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The objective of this study is to investigate the effects of various doses of esketamine on the median effective concentration (EC 50 ) of propofol required for inhibiting body movement during hysteroscopy. Additionally, this research aims to explore the pharmacodynamic interactions between esketamine and propofol. Prospective, double-blind, up-down sequential allocation study. Operating room, post-anesthesia care unit (PACU), and general ward. A total of 90 patients were allocated into three groups in a randomized, double-blinded manner as follows: 0.1 mg/kg esketamine combined with propofol intravenous injection (EP 0.1 ) group, 0.2 mg/kg esketamine combined with propofol intravenous injection (EP 0.2 ) group, 0.3 mg/kg esketamine combined with propofol of intravenous injection (EP 0.3 ) group. For the initial patient in each group, the starting effector target concentration of propofol was set at 4 µg/ml. Each patient received an initial intravenous injection of 0.04 mg/kg midazolam, followed by the administration of the appropriate dose of esketamine. Ten seconds after the esketamine injection, propofol was administered intravenously to achieve the target concentration. In accordance with the sequential method principle, the concentration of propofol for the subsequent patient was adjusted based on the response of the previous patient. Effective inhibition of body movement was defined as the absence of any involuntary body movements throughout the entire surgical process. If the previous patient exhibited body movements, the propofol concentration for the next patient was increased by 0.5 µg/ml; conversely, if no movements were observed, it was decreased by 0.5 µg/ml. The up-down sequential allocation method and probit regression were used to calculate the EC 50 of propofol. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and Depression (HADS-D) score, adverse events, hemodynamic changes, demographic data and clinical characteristics. The EC 50 of propofol was 3.849 μg/ml (95% CI: 3.419-4.281) in the EP 0.1 group, 3.641 μg/ml (95% CI: 2.807-4.200) in the EP 0.2 group, and 3.417 μg/ml (95% CI: 2.845-3.852) in the EP 0.3 group. These findings suggest that esketamine can dose-dependently reduce the EC 50 of propofol. Esketamine can dose-dependently reduce the EC 50 of propofol in hysteroscopy, while concurrently lowering patients' HADS-A and HADS-D scores 24 h post-operation. It is concluded that the optimal dose of esketamine, when combined with propofol for hysteroscopy, is 0.3 mg/kg., (© 2024. The Author(s).)

This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Staphylococcus aureus. A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Study Objective: Recent studies have shown that dexmedetomidine can be safely used in peripheral nerve blocks and spinal anesthesia. Epidural administration of dexmedetomidine produces analgesia and sedation, prolongs motor and sensory block time, extends postoperative analgesia, and reduces the need for rescue analgesia. This investigation seeks to identify the median effective concentration (EC 50 ) of ropivacaine for epidural motor blockade, and assess how incorporating varying doses of dexmedetomidine impacts this EC 50 value., Design: Prospective, double-blind, up-down sequential allocation study., Setting: Operating room, post-anesthesia care unit, and general ward., Interventions: One hundred and fifty patients were allocated into five groups in a randomized, double-blinded manner as follows: NR (normal saline combined with ropivacaine) group, RD 0.25 (0.25 μg/kg dexmedetomidine combined with ropivacaine) group, RD 0.5 (0.5 μg/kg dexmedetomidine combined with ropivacaine) group, RD 0.75 (0.75 μg/kg dexmedetomidine combined with ropivacaine) group, RD 1.0 (1.0 μg/kg dexmedetomidine combined with ropivacaine) group. The concentration of epidural ropivacaine for the first patient in each group was 0.5%. Following administration, the patients were immediately placed in a supine position for observation, and the lower limb motor block was assessed every 5 min using the modified Bromage score within 30 min after drug administration. According to the sequential method, the concentration of ropivacaine in the next patient was adjusted according to the reaction of the previous patient: effective motor block was defined as the modified Bromage score > 0 within 30 min after epidural administration. If the modified Bromage score of the previous patient was >0 within 30 min after drug administration, the concentration of ropivacaine in the next patient was decreased by 1 gradient. Conversely, if the score did not exceed 0, the concentration of ropivacaine in the next patient was increased by 1 gradient. The up-down sequential allocation method and probit regression were used to calculate the EC 50 of epidural ropivacaine., Measurements: Adverse events, hemodynamic changes, demographic data and clinical characteristics., Main Results: The EC 50 of epidural ropivacaine required to achieve motor block was 0.677% (95% CI , 0.622-0.743%) in the NR group, 0.624% (95% CI , 0.550-0.728%) in the RD 0.25 group, 0.549% (95% CI , 0.456-0.660%) in the RD 0.5 group, 0.463% (95% CI , 0.408-0.527%) in the RD 0.75 group, and 0.435% (95% CI , 0.390-0.447%) in the RD 1.0 group. The EC 50 of the NR group and the RD 0.25 group were significantly higher than that of the RD 0.75 and the RD 1.0 groups, and the EC 50 of the RD 0.5 group was significantly higher than that of the RD 1.0 group., Conclusion: The EC 50 of epidural ropivacaine required to achieve motor block was 0.677% in the NR group, 0.624% in the RD 0.25 group, 0.549% in the RD 0.5 group, 0.463% in the RD 0.75 group, and 0.435% in the RD 1.0 group. Dexmedetomidine as an adjuvant for ropivacaine dose-dependently reduce the EC 50 of epidural ropivacaine for motor block and shorten the onset time of epidural ropivacaine block. The optimal dose of dexmedetomidine combined with ropivacaine for epidural anesthesia was 0.5 μg/kg., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wan, Lin, Wu, Feng, Wang and Wang.)

Background: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC., Methods: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation., Results: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727., Conclusions: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models., (© 2024. Society of Surgical Oncology.)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

We have utilized reversible covalent bonding to expand the accessible states of a molecular switch. Introducing a hydroxyl group onto the donor moiety of a donor-acceptor Stenhouse adduct (DASA) imparts an acidity response by forming an oxazolidine ring through intramolecular nucleophilic addition. Furthermore, we observed distinct color changes under cryogenic conditions, extending the thermal responsiveness beyond the cyclization equilibrium observed at elevated temperatures. These unique responses present promising prospects for diverse applications compared to traditional photoinduced binary isomerization.

Background: Patients often experience shivering after spinal anesthesia. In recent years, more and more studies have compared the efficacy and side effects of intravenous butorphanol and tramadol in the treatment of shivering after spinal anesthesia. Therefore, we conducted a MATE analysis and systematic review to compare the efficacy and side effects of butorphanol vs. tramadol in the treatment of shivering after spinal anesthesia., Methods: PubMed, Cochrane Library, and Embase databases were searched for randomized controlled trials (RCTs) from inception to 30 December 2022, comparing the effects of butorphanol vs. tramadol for the control of shivering after spinal anesthesia. Data assessment and collection were analyzed using the Review Manager 5.4 software., Results: Five randomized controlled trials involving 302 adult patients were included in this meta-analysis. The results showed that butorphanol has a shorter time to cease shivering (standardized mean difference (SMD) = -0.53; 95% confidence interval (CI) [-0.89, -0.17], P = 0.004, I 2 = 0%), a higher rate of cessation of shivering within 1 min after administering the study drugs (relative risk (RR), 1.69; 95% CI [1.15,2.48], P = 0.008, I 2 = 0%), and higher incidences of sedation (RR, 2.98; 95% CI [2.11, 4.21], P <0.00001, I 2 = 0%), compared with tramadol., Conclusion: In the treatment of shivering after spinal anesthesia, butorphanol has a shorter onset time and a higher rate of cessation of shivering within 1 min after the study drugs were administered than tramadol. Therefore, butorphanol is superior to tramadol in the treatment of shivering after spinal anesthesia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wan, Li, Zeng, Li and Wang.)

