Waste rubber - Black pollution reframed as a global issue: Ecological challenges and sustainability initiatives.

In contrast to "white pollution" originating from waste plastics, waste rubber is often referred to as "black pollution." The quantity and variety of waste rubber are increasing at an alarming rate, with a considerable fraction entering the global ecosystem via various pathways. This study presents the first critical review of waste rubber research with a focus on the risks associated with toxicant discharge and existing problems in waste rubber disposal, management, and recycling practices. We aim to obtain a comprehensive understanding of current research, particularly regarding the ecological impacts of these wastes, highlight major gaps, and propose the most significant research directions. A total of 192 studies published in journals were critically analysed. The importance of conducting long-term and large-scale experiments and developing efficient waste rubber recycling systems is also emphasised. This study highlights the need to address the challenges posed by waste rubber pollution and offers insights and references for undertaking ecological risk assessments and understanding the mechanisms underlying toxicant behaviour. Suggestions and countermeasures are proposed with ecosystem sustainability as the ultimate goal. Further long-term, comprehensive, and systematic research in this area is required.

Recent advances in biological therapy of diabetic retinopathy / 眼科新进展

Diabetic retinopathy(DR)is one of the most common fundus vascular diseases and a leading cause of blindness in adults of working age.The occurrence and development of DR involves a variety of pathophysiologic mecha-nisms,including metabolic dysregulation,oxidative stress,inflammation,and neurovascular unit hypofunction.Conven-tional clinical treatments,such as anti-vascular endothelial growth factor drugs and retinal laser photocoagulation,have long treatment cycles and variable outcomes in some patients and sometimes require vitrectomy in the later stages of the disease.With the in-depth research on the molecular level of the pathogenesis of DR,a number of biological therapeutic modalities,such as targeted therapy,gene therapy,immunotherapy and cell therapy,have received more and more atten-tion from researchers.This review summarizes the biologic therapeutic modalities currently available for DR and outlines the benefits and limitations of these approaches with a view to informing researchers.

Competitive interactions and coexistence of sympatric flagship carnivores in Asia.

Understanding the competition and coexistence of flagship carnivores is key to creating strategies for their conservation in the face of global carnivore declines. Although studies exploring the dynamics and competition between tigers (Panthera tigris) and leopards (P. pardus) span decades, there is a lack of understanding regarding the factors that influence their coexistence mechanisms on a broad scale, as well as the drivers determining their exploitative and interference competition. We gathered a comprehensive list of research papers among which 36 papers explored the interspecific interactions between tigers and leopards and tested the influence of biotic and abiotic factors on the coexistence mechanisms along three dimensions using multiple response variables regression models; we also tested the influence of ecological drivers determining the exploitative or interference competition between tigers and leopards. Elevation and ungulate density were the most important predictors in regulating the coexistence mechanisms. Tigers and leopards exhibited more positive relations/higher overlaps as elevation increased in the spatial niche. In addition, they showed a higher dietary overlap in the prey-rich regions. We determined that interference competition between tigers and leopards was less frequently observed in habitats with dense tree cover and homogeneous vegetation structures. Meanwhile, studies with multiple metrics would promote the detection of interference competition. Our study provides new insight into the competitive interactions and coexistence mechanisms of tigers and leopards on a broad scale. Policy-makers and managers should pay more attention to the factors of elevation, prey abundance, and habitat structures for the conservation of tigers and leopards.

Impact of miR-30e-5p on the invasion and migration of hepatocellular carcinoma cells through targeting PIK3CD-mediated PI3K/AKT/mTOR signaling pathway / 中国现代普通外科进展

