalysis in cancer cells, and the produced H2 O2 was converted into O2 to compensate its consumption in GOD catalysis owing to the catalase-like function of the nanozyme, thus resulting in the continual consumption of glucose and the self-supply of substrates to generate superoxide anion and hydroxyl radical. Moreover, IrOx can constantly consume glutathione (GSH) by self-cyclic valence alternation of IrIV and IrIII . These cascade reactions lead to a "butterfly effect" of initial starvation therapy and the subsequent pressure of multiple reactive oxygen species (ROS) to completely break the self-adaption of cancer cells.

Nanomaterials for the regulation of the tumor microenvironment and theranostics.

Cancer has become one of the primary threats to human beings, and traditional therapies (including surgery, chemotherapy and radiotherapy) show limited therapeutic efficacy due to the complexity of tumor biology. Furthermore, determining how to utilize the differences between the tumor microenvironment (TME) and healthy tissues and exploring new nanoplatforms that can realize early diagnosis and effective and non-toxic therapy are challenges in cancer theranostics. Numerous researchers have designed multifunctional nanomaterials and investigated their personalized therapy and regulation abilities toward TME, including oxygen generation, glutathione consumption and the production of reactive oxygen species and multi-model imaging effects. This review will introduce the latest progress in the design of multi-functional nanomedicines for the regulation of TME and their theranostics, and it will provide a critical angle for the future development of nanomedicine.

M2a and M2b macrophages predominate in kidney tissues and M2 subpopulations were associated with the severity of disease of IgAN patients.

M2 macrophages play important roles during the injury and repair phases in kidney. Our aims are to investigate the distribution of M2 subpopulations and the correlation with clinicopathological features of IgA nephropathy (IgAN) patients. In this study, renal samples from 49 IgAN patients were detected by immunofluorescence. The markers of M2 macrophages, including M2a (CD206+/CD68+), M2b (CD86+/CD68+) and M2c (CD163+/CD68+) were identified. We found M2a and M2b macrophages were the predominant subpopulations in kidney tissues of IgAN. M2a macrophages were mainly distributed in tubulointerstitium with renal lesions like segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis. However, there were larger numbers of M2c in glomeruli with minor lesions. Moreover, M2a and M2c macrophages were inversely correlated with the clinical and pathologic features, respectively. These results suggest M2 subpopulations were involved in the progression of IgAN, and M2a and M2c macrophages might show different properties to participate in the pathogenesis of IgAN.

Alternatively Activated Macrophages are Associated with Prostate Volume and Lower Urinary Tract Symptoms Severity of Patients with Benign Prostate Hyperplasia.

BACKGROUND: Recent studies show that alternatively activated macrophages (AAMs) are involved in tissue remodeling and fibrosis. However, the relationship between AAMs and the development of benign prostate hyperplasia (BPH) is unclear. The aim of this study is to investigate the correlation among AAMs, prostate volume, and lower urinary tract symptoms (LUTS) severity of benign prostate hyperplasia (BPH) patients. METHODS: Patients who underwent transurethral incision of the prostate (TUIP) for BPH were recruited and international prostatic symptom scores (IPSS) were assessed before the operations. Patients were divided into two groups: small (< 40 mL) and large prostate (≥ 40 mL) groups. Total macrophages (CD68) and AAMs (co-localization of CD68 and CD206) were analyzed by immunofluorescence. Prostate volume, post-voided residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rate were measured. We compared AAMs and clinical features between groups and analyzed the relationship of AAMs and these clinical parameters. RESULTS: A total of 42 patients diagnosed with BPH were recruited. The numbers of AAMs in prostate tissues of BPH patients with small prostate (n = 20) (5.15 ± 2.32 cells/HP) were significantly lower than those of large prostate (n = 22) (7.73 ± 2.83 cells/HP) (p < 0.05). Moreover, percentages of AAMs (AAMs/total macrophages) of small prostate patients (17.28 ± 6.62%) were lower than those of large prostate patients (23.30 ± 8.66%) (p < 0.05). Pearson's correlation analysis showed the numbers of AAMs were significantly positively correlated with prostate volume (r = 0.509, p < 0.01) and international prostatic symptom score (r = 0.344, p < 0.05). Percentages of AAMs were positively correlated with prostate volume (r = 0.447, p < 0.01). CONCLUSIONS: AAMs are associated the degree of BPH and the severity of LUTS, which indicates that AAMs may play an important role in development of BPH.

[Annular electrode lacrimal duct reconstruction for improving the safety and efficacy of lacrimal stent implantation: a randomized clinical trial].