Background: This study aimed to comprehensively evaluate the accuracy and effect of computed tomography (CT) and magnetic resonance imaging (MRI) based on artificial intelligence (AI) algorithms for predicting lymph node metastasis in breast cancer patients., Methods: We systematically searched the PubMed, Embase and Cochrane Library databases for literature from inception to June 2023 using keywords that included 'artificial intelligence', 'CT,' 'MRI', 'breast cancer' and 'lymph nodes'. Studies that met the inclusion criteria were screened and their data were extracted for analysis. The main outcome measures included sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC)., Results: A total of 16 studies were included in the final meta-analysis, covering 4,764 breast cancer patients. Among them, 11 studies used the manual algorithm MRI to calculate breast cancer risk, which had a sensitivity of 0.85 (95% confidence interval [CI] 0.79-0.90; p < 0.001; I 2  = 75.3%), specificity of 0.81 (95% CI 0.66-0.83; p < 0.001; I 2  = 0%), a positive likelihood ratio of 4.6 (95% CI 4.0-4.8), a negative likelihood ratio of 0.18 (95% CI 0.13-0.26) and a diagnostic odds ratio of 25 (95% CI 17-38). Five studies used manual algorithm CT to calculate breast cancer risk, which had a sensitivity of 0.88 (95% CI 0.79-0.94; p < 0.001; I 2  = 87.0%), specificity of 0.80 (95% CI 0.69-0.88; p < 0.001; I 2  = 91.8%), a positive likelihood ratio of 4.4 (95% CI 2.7-7.0), a negative likelihood ratio of 0.15 (95% CI 0.08-0.27) and a diagnostic odds ratio of 30 (95% CI 12-72). For MRI and CT, the AUC after study pooling was 0.85 (95% CI 0.82-0.88) and 0.91 (95% CI 0.88-0.93), respectively., Conclusion: Computed tomography and MRI images based on an AI algorithm have good diagnostic accuracy in predicting lymph node metastasis in breast cancer patients and have the potential for clinical application., (© 2023. The Author(s).)

Significance Statement: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility., Background: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated., Methods: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression., Results: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03)., Conclusions: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility., (Copyright © 2023 by the American Society of Nephrology.)

Smad ubiquitylation regulatory factor 1 (Smurf1) is an important homologous member of E6-AP C-terminus type E3 ubiquitin ligase. Initially, Smurf1 was reportedly involved in the negative regulation of the bone morphogenesis protein (BMP) pathway. After further research, several studies have confirmed that Smurf1 is widely involved in various biological processes, such as bone homeostasis regulation, cell migration, apoptosis, and planar cell polarity. At the same time, recent studies have provided a deeper understanding of the regulatory mechanisms of Smurf1's expression, activity, and substrate selectivity. In our review, a brief summary of recent important biological functions and regulatory mechanisms of E3 ubiquitin ligase Smurf1 is proposed., (© 2023. Huazhong University of Science and Technology.)

Introduction: Previous studies suggested that sevelamer carbonate is well tolerated with a favorable efficacy and safety profile in both dialysis and nondialysis patients in Europe; however, the efficacy remains controversial, and few studies have examined sevelamer carbonate therapy in other ethnic nondialysis CKD patients. This study assessed the efficacy and safety of sevelamer carbonate in Chinese nondialysis CKD patients with hyperphosphatemia., Methods: The multicenter, randomized, double-blind, parallel-group, placebo-controlled, and phase 3 clinical trial enrolled 202 Chinese nondialysis CKD patients with serum phosphorus ≥1.78 mmol/L. Patients were randomly assigned 1:1 to receive sevelamer carbonate (2.4-12 g per day) or placebo for 8 weeks. The primary outcome was the change in serum phosphorous between baseline and week 8., Results: Totally 482 Chinese patients were screened and 202 were randomized (sevelamer carbonate, n = 101; placebo, n = 101). The mean serum phosphorous decreased significantly in patients treated with sevelamer carbonate compared with placebo (-0.22 ± 0.47 vs. 0.05 ± 0.44 mmol/L, p < 0.0001). Significantly ( p < 0.0001), decreases of serum total cholesterol, low-density lipoprotein cholesterol, and calcium-phosphorus (Ca × P) product levels from baseline to week 8 were shown in sevelamer carbonate group compared with placebo group. Serum intact parathyroid hormone was not significantly changed in the sevelamer carbonate group ( p = 0.83). Patients in the sevelamer carbonate group experienced similar adverse events as the placebo group., Conclusion: Sevelamer carbonate is an effective and well-tolerated phosphate binder in advanced nondialysis CKD Chinese patients with hyperphosphatemia., Competing Interests: The authors declare that they have no relevant financial interests., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Recent studies have shown that the gut microbiome changes brain function, behavior, and psychiatric and neurological disorders. The Gut-Brain Axis (GBA) provides a neuronal pathway to explain this. But exactly how do commensal bacteria signal through the epithelial layer of the large intestine to activate GBA nerve afferents? An in vitro model is described. We differentiated two human cell lines: Caco2Bbe1 into mature epithelium on 0.4-micron filters and then SH-SY5Y into mature neurons in 24-well plates. These were co-cultured by placing the epithelium-laden filters 1 mm above the neurons. Twenty-four hours later they were tri-cultured by apical addition of 10 7 Lactobacillus rhamnosus or Lactobacillus fermentum which settled on the epithelium. Alone, the Caco2bbe1 cells stimulated neurite outgrowth in underlying SH-SY5Y . Beyond this, the lactobacilli were well tolerated and stimulated further neurite outgrowth by 24 h post-treatment, though not passing through the filters. The results provide face validity for a first-of-kind model of transepithelial intestinal lumen-to nerve signaling. The model displays the tight junctional barrier characteristics found in the large intestine while at the same time translating stimulatory signals from the bacteria through epithelial cells to attracted neurons. The model is easy to set-up with components widely available.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gu, Tang, Wan, Zou, Lu, Zhu, Sheng, Wang, Liu, Yang and Hong.)