Objective:To explore the mechanism of miR-30e-5p inhibiting the invasion and migration of hepatoma cells by targeting phosphoinositide-3-kinase catalytic delta polypeptide(PIK3CD)-mediated phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of the rapamycin(mTOR)signaling pathway.Methods:HepG2 cells were divided into control group,miR-30e-5p mimics group,PIK3CD knockdown group,negative control group,and miR-30e-5p mimics+PIK3CD overexpression group by transfecting the corresponding plasmids,the expression of miR-30e-5p,PIK3CD and PI3K/AKT/mTOR signaling pathway was detected by qRT-PCR and Western blot;the proliferation rate of Hep G2 cells in each group was detected by CCK-8 method;cell migration and invasion were measured by cell scratch test and Transwell test;the expression of matrix metalloproteinase(MMP)2,MMP9,E-cadherin,N-cadherin,Vimentin in Hep G2 cells of each group were detected by Western blot.The targeting regulation of miR-30e-5p on PIK3CD in Hep G2 cells was detected by double luciferase report assay.Results:Compared with the control group,the proliferation rate,migration rate,invasion number,the expression of N-cadherin,MMP2 and MMP9 proteins,the expression of PIK3CD protein and mRNA,p-P13K/PI3K,p-AKT/AKT,and p-mTOR/mTOR in the miR-30e-5p mimics group and PIK3CD knockdown group were lower(P＜0.05),the expression of E-cadherin protein was higher(P＜0.05).Overexpression of PIK3CD attenuates the inhibitory effects of miR-30e-5p mimics on proliferation,migration and invasion of hepatocellular carcinoma cells and elevates the expression of PI3K/AKT/mTOR pathway-related proteins;miR-30e-5p targets down-regulation of PIK3CD expression.Conclusion:Up-regulation of miR-30e-5p can prevent PI3K/AKT/mTOR signal activation by decreasing the expression of PIK3CD,thereby inhibiting the proliferation,migration and invasion of hepatocellular carcinoma cells.

Assessing mammal population densities in response to urbanization using camera trap distance sampling.

Environmental filtering is deemed to play a predominant role in regulating the abundance and distribution of animals during the urbanization process. However, the current knowledge about the effects of urbanization on the population densities of terrestrial mammals is limited. In this study, we compared two invasive mammals (dogs Canis lupus familiaris and cats Felis silvestris) and three indigenous mammals (Siberian weasels Mustela sibirica, Amur hedgehogs Erinaceus amurensis, and Tolai hares Lepus tolai) in response to urbanization using camera trap distance sampling (CTDS) in the rural-urban landscape of Tianjin, China. We used generalized additive mixed models (GAMMs) to test the specific responses of their densities to levels of urbanization. Invasive dogs (2.63 individuals/km2, 95% CI: 0.91-7.62) exhibited similar density estimations to cats (2.15 individuals/km2, 95% CI: 1.31-3.50). Amur hedgehogs were the most abundant species (6.73 individuals/km2, 95% CI: 3.15-14.38), followed by Tolai hares (2.22 individuals/km2, 95% CI: 0.87-5.68) and Siberian weasels (2.15 individuals/km2, 95% CI: 1.06-4.36). The densities of cats, Siberian weasels, and Amur hedgehogs increased with the level of urbanization. The population densities of dogs and cats were only influenced by urban-related variables, while the densities of Siberian weasels and Amur hedgehogs were influenced by both urban-related variables and nature-related variables. Our findings highlight that the CTDS is a suitable and promising method for wildlife surveys in rural-urban landscapes, and urban wildlife management needs to consider the integrated repercussions of urban- and nature-related factors, especially the critical impacts of green space habitats at finer scales.

Exploration and consideration on establishing a core outcome set of Traditional Chinese Medicine clinical trials in distal radius fracture / 中国骨伤

There are inconsistencies in treatment outcomes, measurement instruments, and criteria for assessing clinical effectiveness in studies related to distal radius fractures (DRF), resulting in potential biases and failing to provide high-quality clinical evidence. To address these challenges, international researchers have reached a consensus on developing the core outcome indicator set for distal radius fractures(COS-DRF). However, it's important to note that the existing COS-DRF framework could not reflect the unique characteristics of Traditional Chinese Medicine (TCM) treatment. Currently, there are no established standards for treatment outcomes and measurement instruments specific to TCM clinical research, nor has a COS-DRF been established for TCM clinical studies in China. In light of these gaps, our research team aims to construct a core set of treatment outcomes for TCM clinical research on distal radius fractures. This involves compiling a comprehensive list of treatment outcomes and measurement instruments, initially derived from a thorough literature review and expert consensus, which will then undergo further refinement and updates based on real-world clinical experiences, incorporating feedback from 2 to 3 rounds of expert consensus or Delphi questionnaire surveys. Our goal is to establish a COS-DRF or CMS-DRF that aligns with the principles and practices of TCM, and provide high-quality evidence for clinical practice.

