Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial / Association of serum uric acid with benefits of intensive blood pressure control

Introducción y objetivos: El control intensivo de la presión arterial sistólica (PAS) mejora los resultados de la estrategia de control de la presión arterial en el ensayo STEP con pacientes ancianos hipertensos. Sin embargo, se desconoce si los niveles de ácido úrico pueden afectar los beneficios del control intensivo de la PAS. Métodos: El ensayo STEP fue un estudio controlado y aleatorizado que comparó el efecto del control intensivo (PAS objetivo de 110 o <130mm Hg) frente al tratamiento estándar (PAS objetivo de 130 o <150mm Hg) de la PAS en pacientes chinos hipertensos de entre 60 y 80 años. El objetivo primario incluyó un conjunto de eventos asociados a la enfermedad cardiovascular. Se utilizaron los modelos de curvas spline cúbicas restringidas y análisis de subgrupos para estudiar si los efectos del control intensivo de la PAS difieren en función las concentraciones basales de ácido úrico. Ambos modelos se basaron en la subdistribución de riesgos de Fine-Gray para el análisis del objetivo primario y los objetivos secundarios. El modelo de regresión de Cox se utilizó para el análisis de muerte por cualquier causa. También se analizaron las concentraciones de ácido úrico durante el seguimiento. Resultados: El riesgo del objetivo primario se incrementó con el incremento de la concentración de ácido úrico tanto en el grupo de tratamiento intensivo como en el de tratamiento estándar. Los pacientes bajo tratamiento intensivo mostraron menor subdistribución (ajustada de forma multivariable) del cociente de riesgo para el objetivo primario, aunque con un amplio solapamiento del IC 95%. La estratificación de pacientes por terciles de concentración de ácido úrico mostró un CR de 0,55 (IC95%, 0,36-0,86; p=0,008) para el tercil 1 (ácido úrico <303,0μmol/l), de 0,80 (IC95%, 0.56-1.14; p=0,22) para el tercil 2 (AcU 303,0 a <375,8μmol/l) y de 0,86 (IC95%, 0,60–1,21; p=0,39) para el tercil 3 (AcU ≥ 375,8μmol/l); p=0,29 para la interacción...(AU)

Introduction and objectives: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. Methods: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. Results: Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends...(AU)

[Correlation Between the Diversity Characteristics of Groundwater Bacterial Community and Environmental Factors in Typical Industrial Areas].

In order to investigate the composition and diversity of groundwater bacterial communities in typical industrial areas in Shanghai, the Illumina MiSeq high-throughput technology was adopted to explore the correlation and response mechanism of groundwater bacterial communities and environmental factors in typical industries, combined with the analysis of groundwater tri-nitrogen, heavy metals, organic matter, and other indicators. The results showed that the ammonia nitrogen in the groundwater of the petrochemical industry was 64.49%, 32.46%, and 113.91% higher than that of the textile industry, metal products industry, and other industries (P<0.05), respectively. The main detectable indicators of organic matter were total petroleum hydrocarbons (TPH) and volatile phenol. The mass concentration of volatile phenol in groundwater of the petrochemical industry was significantly higher than that of the textile industry, metal products industry, and other industries (P<0.05). The mass concentration of arsenic in the metal products industry was 49.26% and 50.59% higher than that in the petrochemical industry and other industries (P<0.05), respectively. Chloride, manganese, sulfate, etc., were significantly different in different industries (P<0.05). The Shannon index of groundwater in the textile industry was the highest at 3.14, whereas the Shannon index and Ace index of the groundwater in the metal products industry were as low as at 2.42 and 960.46, respectively. The dominant bacterial phylum in groundwater in the industrial area was Proteobacteria, accounting for 80.05%-86.18%. Arsenic, mercury, TPH, etc. were the main influencing factors in groundwater in industrial areas, whereas the nitrifying bacteria, denitrifying bacteria, and organic matter-degrading bacteria were mostly related to groundwater environmental factors. The results of this study can provide theoretical support for groundwater pollution risk management and microbial remediation in petrochemical and metal product industrial areas.

Corrosion Behavior and Bio-Functions of the Ultrafine-Grained Ti6Al4V-5Cu Alloy with a Dual-Phase Honeycomb Shell Structure in Simulated Body Fluid.

