Combination of Rituximab and Low-dose Tacrolimus in the Treatment of Refractory Membranous Nephropathy: A Retrospective Cohort Study

Background: Conventional regimens for refractory idiopathic membranous nephropathy (IMN) still have limitations. Rituximab (RTX) has a good effect in the treatment of refractory IMN. However, whether RTX single or combined with immunosuppressive therapy is more effective and whether adverse events will increase are still inconclusive. Aims: To investigate the efficacy and safety of RTX combined with low-dose tacrolimus (TAC) versus RTX alone in the treatment of refractory IMN. Study Design: A retrospective cohort study. Methods: We retrospectively studied 91 cases of refractory IMN diagnosed between January 2018 and June 2021, all of which immunosuppressive regimens had failed. Thirty-four patients received RTX combined with TAC (RTX + TAC group), and 57 patients were treated with RTX alone (RTX group). The RTX + TAC group was given RTX 1 g once every 2 weeks, two times, and TAC 0.03 mg/kg/day orally. In the RTX group, RTX was given at the same dosage as the RTX + TAC group. Clinical data were collected at 12 months of follow-up to compare the complete and partial remission rates and the incidence of adverse reactions between the two groups. Results: The overall effectiveness rate of RTX + TAC in the treatment of refractory IMN was 87.14%, of which the partial and complete remission rates were 50.01% and 37.13%, respectively, and the median time to complete remission was 9 (interquartile range [IQR] 6.0, 12.0) months. The overall effectiveness rate of RTX was 65.87%, of which the partial and complete remission rates were 39.48% and 26.39%, respectively, and the median time to complete remission was 10.5 (IQR 6.0, 12.0) months. Adverse events occurred in 6 (17.65%) patients in the RTX + TAC group and in 11 (19.30%) in the RTX group (P = 0.473). Proteinuria and high titer of PLA2R are risk factors for non-remission. Conclusion: The complete and partial remission rates of RTX combined with low-dose TAC in the treatment of refractory IMN are higher than those of RTX alone, and no significant increase in adverse events was noted.

STAT1 mediates cellular senescence induced by angiotensin II and H2O2 in human glomerular mesangial cells.

Human glomerular mesangial cells (HMCs) have a finite lifespan and eventually enter irreversible growth arrest known as cellular senescence which is thought to contribute to kidney aging and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMCs senescence still remains to be explored. In our study, induction of Angiotensin II (Ang II) and H(2)O(2) accelerated premature senescence of HMCs as confirmed by increased senescence-associated -ß-galactosidase (SA-ß-gal) positive staining cells and G0/G1 cell cycle arrest. The STAT1 and STAT3 activity and the expression of p53 and p21(Cip1) were increased after Angiotensin II and H(2)O(2) treatment. Knockdown STAT1 using RNA interference significantly attenuated the progression of HMCs senescence, decreased the elevated p53 and p21(Cip1), more interestingly, STAT3 and its activity was further enhanced while STAT1 was silenced. Our results indicate that STAT1 might mediate Ang II and H(2)O(2)-induced HMCs senescence through p53/p21(Cip1) pathway and the relative abundance of STAT1 and STAT3.

Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence.

Human glomerular mesangial cells (HMCs) have a finite lifespan, and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders, such as chronic kidney disease. The signal transducer and activator of transcription 1 (STAT1) is a latent transcription factor involved in a variety of signal transduction pathways, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, the induction of angiotensin II (Ang II)-accelerated HMC senescence, as judged by increased senescence-associated ß-galactosidase (SA-ß-gal)-positive staining cells, morphological changes, and G0/G1 cell cycle arrest. STAT1 activity and the expression of p53 and p21(Cip1) were increased after Ang II treatment. STAT1 knockdown using RNA interference significantly inhibited the progression of HMC senescence and decreased the elevated expression of p53 and p21(Cip1). Pretreating HMCs with Ang II receptor blocker losartan also inhibited the progression of HMC senescence and STAT1 activity. Our results indicate that STAT1 is implicated in the mediation of Ang II-induced HMC senescence through p53/ p21(Cip1) pathway, and that losartan could attenuate HMC senescence by regulating STAT1. The antioxidant N-acetyl-L-cysteine reduced ROS production and STAT1 activity induced by Ang II, indicating that Ang II uses ROS as a second messenger to regulate STAT1 activity.