OBJECTIVE: To evaluate the effect of annular electrode lacrimal duct reconstruction in improving the safety and efficacy of nasolacrimal duct stent implantation for treatment of nasolacrimal duct obstruction. METHODS: This randomized clinical trial was performed to compare the efficacy, success rate of intubation, time used for stent implantation, intraoperative pain, and extubation-assciated complications between nasolacrimal stent implantation with and without annular electrode lacrimal duct reconstruction. RESULTS: A total of 119 eligible patients were enrolled in this trial. The total curative rate at 6 months of follow up after extubation was 70.9% (83/117) in these patients, and was significnatly higher in pateinets with lacrimal duct reconstruction than in those without [80.6% (54/67) vs 58.0% (29/50); χ(2)=7.093, P<0.05]. The total success rate of stent implantation was 98.3% (117/119) in all the patients initially enrolled, and two patients experienced failure of stent implantation and were excluded; the success rate was signfiicantly higher in patients initially enrolled in the lacrimal duct reconstruction group (χ(2)=6.282, P<0.05). The median time required for intubation was shorter in lacrimal duct reconstruction group (12 s vs 33 s; Z=-36.722, P<0.05). The intendity of intraoperative pain was comparable between the two groups (t=0.833, P=0.405). The total rate of puncta injury was 43.6% (51/117) in these patients and similar between the two groups (χ(2)=1.459, P=0.227). The total rate of extubation difficulty was 9.4% (11/117) in all the patients, and was lower in lacrimal duct reconstruction group [4.5% (3/67) vs 16% (8/50); χ(2)=4.463, P<0.05]. Stent breakage in extubation occurred in 4.3% (11/117) of the patients with similar rates between the two groups (χ(2)=2.964, P=0.085). Spearman bivariate correlation analysis showed that the time required for intubation was inversely correlated with the treatment efficacy (r=-0.584, P<0.05) and positively with the occurrence of extubation difficulty (r=0.491, P<0.05); extubation difficulty was inversely correlated with the curative effect (r=-0.511, P<0.05). CONCLUSION: Annular electrode nasolacrimal duct reconstruction can increase the safety and efficacy of nasolacrimal duct stent implantation for treatment of nasolacrimal duct obstruction.

Alternatively activated macrophages are associated with metastasis and poor prognosis in prostate adenocarcinoma.

Recent studies have revealed that alternatively activated macrophages (AAMs) are involved in tumor progression. However, the effect of AAMs on the metastasis of prostate cancer is poorly understood. In the present study, the prostate tissues of 42 patients with prostate adenocarcinoma (PCa) were used in the analysis of tumor associated macrophages (TAMs) and AAMs by immunofluorescence. The patients were followed up for 5 years. The associations of TAMs and AAMs with the clinicopathological features and outcome in these cases were evaluated. Immunofluorescent analysis indicated that the mean number of TAMs (CD68-positive cells) in the prostate tissues of PCa patients with metastasis [45.29±7.25 cells/high-power field (HPF)] was significantly higher compared with that of PCa patients without metastasis (33.57±5.25 cells/HPF; P<0.01). The mean numbers of AAMs (CD68- and CD206-positive cells) in the tissues of PCa patients with and without metastasis were 29.43±5.68 and 9.14±5.29 cells/HPF, respectively. In addition, the percentage of AAMs (number of AAMs/number of TAMs) was 65.11±9.68 and 27.32±7.85% in patients with and without metastasis, respectively. The differences in the number and percentage of AAMs between the two groups were statistically significant (P<0.01). The number and percentage of AAMs was positively correlated with tumor grade and serum prostate-specific antigen (PSA) level. Univariate analysis indicated that the level of PSA, Gleason score, metastatic status, T grade, number of TAMs, number of AAMs and percentage of AAMs were predictors of the overall survival. Furthermore, multivariate analyses revealed that Gleason score, level of PSA and number of TAMs were predictors for overall survival rate. These results indicate that TAMs and AAMs may be important in the metastasis of PCa, and that TAMs and AAMs may be used as potential biomarkers of poor prognosis in late-stage PCa patients.

A retrospective analysis of kidney function and risk factors by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese patients.

Chronic kidney disease accounts for much of the increased mortality, especially in the elder population. The prevalence of this disease is expected to increase significantly as the society ages. Our aim was to evaluate the kidney function and risk factors of reduced renal function among elderly Chinese patients. This study retrospectively collected clinical data from a total of 1062 inpatients aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function and risk factors were also analyzed. For all 1062 subjects, the mean eGFR was 71.0 ± 24.8 mL/min/1.73 m(2), and the incidence rates of reduced renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6% and 8.7%, respectively. The eGFR values were 83.4 ± 28.4, 72.2 ± 22.9, 67.8 ± 24.3 and 58.8 ± 29.1 mL/min/1.73 m(2) in the groups of 60-69, 70-79, 80-89 and ≥90 years age group (F = 15.101, p = 0.000), respectively; while the incidences of reduced renal function were 12.8%, 27.0%, 37.8% and 51.7% (χ(2) = 36.143, p = 0.000). Binary logistic regression analysis showed that hyperuricemia (OR = 4.62, p = 0.000), proteinuria (OR = 3.96, p = 0.000), urinary tumor (OR = 2.92, p = 0.015), anemia (OR = 2.45, p = 0.000), stroke (OR = 1.96, p = 0.000), hypertension (OR = 1.83, p = 0.006), renal cyst (OR = 1.64, p = 0.018), female (OR = 1.54, p = 0.015), coronary artery disease (OR = 1.53, p = 0.008) and age (OR = 1.05, p = 0.000) were the risk factors of reduced renal function. In conclusion, eGFR values decreased by age, while the incidence of reduced renal function, proteinuria, hematuria and leukocyturia increased with age. Treatment and control of comorbidities may slow the decline of renal function in elderly patients.