Titanium alloys are widely used in biomedical applications. However, cases of implant failure due to fatigue fracture and bacterial infection are common. In addition, implants are susceptible to metal ions (Al, V) released by long-term exposure to human body fluids, which causes neuropathy, mental disorders, and other diseases. Thus, development of novel materials to achieve long-term safety of implants is currently a research hotspot. Recently, our research group has developed an ultrafine-grained Ti6Al4V-5Cu alloy with a unique "dual-phase honeycomb shell" (DPHS) structure, which possesses high fatigue strength and stability. This study further affirmed its higher corrosion behavior, antibacterial properties, and cytocompatibility compared to the coarse-grained Ti6Al4V and Ti6Al4V-5Cu alloys. The ultrafine-grained structure of Ti6Al4V-5Cu having DPHS increased the proportion of phases (Cu-rich phases, ß-phase, and Ti2Cu intermetallic phase) with a lower surface potential. It was observed that the developed microstructure was conducive to a stable configuration of the oxide (passive) layer on the alloy surface. In addition, the low-phase interfacial energies of the ultrafine-grained structure with DPHS even facilitated the improvement of the denseness of the protective passive film and eventually enhanced the corrosion behavior. Besides, the fine-Cu-rich phases and the micro-galvanic couples formed between them and the matrix significantly increased the contact frequency of bacteria, thus increasing the contact sterilization efficiency of the ultrafine-grained Ti6Al4V-5Cu alloy. These results showed that the new ultrafine-grained Ti6Al4V-5Cu alloy has excellent corrosion resistance and biological functions for clinical application.

Association of serum uric acid with benefits of intensive blood pressure control.

INTRODUCTION AND OBJECTIVES: Intensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. METHODS: The STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. RESULTS: Overall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0µmol/L; tertile 2 [T2], 303.0 to <375.8µmol/L; and tertile 3 [T3], ≥375.8µmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36-0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56-1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60-1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. CONCLUSIONS: There was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Hub genes for early diagnosis and therapy of adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a subtype of craniopharyngioma, a neoplastic disease with a benign pathological phenotype but a poor prognosis in the sellar region. The disease has been considered the most common congenital tumor in the skull. Therefore, this article aims to identify hub genes that might serve as genetic markers of diagnosis, treatment, and prognosis of ACP. METHODS: The procedure of this research includes the acquisition of public data, identification and functional annotation of differentially expressed genes (DEGs), construction and analysis of protein-protein interaction network, and the mining and analysis of hub genes by Spearman-rho test, multivariable linear regression, and receiver operator characteristic curve analysis. Quantitative real-time polymerase chain reaction was used to detect the level of mRNA of relative genes. RESULTS: Among 2 datasets, a total of 703 DEGs were identified, mainly enriched in chemical synaptic transmission, cell adhesion, odontogenesis of the dentin-containing tooth, cell junction, extracellular region, extracellular space, structural molecule activity, and structural constituent of cytoskeleton. The protein-protein interaction network was composed of 4379 edges and 589 nodes. Its significant module had 10 hub genes, and SYN1, SYP, and GRIA2 were significantly down-regulated with ACP. CONCLUSION: In a word, we find out the DEGs between ACP patients and standard samples, which are likely to play an essential role in the development of ACP. At the same time, these DEGs are of great value in tumors' diagnosis and targeted therapy and could even be mined as biological molecular targets for diagnosing and treating ACP patients.

Application and prospects of high-throughput screening for in vitro neurogenesis.

Over the past few decades, high-throughput screening (HTS) has made great contributions to new drug discovery. HTS technology is equipped with higher throughput, minimized platforms, more automated and computerized operating systems, more efficient and sensitive detection devices, and rapid data processing systems. At the same time, in vitro neurogenesis is gradually becoming important in establishing models to investigate the mechanisms of neural disease or deve lopmental processes. However, challenges remain in generating more mature and functional neurons with specific subtypes and in establishing robust and standardized three-dimensional (3D) in vitro models with neural cells cultured in 3D matrices or organoids representing specific brain regions. Here, we review the applications of HTS technologies on in vitro neurogenesis, especially aiming at identifying the essential genes, chemical small molecules and adaptive microenvironments that hold great prospects for generating functional neurons or more reproductive and homogeneous 3D organoids. We also discuss the developmental tendency of HTS technology, e.g., so-called next-generation screening, which utilizes 3D organoid-based screening combined with microfluidic devices to narrow the gap between in vitro models and in vivo situations both physiologically and pathologically.

Lipids associated with plant-bacteria interaction identified using a metabolomics approach in an Arabidopsis thaliana model.