Clinical features of acute focal bacterial nephritis in adults.

Acute focal bacterial nephritis (AFBN) is a localized bacterial infection of the kidneys presenting as an inflammatory mass that can develop into renal abscess. The current reports on AFBN mostly are among children and rarely described in adults. This study was aimed to analyze the clinical features of AFBN in adults and make a review for the disease to give the clinicians some clues to suspect and recognize it in adults. From January 2014 to December 2019, AFBN was diagnosed by contrast-enhanced computed tomography (CT) in 238 adults at the Department of Nephrology, the Second Hospital of Hebei Medical University, Shijiazhuang, China. We reviewed the clinical records of these patients and asked them about their post-discharge status via telephone follow-up. Of all the patients, 195 were female and 43 were male, the median age were 46.87 years. 86.13% presented with fever, 55.89% presented with lower urinary tract symptoms and 97.9% presented with pyuria. In renal ultrasonography, abdominal findings were seen only 22.69% patients. E.coli accounted for 74.73% of the isolated pathogen. After 4 weeks of treatment, the patients had no recurrence of symptoms. We recommend that when a patient presents clinically with acute pyelonephritis, but the fever persist longer after antimicrobial treatment (≥ 4 days in our study), AFBN should be suspected. For the diagnosis, contrast-enhanced CT is the "gold standard", magnetic resonance imaging (MRI) may be a good option, but the ultrasonography is probably not satisfied. 3-4 weeks of antibiotic therapy may be appropriate for AFBN in adults.

2,2'-Dihydroxy-4,4'-dimethoxy-benzophenon as Bifunctional Additives for Passivated Defects and Improved Photostability of Efficient Perovskite Photovoltaics.

Organic-inorganic hybrid perovskite solar cells (PSCs) have developed rapidly in the past decade, but their commercial applications are restricted by further improvement in their photovoltaic performance and stability. Herein, we propose a facile and effective method employing 2,2'-dihydroxy-4,4'-dimethoxy-benzophenon (BP6) as bifunctional additive to construct efficient and photostable PSCs. BP6, as an additive, improves the crystallization quality of perovskite absorbers and further inhibits defect-mediated non-radiative recombination through interaction between the C═O group and defects; as a UV absorber, BP6 protects the PSCs from UV degradation by effectively absorbing UV light through molecular tautomerism under continuous strong UV irradiation. Eventually, the champion PSC demonstrates an efficiency of 22.85% with enhanced UV stability after addition of 0.024 wt % BP6. These results reveal that addition of UV absorbers (such as BP6 in this study) is a simple and effective strategy to fabricate efficient and photostable PSCs.

Manipulated Crystallization and Passivated Defects for Efficient Perovskite Solar Cells via Addition of Ammonium Iodide.

Organic-inorganic metal halide perovskite materials have been widely studied as the light absorber for efficient photovoltaics. However, perovskite layers with defective nature are typically prepared with an uncontrollable crystallization process, intrinsically limiting further advance in device performance, and thus require delicate manipulation of crystallization processes and defect density. Here, we demonstrate an ammonium-assisted crystallization of perovskite absorbers during a two-step deposition to fabricate efficient solar cells. Addition of ammonium iodide (NH4I) is devised to manipulate the nucleation and crystal growth of perovskite, wherein the formation and transition of intermediate x[NH4+]•[PbI3]x- enables high-quality perovskite layers with an enlarged grain and reduced defect density. As a result, the perovskite solar cells (PSCs) achieve an average efficiency of 21.36% with a champion efficiency of 22.15% and improved environmental stability over 30 days in ambient conditions with varied relative humidity. These results with addition of NH4I provide an available and ingenious way to construct high-quality perovskite layers for efficient solar cells and will advance the commercial application of perovskite-based photovoltaics.

[Effect of budesonide on the heme oxygenase-1 expression in lung tissues of rats with asthma].