Aluminum (Al) toxicity is one of the key factors limiting crop production in acid soils; however, little is known about its transcriptional regulation in plants. In this study, we characterized the role of a NAM, ATAF1/2, and cup-shaped cotyledon 2 (NAC) transcription factors (TFs), ANAC017, in the regulation of Al tolerance in Arabidopsis (Arabidopsis thaliana). ANAC017 was localized in the nucleus and exhibited constitutive expression in the root, stem, leaf, flower, and silique, although its expression and protein accumulation were repressed by Al stress. Loss of function of ANAC017 enhanced Al tolerance when compared with wild-type Col-0 and was accompanied by lower root and root cell wall Al content. Furthermore, both hemicellulose and xyloglucan content decreased in the anac017 mutants, indicating the possible interaction between ANAC017 and xyloglucan endotransglucosylase/hydrolase (XTH). Interestingly, the expression of XTH31, which is responsible for xyloglucan modification, was downregulated in the anac017 mutants regardless of Al supply, supporting the possible interaction between ANAC017 and XTH31. Yeast one-hybrid, dual-luciferase reporter assay, and chromatin immunoprecipitation-quantitative PCR analysis revealed that ANAC017 positively regulated the expression of XTH31 through directly binding to the XTH31 promoter region, and overexpression of XTH31 in the anac017 mutant background rescued its Al-tolerance phenotype. In conclusion, we identified that the tTF ANAC017 acts upstream of XTH31 to regulate Al tolerance in Arabidopsis., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

Objective: To explore the effect of human bone marrow mesenchymal stem cells(MSC) on the steroid resistance of human airway epithelial cells. Methods: Ovalbumin (OVA)/lipopolysaccharide (LPS) were used to construct steroid resistant BEAS-2B cells, which were then co-cultured with MSC. Groups were set as follows: blank group, model group, Glucocorticoid group, MSC group, MSC+Glucocorticoid group (MSC+bud group). The expression of interleukin (IL)-8 in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA); the expression of reactive oxygen species (ROS) in the cells was detected by flow cytometry; the expression of glucocorticoid receptor α (GRα) and histone deacetylase 2 (HDAC2) protein in the cell was detected by Western blotting; and the expression of GRα and HDAC2 mRNA was detected by reverse transcription-polymerase chain reaction (RTPCR). Results: The expression level of IL-8 in the MSC group was significantly lower than that in the Glucocorticoid group (31.7±0.7 vs. 49.8±3.6, P <0.01). The expression of ROS in the MSC group was significantly lower than that in the Glucocorticoid group (2754±154 vs. 4624±228, P <0.05). The expression level of HDAC2 mRNA in the MSC group was significantly higher than that in the Glucocorticoid group(1.749±0.005 vs. 1.283±0.098, P <0.05). The expression level of GRα mRNA in the MSC group was significantly higher than that in the Glucocorticoid group (1.623±0.079 vs. 1.047±0.220, P <0.01). The expression of HDAC2 protein in the MSC group was significantly higher than that in the Glucocorticoid group (1.067±0.100 vs. 0.620±0.083, P <0.01). The expression of GRα protein in the MSC group was significantly higher than that in the Glucocorticoid group (0.834±0.053 vs. 0.579±0.017, P <0.01). ROS was positively correlated with the IL-8 expression ( r =0.796, P <0.01) and negatively correlated with the HDAC2 and GRα mRNA expression ( r =-0.893 3, P <0.01; r =0.931 4, P <0.01, respectively), as well as the HDAC2 and GRα Protein expression ( r =-0.929 5, P <0.01; r =-0.864 3, P <0.01, respectively). Conclusions: Human MSC can improve steroid resistance of airway epithelial cells in an exocrine manner. The mechanism may be related to the down-regulation of ROS and up-regulation of HDAC2, which lead to GRα overexpression. In addition, MSC may improve the steroid resistance by reducing the expression of IL-8.

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus . A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus , whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus ., Competing Interests: The authors declare that they have no competing interests., (© 2021 Wan et al.)

Background: The role of calcitriol (1,25-dihydroxyvitamin D 3 or 1,25-(OH) 2 D 3 ) in physiological processes, such as anti-fibrosis, anti-inflammation, and immunoregulation is known; however, its role in the remodeling of the glomerular capillary endothelium in rats with chronic renal failure (CRF) remains unclear., Methods: Here, we analyzed the role/number of endothelial progenitor cells (EPCs), renal function, and pathological alterations in rats with CRF, and compared the results before and after supplementation with calcitriol in vivo., Results: Amongst the three experimental groups (sham group, CRF group, and calcitriol-treated group (0.03 μg/kg/d), we observed substantially elevated cell adhesion and vasculogenesis in vivo in the calcitriol-treated group. Additionally, lower levels of serum creatinine (Scr) and blood urea nitrogen (BUN) was recorded in the calcitriol-treated group than the CRF group (p > 0.05). Calcitriol treatment also resulted in an improvement in renal pathological injury., Conclusions: Thus, calcitriol could ameliorate the damage of glomerular arterial structural and renal tubules vascular network integrity, maybe through regulating the number and function of EPCs in the peripheral blood of CRF rats. Treatment with it may improve outcomes in patients with renal insufficiency or combined cardiac insufficiency. Calcitriol could ameliorate CRF-induced renal pathological injury and renal dysfunction by remodeling of the glomerular capillary endothelium, thus, improving the function of glomerular endothelial cells., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Compulsive drug use despite adverse consequences defines addiction. While mesolimbic dopamine signaling is sufficient to drive compulsion, psychostimulants such as cocaine also boost extracellular serotonin (5-HT) by inhibiting reuptake. We used SERT Met172 knockin (SertKI) mice carrying a transporter that no longer binds cocaine to abolish 5-HT transients during drug self-administration. SertKI mice showed an enhanced transition to compulsion. Conversely, pharmacologically elevating 5-HT reversed the inherently high rate of compulsion transition with optogenetic dopamine self-stimulation. The bidirectional effect on behavior is explained by presynaptic depression of orbitofrontal cortex–to–dorsal striatum synapses induced by 5-HT via 5-HT 1B receptors. Consequently, in projection-specific 5-HT 1B receptor knockout mice, the fraction of individuals compulsively self-administering cocaine was elevated.

Background: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk., Methods: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny., Results: Identification of three novel loci (rs6427389 on 1q23.1 [ P =8.18×10 -9 , OR=1.132], rs6942325 on 6p25.3 [ P =1.62×10 -11 , OR=1.165], and rs2240335 on 1p36.13 [ P =5.10×10 -9 , OR=1.114]), implicates FCRL3 , DUSP22.IRF4 , and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4 , and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3 . Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA&#95;DRB1&#95;140&#95;32657458&#95;T, and AA&#95;DQA1&#95;34&#95;32717152) and two SNPs (rs9275464 and rs2295119)., Conclusions: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations., (Copyright © 2020 by the American Society of Nephrology.)