Establishment and evaluation of a quantitative TaqMan RT-PCR for the detection of SARS-CoV-2 Omicron variants / 中华微生物学和免疫学杂志

Objective:To develop a rapid, simple and cost-effective quantitative TaqMan RT-PCR (RT-qPCR) that could be used as an alternative to sequencing for the detection of Omicron variants and to evaluate its performance.Methods:Primers and TaqMan probes targeting the conserved domains of SARS-CoV-2 ORF1ab and the high-frequency mutation sites in the S gene of Omicron variants were designed. Then a RT-qPCR for the detection of Omicron variants was established. The consistency of the method was verified using samples identified by whole-genome sequencing. The specificity and sensitivity of the method were also evaluated.Results:The established RT-qPCR could distinguish Omicron variants from early epidemic A strains and Alpha and Delta variants of SARS-CoV-2, and the results were consistent with those of whole-genome sequencing with a coincidence rate of 100% (28/28). There was no cross-reactivity with other six respiratory viruses or coxsackievirus group A16. For RNA standards, this method showed good linearity in the range of 10 9-10 3 copies/μl with a correlation coefficient ( R2) greater than 0.99 and detection sensitivity of 10 3 copies/μl. Conclusions:The RT-qPCR designed in this study for Omicron variant detection had good sensitivity and specificity and could be easily performed in laboratories, which would greatly facilitate the monitoring of Omicron variants.

Global development trend of ECMO based on utility patent analysis / 医疗卫生装备

The global patent data on extracorporeal membrane oxygenation(ECMO)in IncomPat Global Patent Database as of August 29,2022 were retrieved.The development trend and layout of ECMO industry were analyzed in terms of global patent application trend,patent distribution,patent technology,major patent applicants and their patent layout.Some suggestions were put forward for the innovation and development of ECMO industry in China so as to provide references for the formulation of national industrial policy,planning of industry technology direction and enterprise technology research and development and patent layout.[Chinese Medical Equipment Journal,2023,44(10):68-75]

Syphilis-related membranous proliferative glomerulonephritis with fever, skin rash and generalized lymph node enlargement as the initial manifestations: a case report / 中华肾脏病杂志

A case of syphilis-related membranous proliferative glomerulonephritis is reported, presenting with fever, rash, generalized lymphadenopathy, and peripheral hypocytosis as the initial symptoms. The patient was admitted to the hospital and underwent various examinations to rule out lymphoma and other diseases. Subsequently, the patient developed edema with proteinuria. The toluidine red unheated serum test (TRUST) was 1∶4 (+) and the treponema pallidum particle agglutination (TPPA) test was >1∶160 (+). The pathological results of renal biopsy revealed membranous proliferative glomerulonephritis. The diagnosis of the patient was considered syphilitic nephropathy. Treatment with penicillin resulted in improvement of the condition. The coexistence of syphilitic nephropathy and membranous proliferative glomerulonephritis is rare and should be given careful attention in clinical practice. Antisyphilitic treatment improves the prognosis.

Effect of home-based early intensive behavioral intervention using VB-MAPP on verbal ability in children with autism spectrum disorder / 四川精神卫生

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］

Research progress in pelvic floor ultrasound for assessing the morphology and function of levator ani muscle in women / 中南大学学报(医学版)

Pelvic floor ultrasound can clearly visualize the position and morphology of pelvic floor organs, observe the pelvic organ prolapse in real-time, and quantify and analyze the degree of the levator ani muscle injury, which is the most common imaging method to assess the morphology and function of the levator ani muscle to date. The different ultrasound imaging techniques provide a variety of indicators, each with its own advantages and limitations.Furthermore, two-dimensional ultrasound is the basis of imaging, but it fails to detect cross-sectional images of the pelvic floor; three-dimensional ultrasound can acquire the axial plane of the levator hiatus; tomographic ultrasound imaging allows real-time observation of the levator ani muscle injury; shear wave elastography can provide a quantitative assessment of the contractility and elastic characteristics of the levator ani muscle in real-time. It is of great significance to summarize the basic principles of various ultrasound imaging techniques, summarize the ultrasound image characteristics of levator ani muscle and its hiatus in different populations and different states, and explore the cut-off values and diagnostic criteria-related ultrasound parameters for improving the diagnostic efficiency of pelvic floor ultrasound for levator ani muscle injury, leading to reducing missed diagnosis and misdiagnosis of lesions.

Multi-omics provide mechanistic insight into the Pb-induced changes in tadpole fitness-related traits and environmental water quality.