Background: Systemic acquired resistance (SAR) protects plants against a wide variety of pathogens. In recent decades, numerous studies have focused on the induction of SAR, but its molecular mechanisms remain largely unknown. Methods: We used a metabolomics approach based on ultra-high-performance liquid chromatographic (UPLC) and mass spectrometric (MS) techniques to identify SAR-related lipid metabolites in an Arabidopsis thaliana model. Multiple statistical analyses were used to identify the differentially regulated metabolites. Results: Numerous lipids were implicated as potential factors in both plant basal resistance and SAR; these include species of phosphatidic acid (PA), monogalactosyldiacylglycerol (MGDG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TG). Conclusions: Our findings indicate that lipids accumulated in both local and systemic leaves, while other lipids only accumulated in local leaves or in systemic leaves. PA (16:0_18:2), PE (34:5) and PE (16:0_18:2) had higher levels in both local leaves inoculated with Psm ES4326 or Psm avrRpm1 and systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326. PC (32:5) had high levels in leaves inoculated with Psm ES4326. Other differentially regulated metabolites, including PA (18:2_18:2), PA (16:0_18:3), PA (18:3_18:2), PE (16:0_18:3), PE (16:1_16:1), PE (34:4) and TGs showed higher levels in systemic leaves of the plants locally infected with Psm avrRpm1 or Psm ES4326. These findings will help direct future studies on the molecular mechanisms of SAR.

[Pollution Characteristic and Control Factor Analysis of Atmospheric Ozone During Summer Typical Periods in Linyi, Shandong].

In June 2020, an observation experiment of O3 and its precursors was carried out in Linyi City, Shandong Province. Based on the observation data and MCM photochemical model simulation, the formation mechanism and control mechanism of an ozone pollution case in mid-June were analyzed. The study found that, despite the high precipitation during the observation period, ozone concentrations rapidly accumulated and exceeded the limits once the weather cleared, with the 1-h average and 8-h φ (O3) exceeding the national ambient air quality standards on 10 days (32% in frequency)and 14 days (45%), respectively. The diurnal variation in O3 concentration was unimodal and accompanied by the afternoon peak at 16:00. MCM simulation results showed that the daily net reaction rate of O3 was 20×10-9 h-1, and HO2·+NO and RO2·(except CH3O2·)+NO contributed 49.0%-51.1% and 37.3%-40.2% of O3 generation, respectively. The contribution of the·OH+NO2 reaction to the total consumption of O3 was 35.1%-57.4%. The results of VOCs reactivity, relative incremental reactivity (RIR), and the EKMA curve method showed that the generation of O3 was more sensitive to alkenes (mainly trans-2-pentene and trans-2-butene)and aromatics (mainly m/p-xylene and toluene)but was negatively sensitive to NOx. In other words, the reduction in VOCs concentration would lead to the decrease in O3 concentration, whereas the reduction in NOx concentration would lead to the increase in O3 concentration. PMF source analysis results showed that volatile sources used by solvents and vehicle exhaust emissions contributed significantly to the above key precursor VOC species. Considering the titration effect of NO from vehicle exhaust emissions on ozone, controlling the use of volatile sources of solvents can realize the control of O3 pollution accurately and efficiently.

[Effects of surface and mixed application of sewage sludge on Neolamarckia cadamba root growth]. / è¡¨æ–½å’Œæ··æ–½æ±¡æ³¥å¯¹å›¢èŠ±æ ¹ç³»ç”Ÿé•¿çš„å½±å“.

The utilization of sewage sludge in forests is an important way of recycling. However, the effect of sewage sludge application on woody plant root growth has been rarely reported. The effects of surface application and mixed application of sewage sludge (mass ratio in 10%) on the dynamics in root morphology of a fast-growing tree species (Neolamarckia cadamba), soil pH, electric conductivity, and heavy metal content of roots in different soil layers were analyzed by a rhizobox experiment. The relationship between root length and soil pH value, electric conducti-vity, and root heavy metal content were further analyzed. Results showed that mixed application of sewage sludge inhibited root length, root surface area, and root volume. After 120 and 240 days of mixed application, total root length in the 0-20 cm soil layer was 76.9% and 67.4% of that of no sewage sludge application, respectively. Surface application of sewage sludge did not affect root length and root surface area but increased root volume. The mixed application of sewage sludge significantly increased soil pH, electric conductivity, and root heavy metal content. Root Cd contents in 0-20 cm and 20-40 cm soil layers with the mixed application of sewage sludge were 11.5 and 10.0 times as that of no sewage sludge application, respectively. Soil electric conductivity had a significant nega-tive correlation with root length in 0-20 cm soil layer among different treatments. Root Cd content had a significant negative correlation with root length in both the surface and the mixed applications of sewage sludge. These results indicated that mixed application of sewage sludge could inhibit N. cadamba root growth mainly by increasing soil electric conductivity and root Cd content, while the surface application of sewage sludge did not affect root growth.