Recent studies suggested that serum secretory phospholipase A2 group IB (sPLA2-IB) was increased in idiopathic membranous nephropathy (IMN). However, the interference of high lipemia on the sPLA2-IB levels was not taken into account in these studies. The present study aimed to investigate the correlation between sPLA2-IB and lipemia, and the clinical merit of sPLA2-IB in the prediction of prognosis of IMN patients. A total of 64 IMN patients, 39 immunoglobulin A nephropathy (IgAN) patients and 64 healthy controls were included in the study. The levels of serum sPLA2-IB, lipemia and proteinuria were measured. Fifty IMN patients were followed up for 6 months. Pathologic stages were made for all IgAN and IMN patients. The results showed that the levels of serum sPLA2-IB, cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly higher, and the levels of albumin and high-density lipoprotein cholesterol (HDL-C) were significantly lower in IMN patients than in healthy controls and IgAN patients. Serum sPLA2-IB levels were also found to be higher in IgAN patients than in heathy controls, but the association of serum sPLA2-IB levels with proteinuria, cholesterol and albumin was only shown in IMN patients. Antibody against M-type receptor for secretory phospholipase A2 (PLA2R1) was positive in 81.3% IMN patients. Glomerular sPLA2-IB deposition, podocyte fused processes, and density deposition on thickened basement membrane were seen in IMN patients, but not in IgAN patients. IMN patients with lower sPLA2-IB and proteinuria levels were found to have better outcome after the 6-month follow-up. In IMN patients, sPLA2-IB levels were significantly increased in both serum and renal tissue. In conclusion, serum sPLA2-IB was closely correlated with proteinuria, albumin and cholesterol, and IMN patients with lower sPLA2-IB levels were more likely to achieve a better outcome.

Nonalcoholic fatty liver disease (NAFLD) poses serious threats to humans. Several studies have studied the biomarkers associated with NAFLD; however, the results vary because of the differences in the sequencing platform, sample selection, and filter conditions. This study aimed to explore the key microRNAs (miRNAs) of NAFLD by a systematic bioinformatics analysis. A total of 10 qualified NAFLD miRNA data sets were selected through a literature review. Signature miRNAs were identified by overlap comparison. The target genes of miRNAs were predicted by TargetScan software and functional enrichment, and transcription factor (TF) binding analysis of target genes was carried out by the database for annotation, visualization, and integrated discovery and Tfacts database, respectively. A total of three upregulated miRNAs and five downregulated miRNAs were identified in the NAFLD tissue. The target genes of upregulated miRNAs mainly enriched in the RNA polymerase II promoter transcriptional regulation, chromatin remodeling process, and O-glycan synthesis, circadian rhythm, and endocytosis; the target genes of downregulated miRNAs mainly enriched in the transcriptional regulation of DNA as a template, negative regulation process of protein phosphorylation, and Fc epsilon RI signaling pathways, Ras signaling pathways and the interaction between cytokines and cytokines. Besides, 136 interactions were formed between 62 TFs and 45 target genes of upregulated miRNA, whereas 157 interactions were formed between 72 TFs and 45 target genes of downregulated miRNA. Both contained 102 TFs, and 32 TFs were present in both target genes. To summarize, we identified an eight-miRNA set as a signature for NAFLD, which will benefit the clinical treatment of NAFLD., (© 2019 Wiley Periodicals, Inc.)

Regulation of α-glucosidase (EC 3.2.1.20) and its inhibitors is of great interest to researchers due to its clinical relevance as a target enzyme for the treatment of α-glucosidase-mediated diseases, such as type 2 diabetes mellitus and Pompe disease. In this study, we conducted a phloroglucinol-induced inhibition kinetics assay and performed computational molecular dynamics (MD) simulations to assess binding manner in α-glucosidase. The results showed that phloroglucinol reversibly inhibited α-glucosidase in a dose-dependent but non-competitive manner (K i =2.07±0.16mM). Interestingly, the maximum peak wavelength and the hydrophobic surface remained unchanged during the inhibition reaction, with computational MD simulations further revealing that phloroglucinol bound in front of the active site pocket rather than in the α-glucosidase active site. Therefore, we speculate that phloroglucinol-specific inhibition is mild and the inhibitor likely binds to a single binding site near but not in the active site. Our study provided insight into the effects and mechanisms associated with a mild inhibitor of α-glucosidase activity and promotes fundamental research and potential applications of inhibitors for treatment of α-glucosidase-mediated clinical disease., (Copyright © 2018. Published by Elsevier B.V.)

Although xyloglucan (XyG) is reported to bind Aluminium (Al), the influence of XyG fucosylation on the cell wall Al binding capacity and plant Al stress responses is unclear. We show that Arabidopsis T-DNA insertion mutants with reduced AXY3 (XYLOSIDASE1) function and consequent reduced levels of fucosylated XyG are more sensitive to Al than wild-type Col-0 (WT). In contrast, T-DNA insertion mutants with reduced AXY8 (FUC95A) function and consequent increased levels of fucosylated XyG are more Al resistant. AXY3 transcript levels are strongly down regulated in response to 30 min Al treatment, whilst AXY8 transcript levels also repressed until 6 h following treatment onset. Mutants lacking AXY3 or AXY8 function exhibit opposing effects on Al contents of root cell wall and cell wall hemicellulose components. However, there was no difference in the amount of Al retained in the pectin components between mutants and WT. Finally, whilst the total sugar content of the hemicellulose fraction did not change, the altered hemicellulose Al content of the mutants is shown to be a likely consequence of their different XyG fucosylation levels. We conclude that variation in XyG fucosylation levels influences the Al sensitivity of Arabidopsis by affecting the Al-binding capacity of hemicellulose.

Background/aims: A lack of baseline serum creatinine (SCr) data leads to underestimation of the burden caused by acute kidney injury (AKI) in developing countries. The goal of this study was to investigate the effects of various baseline SCr analysis methods on the current diagnosis of AKI in hospitalized patients., Methods: Patients with at least one SCr value during their hospital stay between January 1, 2011 and December 31, 2012 were retrospectively included in the study. The baseline SCr was determined either by the minimum SCr (SCrMIN) or the estimated SCr using the MDRD formula (SCrGFR-75). We also used the dynamic baseline SCr (SCrdynamic) in accordance with the 7 day/48 hour time window. AKI was defined based on the KDIGO SCr criteria., Results: Of 562,733 hospitalized patients, 350,458 (62.3%) had at least one SCr determination, and 146,185 (26.0%) had repeat SCr tests. AKI was diagnosed in 13,883 (2.5%) patients using the SCrMIN, 21,281 (3.8%) using the SCrGFR-75 and 9,288 (1.7%) using the SCrdynamic. Compared with the non-AKI patients, AKI patients had a higher in-hospital mortality rate regardless of the baseline SCr analysis method., Conclusions: Because of the scarcity of SCr data, imputation of the baseline SCr is necessary to remedy the missing data. The detection rate of AKI varies depending on the different imputation methods. SCrGFR-75 can identify more AKI cases than the other two methods., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Recent studies have indicated that long non-coding RNAs (lncRNAs) play important regulatory roles in tumor development and progression. However, the contribution of small nucleolar RNA host gene 20 (SNHG20) to gastric cancer development remains largely unknown. The aim of the study is to investigate the functional significance of SNHG20 involved in gastric cancer (GC) progression. In the study, our results demonstrated that the expression levels of SNHG20 were remarkably up-regulated in GC cells. Functionally, SNHG20 promoted the GC MKN45 and BGC-823 cells proliferation and invasion. Furthermore, knockdown of SNHG20 significantly inhibited the epithelial-mesenchymal transition (EMT) in MKN45 and BGC-823 cells, whereas, the overexpression of SNHG20 had the promoting effects. Moreover, we found that overexpression of SNHG20 in MKN45 and BGC-823 cells significantly inhibited the expression of E-cadherin and p21 via binding to EZH2 and regulated the GSK-3β/β-catenin signaling pathway. Thus, the results showed that SNHG20 acted as an oncogene in GC and targeting SNHG20 may serve as a therapeutic target for GC., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests.