Water pollution from lead/Pb2+ poses a significant threat to aquatic ecosystems, and its repercussions on aquatic animals have received considerable attention. Although Pb2+ has been found to affect numerous aspects of animals, including individual fitness, metabolic status, and symbiotic microbiota, few studies have focused on the associations between Pb2+-induced variations in fitness, metabolome, symbiotic microbiome, and environmental parameters in the same system, limiting a comprehensive understanding of ecotoxicological mechanisms from a holistic perspective. Moreover, most ecotoxicological studies neglected the potential contributions of anions to the consequences generated by inorganic lead compounds. We investigated the effects of Pb(NO3)2 at environmentally relevant concentrations on the Rana omeimontis tadpoles and the water quality around them, using blank and NaNO3-treated groups as control. Results showed that Pb(NO3)2 not only induced a rise in water nitrite level, but exposure to this chemical also impaired tadpole fitness-related traits (e.g., growth and development). The impacts on tadpoles were most likely a combination of Pb2+ and NO3-. Tissue metabolomics revealed that Pb(NO3)2 exposure influenced animal substrate (i.e., carbohydrate, lipid, and amino acid) and prostaglandin metabolism. Pb(NO3)2 produced profound shifts in gut microbiota, with increased Proteobacteria impairing Firmicutes, resulting in higher aerobic and possibly pathogenic bacteria. NaNO3 also influenced tadpole metabolome and gut microbiome, in a manner different to that of Pb(NO3)2. The presence of NO3- seemed to counteract some changes caused by Pb2+, particularly on the microbiota. Piecewise structural equation model and correlation analyses demonstrated connections between tissue metabolome and gut microbiome, and the variations in tadpole phenotypic traits and water quality were linked to changes in tissue metabolome and gut microbiome. These findings emphasized the important roles of gut microbiome in mediating the effects of toxin on aquatic ecosystem. Moreover, it is suggested to consider the influences of anions in the risk assessment of heavy metal pollutions.

Effect and mechanism of fibroblast growth factor on proliferation and transdifferentiation of cardiac fibroblasts in rats / 解剖学报

Objective To investigate the effect of fibroblast growth factor (FGF) on the proliferation and transdifferentiation of cardiac fibroblasts ( CFs ) into myofibroblasts ( MFs ). Methods Rat CFs were isolated and cultured, and then induced by FGF. CCK-8 was used to detect the cell activity and proliferation. Immunofluorescence and Western blotting were used to detect the expression of a smooth muscle actin ( α-SMA ) and collagen I ( Col I ). Results The expression and activation of α-SMA and Col I increased with the increase of CFs culture generation. The number of CFs induced by FGF did not increased significantly; the expression of α-SMA in CFs induced by FGF1 and FGF2 decreased, and the number of activated MFs decreased. Conclusion FGF family has no effect on the proliferation of CFs, but FGF1 and FGF2 can inhibit the activation of CFs and reduce the differentiation into MFs.

E. coli diversity: low in colorectal cancer.

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

Acupuncture therapy with point selection based on syndrome differentiation along the meridians for functional dyspepsia: a randomized controlled trial / 针灸推拿医学（英文版）

Objective: To observe the difference in clinical efficacy between acupuncture with point selection based on syndrome differentiation along the meridians and acupuncture at non-meridian and non-acupoint points for functional dyspepsia (FD). Methods: A total of 74 FD patients were randomized into an observation group and a control group, with 37 cases in each group. Both groups received acupuncture treatment. Zusanli (ST 36) and Neiguan (PC 6) were selected in the observation group, with Taichong (LR 3) and Neiting (ST 44) added for excess syndrome, and Gongsun (SP 4) and Yinlingquan (SP 9) added for deficiency syndrome. Four non-meridian and non-acupoint points were selected in the control group. The treatments in both groups were performed once a day with a 2-day break after 5 consecutive treatments, which constituted one treatment course. A total of 4 courses were performed. The scores of Nepean dyspepsia index (NDI) and Leeds dyspepsia questionnaire (LDQ) were recorded before and after treatment, and during follow-up (8, 12, 16, 20 and 24 weeks after recruitment) to assess the clinical efficacy. Results: The NDI scores in the two groups after treatment and at each time point during follow-up were higher than those before treatment (all P<0.05), and the LDQ scores were lower than those before treatment (all P<0.05). The NDI scores after treatment and at each time point during follow-up in the observation group were higher than those in the control group (all P<0.01); the total LDQ score and scores of upper abdominal pain, postprandial satiety and upper abdominal burning sensation after treatment and at each time point during follow-up in the observation group were significantly lower than those in the control group (P<0.01 or P<0.05).. Conclusion: Acupuncture with point selection based on syndrome differentiation along the meridians has a better curative effect than acupuncture at non meridian and non-acupoint points in the treatment of FD.

Efficient Human Cytomegalovirus Replication in Primary Endothelial Cells Is SOCS3 Dependent.