Prognosis of Oligodendroglioma Patients Stratified by Age: A SEER Population-Based Analysis.

PURPOSE: Glioma may affect patients of any age. So far, only a limited number of big data studies have been conducted concerning oligodendroglioma (OG) in diverse age groups. This study evaluated the risk factors for OG in different age groups using the Surveillance, Epidemiology, and End Results (SEER) database built by the National Cancer Institute, which is part of the National Institutes of Health. PATIENTS AND METHODS: A total of 5437 cases within the SEER database were included. These patients were divided into seven age groups. The Kaplan-Meier method was employed for survival analysis. The independent risk factors for the survival of OG patients were identified using the Cox regression model. A nomogram was drawn with R software based on the independent risk factors. The X-tile software was adopted to find the optimal age group at diagnosis. RESULTS: The all-cause mortality and the tumor-specific mortality increased with age. The univariate analysis showed that the patients' age, gender, primary lesion location, side affected by the primary lesion (left or right), surgery for the primary lesion, and tumor size were correlated with survival (P<0.05). Multivariate Cox regression analysis showed that age was an independent risk factor for the survival of OG patients (P<0.05). The optimal cutoff value of age in terms of overall survival (OS) and cause-specific survival (CSS) were identified as 48 and 61 years and 48 and 59 years, respectively. CONCLUSION: The older the age, the worse the survival would be. That's, the mortality increased with age. In the clinic, healthcare professionals should be fully aware of the variability in the prognosis of OG patients in different age groups. Therefore, individualized treatments are recommended to OG patients in different age groups to optimize the prognosis.

Two new species of the genus Latouchia Pocock, 1901 from southeast China (Araneae: Mygalomorphae: Halonoproctidae).

BACKGROUND: The genus Latouchia Pocock, 1901 (Araneae: Mygalomorphae: Halonoproctidae: Ummidiinae) includes 21 species and 1 subspecies occurring in southeast Eurasia. Just like other trapdoor spiders, the specimens of Latouchia are rare in collections, unless from targeted collecting. NEW INFORMATION: Two new species of mygalomorph spiders, Latouchiarufa sp. n. from Guangdong, China and L.yejiei sp. n. from Hainan, China, are described and illustrated from both sexes. Diagnostic characters of the two species are provided.

Roles of Endogenous Melatonin in Resistance to Botrytis cinerea Infection in an Arabidopsis Model.

Melatonin is an important bioactive molecule in plants. Two synthetases, N-acetylserotonin methyltransferase (ASMT) and serotonin N-acetyltransferase (SNAT) are involved in the final two steps of melatonin synthesis. Melatonin participates in responses to a variety of biotic and abiotic stresses in plants, but few studies have addressed the roles of endogenous melatonin in pathogen resistance. We investigated the role of endogenous melatonin in resistance to Botrytis cinerea infection in an Arabidopsis thaliana model system. Plant lines that overexpressed ASMT or SNAT through genetic manipulation showed upregulated expression of resistance genes PR1 and PR5, transcription factor gene WRKY33, and jasmonic acid (JA) defense pathway marker gene PDF1.2, and downregulated transcription factor gene MYC2 in JA signaling pathway. Higher melatonin content also enhanced the activity of antioxidant enzymes superoxide dismutase (SOD) and peroxidase (POD), increased JA content, reduced plant disease symptoms, and reduced lesion size in leaves. These findings indicate that endogenous melatonin enhances plant resistance to B. cinerea infection. In contrast, ASMT and SNAT gene silencing lines showed opposite results and were more susceptible to B. cinerea. Thus, it can be demonstrated that melatonin functions as an effective regulator of plant stress resistance at the genetic level. A schematic model is presented for its role in resistance to B. cinerea infection. Our findings also helped to elucidate the associated signal transduction pathways and interactions between melatonin and other plant hormones.

Hub biomarkers for the diagnosis and treatment of glioblastoma based on microarray technology.