Glucuronoxylan (GX), an important component of hemicellulose in the cell wall, appears to affect aluminium (Al) sensitivity in plants. To investigate the role of GX in cell-wall-localized xylan, we examined the Arabidopsis thaliana parvus mutant in detail. This mutant lacks α-D-glucuronic acid (GlcA) side chains in GX and has greater resistance to Al stress than wild-type (WT) plants. The parvus mutant accumulated lower levels of Al in its roots and cell walls than WT despite having cell wall pectin content and pectin methylesterase (PME) activity similar to those of WT. Our results suggest that the altered properties of hemicellulose in the mutant contribute to its decreased Al accumulation. Although we observed almost no differences in hemicellulose content between parvus and WT under control conditions, less Al was retained in parvus hemicellulose than in WT. This observation is consistent with the finding that GlcA substitutions in WT GX, but not mutant GX, were increased under Al stress. Taken together, these results suggest that the modulation of GlcA levels in GX affects Al resistance by influencing the Al binding capacity of the root cell wall in Arabidopsis., (© 2017 John Wiley & Sons Ltd.)

Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

It is to establish the normal range and investigate the distribution characteristics of serum Insulin-like growth factor-1 (IGF-1) for healthy adults in southern China. IGF-1 levels of 515 healthy adults (254 males and 261 females) were measured by automated chemiluminescence immunoassay. The subjects were strictly selected healthy volunteers, aged 20 to 84 years old, with equal five year intervals and without abnormal conditions that impacted IGF-1 levels. The reference ranges were calculated using the smooth centile curves of the LMS method (L: coefficient of skewness, M: median, S: coefficient of variation). IGF-1 declined with aging in adults. There were statistically significant differences for the IGF-1 levels between men and women in some subgroups of age. Gender differences varied depending on the age. Middle-aged females had higher IGF-1 whilst elder females had lower IGF-1. The statistical differences were seen in three subgroups of age between this study and a German cohort that is the reference range for the laboratory test kit. Here, the age- and gender-specific normal range was established for Chinese adults. A Z Score of IGF-1 for an individual could be obtained via the LMSchartmaker application, which standardized IGF-1 research worldwide.

Objective: To compare the level of testosterone between type-2 diabetes mellitus (T2DM) patients and healthy controls and to investigate the status of hypogonadism and the influence of hypopgonadism on the quality of life., Methods: We collected serum total testosterone (TT), free testosterone (FT), sex hormone-binding globulin (SHBG), and other clinical data from 166 T2DM patients aged over 30 years and 186 age-matched healthy controls. We investigated the quality of life (QoL) of the two groups of subjects using the questionnaires of Androgen Deficiency in Aging Males (ADAM), Aging Male Symptoms (AMS), 36-Item Short-Form Health Survey (SF-36), and Special Quality of Life for Diabetes Mellitus (DSQL)., Results: The level of calculated FT (cFT) was remarkably lower in the T2DM patients than in the healthy controls (P<0.05), but no statistically significant differences were observed between the two groups in the levels of TT, bio-available testosterone (Bio-T), and SHBG. The T2DM males with hypogonadism showed significant differences from those without in age, height, systolic blood pressure, and creatinine (P<0.05). Based on the criteria of cFT <0.3 nmol/L and AMS score ≥27, the incidence rate of hypogonadism was 51.81% in the T2DM patients, 31.58% in the 30－39 yr group, 32.50% in the 40－49 yr group, 50% in the 50－59 yr group, 69.23% in the 60－69 yr group, and 77.27% in the ≥70 yr group, elevated by 77.4% with the increase of 10 years of age (OR = 1.774, P<0.001). The AMS score was significantly correlated with the scores of DSQL (r = 0.557, P<0.001) and SF-36 (r = －0.739, P<0.001) in the T2DM patients., Conclusions: T2DM patients have lower levels of cFT than healthy men, accompanied with a higher incidence of hypogonadism. Age is a main risk factor of hypogonadism. Severer testosterone deficiency symptoms are associated with lower scores of QoL in T2DM males.

Objective: To evaluate the efficacy and safety of calcitriol in the prevention and treatment of glucocorticoid-induced osteoporosis., Methods: 66 patients treated with glucocorticoids (GC) for primary nephrotic syndrome (NS) were randomly assigned to 3 groups. Groups were designated as follows: calcitriol alone (n = 22), calcitriol plus calcium carbonate (n = 23), or calcium carbonate alone (n = 21). Serum markers of bone metabolism and bone mineral density (BMD) were tested at 3 different time points: the initiation of GC treatment (baseline), 12 weeks, and 24 weeks after the initiation of treatment., Results: Levels of serum 25-hydroxy vitamin D, serum osteocalcin, and total serum collagen type N-terminal extension of the peptide were significantly decreased following GC therapy (p < 0.05). β-collagen serum-specific sequences were significantly increased following GC therapy. The above-mentioned changes were less dramatic in patients treated with calcitriol, although the differences were significant (p < 0.05). Changes in serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (PTH) were not significant. 24 weeks after the initiation of treatment, BMD of the lumbar spine and femoral bone significantly decreased in all of 3 groups. However, patients who received calcitriol had significantly higher BMD of the lumbar spine than patients who received calcium carbonate alone (calcitriol plus calcium carbonate vs. calcium carbonate alone: 0.82 ± 0.19 g/cm2 vs. 0.62 ± 0.23 g/cm2 p < 0.05; calcitriol vs. calcium carbonate alone 0.805 ± 0.203 g/cm2 vs. 0.615 ± 0.225 g/cm2 p < 0.05), respectively. No serious adverse events were observed., Conclusion: Calcitriol may be more effective than calcium carbonate in preventing and treating GC-induced osteoporosis in patients with NS.

Glucose (Glu) is involved in not only plant physiological and developmental events but also plant responses to abiotic stresses. Here, we found that the exogenous Glu improved root and shoot growth, reduced shoot cadmium (Cd) concentration, and rescued Cd-induced chlorosis in Arabidopsis thaliana (Columbia ecotype, Col-0) under Cd stressed conditions. Glucose increased Cd retained in the roots, thus reducing its translocation from root to shoot significantly. The most Cd retained in the roots was found in the hemicellulose 1. Glucose combined with Cd (Glu + Cd) treatment did not affect the content of pectin and its binding capacity of Cd while it increased the content of hemicelluloses 1 and the amount of Cd retained in it significantly. Furthermore, Leadmium Green staining indicated that more Cd was compartmented into vacuoles in Glu + Cd treatment compared with Cd treatment alone, which was in accordance with the significant upregulation of the expression of tonoplast-localized metal transporter genes, suggesting that compartmentation of Cd into vacuoles also contributes to the Glu-alleviated Cd toxicity. Taken together, we demonstrated that Glu-alleviated Cd toxicity is mediated through increasing Cd fixation in the root cell wall and sequestration into the vacuoles., (© 2014 Institute of Botany, Chinese Academy of Sciences.)