OBJECTIVE: To study the expression of heme oxygenase-1 (HO-1) gene and protein and the effect of budesonide (BUD) on the HO-1 expression in lung tissues in rats with asthma. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups: normal control, asthma model, dexamethasone (DXM)-, hemin (HO-1 challenger)-or BUD-treated asthma. The asthma model was prepared by ovalbumin sensitization and challenge. The rats were sacrificed 24 hrs after the last challenge. The blood COHb content,and the total cell count and the percentage of differential cells in bronchoalveolar lavage fluid (BALF) were measured. The expression of HO-1 protein and mRNA in lung tissues was detected with immunohistochemistry and RT-PCR, respectively. The airway inflammation situations were evaluated by histopathology. RESULTS: The airway inflammatory cell infiltration in the DXM-, hemin- and BUD-treated asthma groups was remarkably alleviated compared with that in the asthma model group. Compared with the normal control group, the expression of HO-1 mRNA and protein in lung tissues and the blood COHb content in the asthma model and the DXM-, hemin- and BUD-treated asthma groups were significantly up-regulated. The DXM-, hemin- and BUD-treated asthma groups showed significantly increased expression of HO-1 protein and mRNA in lung tissues compared with the asthma model group. The blood COHb content in the DXM-and the hemin-treated asthma groups was significantly higher than that in the asthma model group. CONCLUSIONS: The expression of HO-1 protein and mRNA in lung tissues and blood HO-1 activity increased in rats with asthma,suggesting that HO-1 may be involved in the pathogenesis of asthma. HO-1 may have a protective effect against the airway inflammation in asthmatic rats. BUD and DXM can up-regulate the expression of HO-1 protein and mRNA, thus providing protective effects against the airway inflammation in asthmatic rats.

Hypertension Control in Adults With CKD in China: Baseline Results From the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

BACKGROUND: Hypertension contributes to increased morbidity and mortality in the chronic kidney disease (CKD) population. Studies on blood pressure control in CKD patients in China are limited. In this study, we aimed to describe the status of blood pressure control in Chinese CKD patients based on the first national prospective CKD cohort data. METHODS: A subgroup of Chinese Cohort Study of Chronic Kidney Disease participants with hypertension at baseline was included in the present study. Uncontrolled blood pressure was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. Defined daily doses (DDDs) are used as a standard measurement of drug utilization in this population. Factors associated with uncontrolled blood pressure were analyzed using multivariable logistic regression. RESULTS: There were 2,251 hypertensive CKD subjects among 2,873 predialysis CKD participants. The awareness, treatment, and control rates of hypertension were 80.7%, 95.6%, and 57.1%, respectively. Factors independently associated with uncontrolled blood pressure were overweight, obesity, albuminuria, decreased estimated glomerular filtration rate (eGFR), and diabetes. Over 50% of study subjects were prescribed 2 or more antihypertensive medications and only 7% were prescribed diuretics. Uncontrolled hypertensive patients were prescribed less antihypertensive medication than controlled hypertensives (DDD 1.3 [1.0-2.3] vs. 2.0 [1.0-3.1], P < 0.001). CONCLUSIONS: Hypertension control was suboptimal among hypertensive CKD patients in China, especially among those overweight or with obesity, albuminuria, lower eGFR, and diabetes. Patients with uncontrolled hypertension should undergo treatment regimen evaluation to select the appropriate dosage and type of antihypertensive medications.

Picroside II protects cardiomyocytes from hypoxia/reoxygenation-induced apoptosis by activating the PI3K/Akt and CREB pathways.

Picroside II, an iridoid glucoside found in the root of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae), has been demonstrated to reduce apoptosis in neuronal cells and other cell types. However, whether picroside II has a protective effect against cardiomyocyte apoptosis is poorly understood. In the present study, we investigated the cardioprotective role of picroside II and the underlying mechanisms in hypoxia/reoxygenation-induced cardiomyocyte apoptosis. The pretreatment with picroside II markedly attenuated hypoxia/reoxygenation-induced cell damage dose-dependently, which was evident by the increased cell viability and the corresponding decrease in lactate dehydrogenase release (LDH). The pretreatment with picroside II inhibited apoptosis confirmed by Annexin V-FITC staining, Hoechst 33258 nuclear staining and by assessment of caspase-3 activity. In addition, we found that picroside II not only increased the expression of Bcl-2, while decreasing Bax expression, but also augmented Akt and cAMP response element-binding protein (CREB) phosphorylation and ultimately inhibited hypoxia/reoxygenation-induced apoptosis. Furthermore, the protective effects of picroside II were abrogated by pretreatment of the cells with wortmannin or LY294002, a specific PI3K inhibitor. The present study suggests that picroside II inhibits hypoxia/reoxygenation-induced apoptosis in cardiomyocytes by activating the PI3K/Akt and CREB pathways and modulating expression of Bcl-2 and Bax.