BACKGROUND: Glioblastoma (GBM) is the most common clinical intracranial malignancy worldwide, and the most common supratentorial tumor in adults. GBM mainly causes damage to the brain tissue, which can be fatal. This research explored potential gene targets for the diagnosis and treatment of GBM using bioinformatic technology. METHODS: Public data from patients with GBM and controls were downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified by Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus 2R (GEO2R). Construction of the protein-protein interaction network and the identification of a significant module were performed. Subsequently, hub genes were identified, and their expression was examined and compared by real-time quantitative (RT-q)PCR between patients with GBM and controls. RESULTS: GSE122498 (GPL570 platform), GSE104291 (GPL570 platform), GSE78703_DMSO (GPL15207 platform), and GSE78703_LXR (GPL15207 platform) datasets were obtained from the GEO. A total of 130 DEGs and 10 hub genes were identified by GEPIA and GEO2R between patients with GBM and controls. Of these, strong connections were identified in correlation analysis between CCNB1, CDC6, KIF23, and KIF20A. RT-qPCR showed that all 4 of these genes were expressed at significantly higher levels in patients with GBM compared with controls. CONCLUSIONS: The hub genes CCNB1, CDC6, KIF23, and KIF20A are potential biomarkers for the diagnosis and treatment of GBM.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a newly recognized rare disease. The renal pathology is characterized by prominent manifestations of membranous hyperplasia, which are easy to misdiagnose. The clinical symptoms are severe. Massive proteinuria and hypoproteinemia are conspicuous, and most patients are accompanied by renal insufficiency and microscopic hematuria. CASE SUMMARY: A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior, and renal biopsy in the hospital suggested moderate-to-severe mesangial proliferating glomerulonephritis (MsPGN). She had taken a glucocorticoid, cyclophosphamide, mycophenolate mofetil, and other treatments and achieved brief partial remission. Recently, the patient visited our hospital due to massive proteinuria. Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli. A bone marrow examination was performed to exclude hematologic malignancy, and a diagnosis of PGNMID was established. The patient showed remission after four cycles of a bortezomib + cyclophosphamide + dexamethasone scheme. CONCLUSION: PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis. Although it often occurs in middle-aged and elderly individuals, it cannot be readily excluded in young people, even when serum immunofixation electrophoresis is negative. IgG subtype and light chain staining are necessary when this disease is highly suspected. An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies. Their overlap constitutes a rare rheumatologic disease. To date, only dozens of such cases with biopsy-proven glomerulonephritis have been reported worldwide typically in women of childbearing age. Here, we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life. CASE SUMMARY: A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years. As his symptoms were not completely relieved, he visited our hospital for further treatment. Laboratory examinations revealed kidney dysfunction, severe anaemia, hypocom-plementemia, glomerular proteinuria, and microscopic haematuria. Antinuclear antibodies, as well as anti-dsDNA antibodies, were positive. Computed tomography of the chest showed right pleural effusion. Renal biopsy was performed, and histology suggested crescentic glomerulonephritis, pauci-immune type. After treatment with plasmapheresis, glucocorticoid, and cyclo-phosphamide, the disease was in remission, and the patient remained in a stable condition for over 3 years post-hospital discharge. CONCLUSION: Due to its complexity and rarity, SLE and AAV overlap syndrome is easily misdiagnosed. An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.

Evaluation of blood pressure lowering effect by generic and brand-name antihypertensive drugs treatment: a multicenter prospective study in China.

BACKGROUND: Generic drugs are bioequivalent to their brand-name counterparts; however, concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies. The purpose of this study was to evaluate the long-term antihypertensive efficacy, cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs. METHODS: In a multicenter, community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years, we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2, 2176 patients using brand-name drugs and 4352 patients using generic drugs. RESULTS: There were no significant differences between generic drugs and brand-name drugs in blood pressure (BP)-lowering efficacy, BP control rate, and cardiovascular outcomes including coronary heart disease and stroke. The adjusted mean (95% confidence interval [CI]) of systolic BP (SBP)-lowering was -7.9 mmHg (95% CI, -9.9 to -5.9) in the brand-name drug group and -7.1 mmHg (95% CI, -9.1 to -5.1) in the generic drug group after adjusting for age, sex, body mass index, number of antihypertensive drugs and traditionally cardiovascular risk factors. Among patients aged <60 years, brand-name drugs had a higher BP control rate (47% vs. 41%; P = 0.02) and a greater effect in lowering SBP compared with generic drugs, with the between-group difference of 1.5 mmHg (95% CI, 0.2-2.8; P = 0.03). BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs (46% vs. 40%; P = 0.01). Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of $315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment. CONCLUSIONS: Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits, especially in low- and middle-income areas.