Objective: To investigate the prevalence of obesity in young adults and to analyze the influencing factors on renal functions and proteinuria in this population., Methods: This study comprised civil servants between 20 and 39 years old, who received physical examinations at the First Affiliated Hospital of Fujian Medical University. The subjects were categorized into four groups based on age (20-24, 25-29, 30-34 and 35-39 years) and the number of risk factors they had (hypertension, dyslipidemia, hyperglycemia and hyperuricemia). The relationships between obesity and the prevalence of proteinuria, between obesity and risk factors and between estimated glomerular filtration rate (eGFR) and proteinuria were analyzed., Results: Among the 2293 young civil servants, in men the prevalence of obesity was 33.3 % and proteinuria was 2.5 %. However in women the prevalence of obesity and proteinuria was 7.5 % and 1.7 %, respectively. The levels of blood pressure, serum uric acid (UA), cholesterol (TC), triglyceride (TG), fasting glucose (FBG) and low-density lipoprotein cholesterol (LDL-C) were lower and the level of serum high-density lipoprotein cholesterol (HDL-C) was higher in nonobese groups compared with obese groups. There were no significant differences in eGFR between the two groups. The eGFR in male subjects was associated with age, UA, body mass index (BMI), FBG, TC, TG, LDL and HDL, and in female subjects associated with UA, age, BMI, diastolic blood pressure, FBG and LDL. BMI in both males and females increased with the higher number of risk factors. Multiple regression analysis revealed that hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors. Obesity, blood pressure, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with proteinuria., Conclusion: Obesity can pose an independent risk factor for proteinuria in young adults. Hypertension, dyslipidemia, hyperglycemia and hyperuricemia were independently associated with obesity. eGFR decreased with a higher number of risk factors.

Plants growing in phosphorus (P)-deficient conditions can either increase their exploration of the environment (hence increasing P uptake) or can solubilize and reutilize P from established tissue sources. However, it is currently unclear if P stored in root cell wall can be reutilized. The present study shows that culture of the rice cultivars 'Nipponbare' (Nip) and 'Kasalath' (Kas) in P-deficient conditions results in progressive reductions in root soluble inorganic phosphate (Pi). However, Nip consistently maintains a higher level of soluble Pi and lower relative cell wall P content than does Kas, indicating that more cell wall P is released in Nip than in Kas. P-deficient Nip has a greater pectin and hemicellulose 1 (HC1) content than does P-deficient Kas, consistent with the significant positive relationship between pectin and root-soluble Pi levels amongst multiple rice cultivars. These observations suggest that increased soluble Pi might result from increased pectin content during P starvation. In vitro experiments showed that pectin releases Pi from insoluble FePO4. Furthermore, an Arabidopsis thaliana mutant with reduced pectin levels (qua1-2), has less root soluble Pi and is more sensitive to P deficiency than the wild type (WT) Col-0, whereas NaCl-treated WT plants exhibit both an increased root pectin content and an elevated soluble Pi content during P-starvation. These observations indicate that pectin can facilitate the remobilization of P deposited in the cell wall. This is a previously unknown mechanism for the reutilization of P in P-starved plants., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Xyloglucan (XyG) has been reported to contribute to the aluminum (Al)-binding capacity of the cell wall in Arabidopsis (Arabidopsis thaliana). However, the influence of O-acetylation of XyG, accomplished by the putative O-acetyltransferase TRICHOME BIREFRINGENCE-LIKE27 (TBL27 [AXY4]), on its Al-binding capacity is not known. In this study, we found that the two corresponding TBL27 mutants, axy4-1 and axy4-3, were more Al sensitive than wild-type Columbia-0 plants. TBL27 was expressed in roots as well as in leaves, stems, flowers, and siliques. Upon Al treatment, even within 30 min, TBL27 transcript accumulation was strongly down-regulated. The mutants axy4-1 and axy4-3 accumulated significantly more Al in the root and wall, which could not be correlated with pectin content or pectin methylesterase activity, as no difference in the mutants was observed compared with the wild type when exposed to Al stress. The increased Al accumulation in the wall of the mutants was found to be in the hemicellulose fraction. While the total sugar content of the hemicellulose fraction did not change, the O-acetylation level of XyG was reduced by Al treatment. Taken together, we conclude that modulation of the O-acetylation level of XyG influences the Al sensitivity in Arabidopsis by affecting the Al-binding capacity in the hemicellulose., (© 2014 American Society of Plant Biologists. All Rights Reserved.)

Previously, we reported that although the Arabidopsis (Arabidopsis thaliana) Xyloglucan Endotransglucosylase-Hydrolase31 (XTH31) has predominately xyloglucan endohydrolase activity in vitro, loss of XTH31 results in remarkably reduced in vivo xyloglucan endotransglucosylase (XET) action and enhanced Al resistance. Here, we report that XTH17, predicted to have XET activity, binds XTH31 in yeast (Saccharomyces cerevisiae) two-hybrid and coimmunoprecipitations assays and that this interaction may be required for XTH17 XET activity in planta. XTH17 and XTH31 may be colocalized in plant cells because tagged XTH17 fusion proteins, like XTH31 fusion proteins, appear to target to the plasma membrane. XTH17 expression, like that of XTH31, was substantially reduced in the presence of aluminum (Al), even at concentrations as low as 10 µm for 24 h or 25 µm for just 30 min. Agrobacterium tumefaciens-mediated transfer DNA insertion mutant of XTH17, xth17, showed low XET action and had moderately shorter roots than the wild type but was more Al resistant than the wild type. Similar to xth31, xth17 had low hemicellulose content and retained less Al in the cell wall. These data suggest a model whereby XTH17 and XTH31 may exist as a dimer at the plasma membrane to confer in vivo XET action, which modulates cell wall Al-binding capacity and thereby affects Al sensitivity in Arabidopsis., (© 2014 American Society of Plant Biologists. All Rights Reserved.)