BACKGROUND: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. We hypothesized that HCMV exploits SOCS1 and/or SOCS3 to its advantage. METHODS: All experiments were carried out with primary human lung-derived microvascular endothelial cells (HMVEC). SOCS1 and SOCS3 were silenced by transfecting the cells with siRNA. HCMV was propagated and titered on human lung-derived fibroblasts MRC5. Real-time PCR and Western blot were used to detect mRNA and protein levels, respectively. RESULTS: The data presented show that an efficient replication of HCMV in HMVEC is dependent on SOCS3 protein. Time course analysis revealed an increase in SOCS3 protein levels in infected cells. Silencing of SOCS3 (siSOCS3) resulted in inhibition of viral immediate early, early, and late antigen production. Consistently, HCMV titers produced by siSOCS3 cultures were significantly decreased when compared to control transfected cultures (siCNTRs). STAT1 and STAT2 phosphorylation was increased in siSOCS3-infected cells when compared to siCNTR-treated cells. CONCLUSION: These findings indicate the implication of SOCS3 in the mechanism of HCMV-mediated control of cellular immune responses.

Comparative analysis of clinico-pathological characteristics and outcomes in malignant hypertension patients with and without primary glomerular diseases / 中华肾脏病杂志

Objective@#To investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases.@*Methods@#Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases.@*Results@#Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5±6.5) years old and (34.7±8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03±2.71) g vs (1.45±0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P<0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P<0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95% CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6% vs 53.3%, Log-rank χ2=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95% CI 1.372-25.112, P=0.017).@*Conclusions@#Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.

Pharmacokinetics and absolute bioavailability of isoschaftoside in rat by LC-MS/MS / 中国药科大学学报

@#The aim of this study was to develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties and absolute bioavailability of isoschaftoside in rats. Blood sampling was performed at different time points after intragastric administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg)and 0. 5 mg/kg by intravenous injection. Isoschaftoside was analyzed by a validated LC-MS/MS method in plasma; the pharmacokinetic parameters and absolute bioavailability were evaluated by software DAS 3. 0. The results showed that the linear concentration ranges of isoschaftoside was 1. 0- 500. 0 ng/mL(r=0. 997 6). The precision, accuracy, matrix effect, sensitivity, dilution reliability and stability met the requirements of biological sample analysis. For ig administration of isoschaftoside(1. 5, 3. 0, 6. 0 mg/kg), the pharmacokinetic parameter cmax was(109. 34±22. 87), (259. 84±95. 35)and(499. 26±288. 09)ng/mL; AUC0-t was(310. 57±46. 18), (552. 67±207. 14)and(1 075. 03±371. 19)h ·ng/mL; t1/2 was(2. 36±0. 22), (2. 91±0. 19)and(3. 04±0. 86)h; tmax was(1. 03±0. 25), (1. 18±0. 17)and(1. 5±0. 43)h; MRT0-t was(11. 33±1. 53), (11. 27±1. 09)and(8. 29±0. 76)h, respectively. For iv administration of isoschaftoside(0. 5 mg/kg), the pharmacokinetic parameter AUC0-t was(1 536±421. 3)h ·ng/mL; t1/2 was(2. 57±0. 46)h; MRT0-t was(9. 55±2. 37)h. Furthermore, the absolute bioavailability was 6. 73%, 5. 99%, 5. 80%, respectively. The LC-MS/MS analysis method established in this study was accurate and sensitive, so it can be applied to the pharmacokinetic study of isoschaftoside.

Comparative analysis of clinico - pathological characteristics and outcomes in malignant hypertension patients with and without primary glomerular diseases / 中华肾脏病杂志

Objective To investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases. Methods Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases. Results Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5 ± 6.5) years old and (34.7 ± 8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03 ± 2.71) g vs (1.45 ± 0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P<0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P<0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95％CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6％ vs 53.3％, Log-rank χ2=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95％CI 1.372-25.112, P=0.017). Conclusions Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.

Progress of inhibiting epithelial-mesenchymal transition in retinal pigment epithelial cells / 国际眼科杂志(Guoji Yanke Zazhi)

@#Epithelial-mesenchymal transition(EMT)of retinal pigment epithelial cells(RPE)plays a key role in proliferative vitreoretinopathy(PVR), and also decreases the therapeutic effect of anti-vascular endothelial growth factor(anti-VEGF)to choroidal neovascularization(CNV). In addition, cells transplantation has been becoming a potential therapeutic method to treat age-related macular degeneration(AMD), and some cells sources like human embryonic stem cells(hESC)or induced pluripotent stem cell(iPSC)induced RPE cells, and fetal RPE cells have been attempted. However, EMT, as a common problem, decreases cells proliferation and differentiation efficiency, and it will reduce therapeutic effect and the number of therapeutic populations. So, in this article, we reviewed some possible methods to inhibit EMT.