Facile and Site-Selective Synthesis of an Amine-Functionalized Covalent Organic Framework.

Amine-functionalized covalent organic frameworks (COFs) hold great potential in diversified applications. However, the synthesis is dominated by postsynthetic modification, while the de novo synthesis allowing for direct installation of amine groups remains a formidable challenge. Herein, we develop a site-selective synthetic strategy for the facile preparation of amine-functionalized hydrazone-linked COF for the first time. A new monomer 2-aminoterephthalohydrazide (NH2-Th) bearing both amine and hydrazide functionalities is designed to react with benzene-1,3,5-tricarbaldehyde (Bta). Remarkably, the different activity of amine and hydrazide groups toward aldehyde underpin the highly site-selective synthesis of an unprecedented NH2-Th-Bta COF with abundant free amine groups anchored in the well-defined pore channels. Interestingly, NH2-Th-Bta COF exhibits dramatically enhanced iodine uptake capacity (3.58 g g-1) in comparison to that of the nonfunctionalized Th-Bta COF counterpart (0.68 g g-1), and many reported porous adsorbents, despite its low specific surface area. Moreover, NH2-Th-Bta COF possesses exceptional cycling capability and retained high iodine uptake, even after six cycles. This work not only provides a simple and straightforward route for the de novo synthesis of amine-functionalized COFs but also uncovers the great potential of amine-functionalized COFs as adsorbents in the efficient removal of radioiodine and beyond.

Goodpasture syndrome and hemorrhage after renal biopsy: A case report.

BACKGROUND: Goodpasture syndrome (GS) is a rare disease, the morbidity of which is estimated to be 0.5-0.8 per million per year. Hemorrhage is the most serious complication in renal biopsy. Despite the fact that both GS and hemorrhage after renal biopsy are rare, it has not been reported that they are likely to occur in the same patient. CASE SUMMARY: A 30-year-old man with diffuse pulmonary hemorrhage and rapid progressive renal function caused by anti-glomerular basement membrane disease presented atypical symptoms without hemoptysis, accompanied by life-threatening hypoxemia. Plasmapheresis was performed, and glucocorticoids and cyclophosphamide were administered. The patient started to show signs of improvement. Percutaneous renal biopsy is an appropriate diagnostic measure that is commonly safe, but this patient experienced hemorrhage after operation, thus necessitating embolization of the renal artery to stop the bleeding. The patient's condition was improved, and the serum anti-glomerular basement membrane antibody level was 106 AU/mL (normal range: < 24 AU/mL) and slowly decreased. His discharge medications were oral daily prednisone (30 mg) and continued maintenance hemodialysis. CONCLUSION: GS is a rare organ-specific autoimmune disease that is invariably ubiquitous in the lung and kidney areas. Renal biopsy is the appropriate procedure for the treatment of GS disease, although it is an invasive measure.

[Seedlings regenerative dynamics of dominant trees in a secondary forest in montane region of eastern Liaoning Province, China]. / è¾½ä¸œå±±åŒºæ¬¡ç”Ÿæž—ä¹”æœ¨ä¼˜åŠ¿æ ‘ç§å¹¼è‹—æ›´æ–°åŠ¨æ€.

To reveal the seedlings dynamics of dominant trees and their response to canopy changes (as indicated by changes in leaf area index), we analyzed the seedlings dynamics of dominant trees and canopy structure during forest regeneration based on three-year (2014 to 2016) censuses and hemispherical photography in a 4 hm2 forest dynamics monitoring plot. The results showed that canopy LAI first decreased and then increased during the survey period, with significant interannual difference. The seedlings of 12 dominant tree species showed notable response to the change of canopy structure, with the response varying among different tree species. The relative abundance or frequency of seedlings for neutral tree species generally increased with the decreases of canopy LAI. The relative abundance or frequency of seedlings of light-demanding tree species generally decreased with the increases of canopy LAI. In multi-response permutation procedures by analyzing the numeric composition and distribution of dominant tree seedlings, there was significant difference among the three censuses. Such interannual difference gradually decreased from 2014 to 2016. Significant change occurred in the indicator species of dominant tree seedlings, reflecting their responses to the changes of canopy structure.