Objective: To evaluate the clinical efficacy and safety of sequential treatment with alprostadil and beraprost sodium for chronic renal failure caused by chronic glomerulonephritis., Methods: Sixty-three patients with chronic renal failure due to chronic glomerulonephritis, after receiving a 2-week-long conventional treatment, were randomly divided into alprostadil group (n=20, with alprostadil injection at 10 µg/d for 2 weeks), sequential treatment group (n=21, with alprostadil injection at 10 µg/d for 2 weeks and oral beraprost sodium at 20 µg three times a day for 12 weeks), and strengthened sequential treatment group (n=22, with alprostadil injection at 20 µg/d for 2 weeks and a double dose of oral beraprost sodium for 12 weeks). Urinary albumin excretion rate (UAER), cystatin C (Cys C), blood urea nitrogen, creatinine, fibrinogen, D-dimer, prothrombin time (PT), and platelets were tested before and after the treatment, and the changes in urinary albumin discharge rate, serum creatinine, and glomerular filtration rate were determined., Results: The patients in strengthened sequential treatment group showed a significantly decreased change rate of urinary albumin discharge rate (P<0.01) than those in the other two groups. In the two sequential treatment groups, especially the strengthened treatment group, the change rate of glomerular filtration rate increased significantly compared with that in alprostadil group (P<0.01). Strengthened sequential treatment resulted also in significantly decreased increment of serum creatinine compared that in the other 2 groups (P<0.01). After 14 weeks of treatment, fibrinogen and D-dimer were decreased in all the 3 groups (P<0.05) to a comparable level between the 3 groups (P>0.05), and prothrombin time (PT) or platelet showed no significant changes (P>0.05)., Conclusion: Sequential treatment with alprostadil and beraprost sodium can improve the glomerular filtration rate and decrease urine albumin excretion rate, serum creatinine increase rate, and lower blood fibrinogen and D-dimer levels, thus delaying the progression of chronic renal failure caused by chronic glomerulonephritis. This therapy shows a dose-related effect with good clinical safety.

Background: Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China., Methods: The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients., Results: The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05)., Conclusions: The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Previously, we identified the genetic variant -241 (-/G) (rs11453459) in the PP2A-Aα gene (PPP2R1A) promoter and demonstrated that this variant influences the DNA-binding affinity of nuclear factor-kappa B (NF-κB). In this study, we further confirmed that the transcriptional activity of PPP2R1A may be regulated by NF-κB through the functional genetic variant -241 (-/G). Moreover, we also demonstrated that the methylation status of CpG islands in the promoter of PPP2R1A influences the activity of this gene promoter. Few studies have examined the role of this -241 (-/G) variant in genetic or epigenetic regulation in hepatocellular carcinoma (HCC). To investigate whether this functional variant in the PPP2R1A promoter is associated with the risk of HCC and confirm the function of the -241 (-/G) variant in the HCC population, we conducted a case-control study involving 251 HCC cases and 252 cancer-free controls from a Han population in southern China. Compared with the -241 (--) homozygote, the heterozygous -241 (-G) genotype (adjusted OR  = 0.32, 95% confidence interval (CI)  = 0.17-0.58, P<0.001) and the -241 (-G)/(GG) genotypes (adjusted OR  = 0.38, 95% CI  = 0.22-0.67, P  = 0.001) were both significantly associated with a reduced risk of HCC. Stratification analysis indicated that the protective role of -241 (-G) was more pronounced in individuals who were ≤ 40 years of age, female and HBV-negative. Our data suggest that the transcriptional activity of PPP2R1A is regulated by NF-κB through the -241 (-/G) variant and by the methylation of the promoter region. Moreover, the functional -241 (-/G) variant in the PPP2R1A promoter contributes to the decreased risk of HCC. These findings contribute novel information regarding the gene transcription of PPP2R1A regulated by the polymorphism and methylation in the promoter region through genetic and epigenetic mechanisms in hepatocarcinogenesis.

Objective: We investigated how cells respond to the induction of DNA damage, focusing specifically on mRNA expression levels of cell regulatory and DNA repair genes under exposure to benzene., Method: The study sample was classified into three groups: direct exposure to benzene (A), indirect exposure to benzene (B), and non-exposed (C). Concentrations of benzene in the air of workplaces were monitored. Further blood biochemical parameters, cell cycle-regulated and DNA damage-related genes expression were analyzed., Results: The mRNA expression levels of Apel, Rad51, Bcl-2, Bax, Xpa, and Xpc genes were significantly down-regulated in groups A and B, with a dramatic up-regulation of p21 gene in group A accompanied by significantly lower counts of white blood cells, hemoglobin, platelets and lymphocyte subsets of CD8+, CD4+, T and B cells., Conclusion: The results indicated that exposure to benzene had significantly altered mRNA expression of some critical cell regulatory and DNA repair genes.

Objective: To study whether alisol B could inhibit complement 3a (C3a) induced renal tubular epithelial-mesenchymal transition (EMT)., Methods: The in vitro cultured human renal tubular epithelial HK-2 cells were intervened with 5 ng/mL transforming growth factor-beta (TGF-beta), 0.1 micromol C3a, and 0.1 micromol C3a + 10 micromol alisol B, respectively. The mRNA and protein expressions of alpha-SMA, E-cadherin, and C3 were detected using RT-PCR, Western blot, and immunofluorescence, respectively., Results: The mRNA and protein expressions of C3 in HK-2 cells were up-regulated after intervention of C3a (P < 0.01), the mRNA and protein expressions of alpha-SMA in HK-2 cells were obviously enhanced (P < 0.01), the mRNA and protein expressions of E-cadherin obviously decreased (P < 0.01). When compared with the group intervened by exogenous C3a, after intervention of alisol B, the mRNA and protein expressions of alpha-SMA in HK-2 cells were obviously reduced (P < 0.01), the mRNA and protein expressions of E-cadherin obviously increased (P < 0.05)., Conclusions: Exogenous C3a could induce renal tubular EMT. Alisol B was capable of suppressing C3a induced EMT.

The possibility of differentiating bone marrow-derived mesenchymal stem cells (BMSCs) into tubular epithelial-like cells is explored in vitro. Purified BMSCs from Sprague-Dawley rats were obtained by density gradient centrifugation. Third generation BMSCs were divided into six groups and were cultured under different conditions. The expression of alkaline phosphatase and cytokeratin (CK)-18 protein was detected through staining and immunocytochemistry, respectively, and the expression of E-cadherin proteins was recorded through immunofluorescence. Some cells in ischemia/reperfusion (I/R), all-trans retinoic acid (ATRA), epidermal growth factor (EGF) and bone morphogenetic protein-7 (BMP-7) groups turned positive, whereas the positive cells in the combined group significantly increased compared with the other groups. Compared with the control group, the positive expression rates of CK-18 in the I/R, ATRA, EGF, BMP-7 and the combined group were 11·50% ± 3·84%, 27·40% ± 2·70%, 29·60% ± 4·51%, 26·80% ± 5·00% and 44·00% ± 3·16%, respectively, and CK-18 mRNA expression in the combined group was obviously higher than that in the other groups (P < 0·01). Immunofluorescence detection showed that E-cadherin expression was not detectable in the control group, whereas the positive expression rates of E-cadherin in the I/R, ATRA, EGF, BMP-7 and the combined group were 6·75% ± 2·13%, 16·40% ± 2·69%, 18·25% ± 3·50%, 16·06% ± 2·00% and 30·26% ± 5·16%, respectively. The addition of ATRA, EGF and BMP-7 induces BMSCs differentiation into tubular epithelial-like cells in stimulated acute renal failure microenvironment in vitro., (Copyright © 2011 John Wiley & Sons, Ltd.)

Serine-threonine protein phosphatase 2A (PP2A) is a trimeric holoenzyme that plays an integral role in the regulation of cell growth, differentiation, and apoptosis. The substrate specificity and (sub)cellular localization of the PP2A holoenzymes are highly regulated by interaction with a family of regulatory B subunits (PP2A-Bs). The regulatory subunit PP2A-B/PR55δ (PP2A-Bδ) is involving in the dephosphorylation of PP2A substrates and is crucial for controlling entry into and exit from mitosis. The molecular mechanisms involved in the regulation of expression of PP2A-Bδ gene (PPP2R2D) remain largely unknown. To explore genetic variations in the 5'-flanking region of PPP2R2D gene as well as their frequent haplotypes in the Han Chinese population and determine whether such variations have an impact on transcriptional activity, DNA samples were collected from 70 healthy Chinese donors and sequenced for identifying genetic variants in the 5'-flanking region of PPP2R2D. Four genetic variants were identified in the 1836 bp 5'-flanking region of PPP2R2D. Linkage disequilibrium (LD) patterns and haplotype profiles were constructed for the genetic variants. Using serially truncated human PPP2R2D promoter luciferase constructs, we found that a 601 bp (-540 nt to +61 nt) fragment constitutes the core promoter region. The subcloning of individual 5'-flanking fragment revealed the existence of three haplotypes in the distal promoter of PPP2R2D. The luciferase reporter assay showed that different haplotypes exhibited distinct promoter activities. The EMSA revealed that the -462 G>A variant influences DNA-protein interactions involving the nuclear factor 1 (NF1). In vitro reporter gene assay indicated that cotransfection of NF1/B expression plasmid could positively regulate the activity of PPP2R2D proximal promoter. Introduction of exogenous NF1/B expression plasmid further confirmed that the NF1 involves in the regulation of PPP2R2D gene expression. Our findings suggest that functional genetic variants and their haplotypes in the 5'-flanking region of PPP2R2D are critical for transcriptional regulation of PP2A-Bδ.

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

Objective: To assess complete remission (CR), the overall survival (OS), event-free survival (EFS) and adverse events of newly diagnosed acute promyelocytic leukemia (APL) with homoharringtonine (HHT) plus ATRA, to evaluate the therapeutic effect by comparing HHT plus ATRA with daunorubicin plus ATRA as induction regimen (HA with DA as post-remission regimen)., Methods: 115 APL patients (54 in HHT group, 61 in DNR group) after long-term follow-up were enrolled in the analyses of clinical feature, chromosome karyotype, molecular biology, OS and EFS., Results: The overall CR of 115 patients was 100%, the median interval to achieve hematological CR was 32 (22 - 43) days, the overall median OS was within 0.23 - 77.34 months, median EFS was within 0.23 - 77.34 months. 3-year OS rate was 93%, 5-year OS rate 93%, 3-year EFS rate 85% and 5-year RFS rate 75% respectively. Converting to PML-RARα PCR-negative after the induction therapy in the HHT and DNR group was 31.3% and 15.5% respectively, at the end of 1 consolidation course was 68.6% and 77.6% respectively, while the remaining 4 patients tested PML-RARα PCR-negative at the end of 2 consolidation courses in the DNR group. While both groups obtained the identical molecular biology relapse rate (9.8% and 8.6%, respectively). Survival analysis indicated that no significant difference was found on OS and EFS between the HHT group and the DNR group (P = 0.206 and 0.506). 5-year OS rate was 87% for the HHT group while 98% for the DNR group, 5-years EFS rate was 80% for the HHT group while 71% for the DNR group. And the risk group was not the factor affecting OS and EFS (P = 0.615 and 0.416). Grade 2 fever in the HHT group was less than in the DNR group during induction therapy. And no difference was found in terms of liver dysfunction, renal dysfunction, cardiac dysfunction, and hematologic toxicity between two groups., Conclusion: Our study demonstrated comparable therapeutic effect of HHT or DNR on APL. HHT was also well tolerated and didn't cause serious adverse events.

Objective: To explore the association of polymorphisms of metabolizing enzyme genes with chronic benzene poisoning (CBP) comprehensively by case-control design., Methods: 152 CBP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. 30 single nucleotide polymorphisms (SNPs) in 13 genes such as CYP2E1 were tested by PCR-RFLP, sequencing approaches. Logistic regression model was used to detect main effects and 2-order interaction effects of gene and/or environment. Multifactor dimensionality reduction (MDR) was used to detect high-order gene-gene or gene-environment interactions., Results: Based on logistic regression, the main effects of GSTP1 rs947894, EPHX1 rs1051740, CYP1A1 rs4646903, CYP2D6 rs1065852 and rs1135840 were found to be significant (P < 0.05) while the confounding factors of sex, cigarette smoking, alcohol consumption and the intensity of benzene exposure were controlled. EPHX1 rs1051740 might be associated with CBP (P = 0.06). There existed 3 types of interactions were as followed: interactions of GSTP1 rs947894 with alcohol consumption, CYP2E1 rs3813867 with EPHX1 rs3738047, EPHX1 rs3738047 with alcohol consumption(P < 0.05), while the main effects of CYP2E1 rs3813867 and EPHX1 rs3738047 were not significant (P > 0.05). The other SNPs did not show any significant associations with CBP. According to MDR, a 3-order interaction with the strongest combined effect was found, i.e. the 3-factor combination of CYP1A1 rs4646903, CYP2D6 rs1065852 and CYP2D6 rs1135840., Conclusion: Gene-gene, gene-environment interactions are important mechanism to genetic susceptibility of CBP.

Pyrrole-imidazole (PI) polyamide can bind to specific sequences in the minor groove of double-helical DNA and inhibit transcription of the genes. We designed and synthesized a PI polyamide to target the human connective tissue growth factor (hCTGF) promoter region adjacent to the Smads binding site. Among coupling activators that yield PI polyamides, 1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide hexafluorophosphate (HCTU) was most effective in total yields of PI polyamides. A gel shift assay showed that a PI polyamide designed specifically for hCTGF (PI polyamide to hCTGF) bound the appropriate double-stranded oligonucleotide. A fluorescein isothiocyanate (FITC)-conjugated PI polyamide to CTGF permeated cell membranes and accumulated in the nuclei of cultured human mesangial cells (HMCs) and remained there for 48 h. The PI polyamide to hCTGF significantly decreased phorbol 12-myristate acetate (PMA)- or transforming growth factor-β1 (TGF-β1)-stimulated luciferase activity of the hCTGF promoter in cultured HMCs. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated expression of hCTGF mRNA in a dose-dependent manner. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated levels of hCTGF protein in HMCs. These results indicate that the developed synthetic PI polyamide to hCTGF could be a novel gene silencer for fibrotic diseases.

This study aims to improve the tensile strength and elastic modulus of nano-apatite/poly(ε-caprolactone) composites by silane-modification of the nano-apatite fillers. Three silane coupling agents were used to modify the surfaces of nano-apatite particles and composites of silanized apatite and PCL were prepared by a technique incorporating solvent dispersion, melting-blend and hot-pressing. The results showed that the silane coupling agents successfully modified the surfaces of nano-apatite fillers, and the crystallization temperatures of the silanized apatite/PCL composites were the higher than that of the non-silanized control material, although the melting temperature of the composites remained almost unaffected by silanization. The ultimate tensile strength and elastic modulus of the silanized composites reached 22.60 MPa and 1.76 GPa, as a result of the improved interfacial bonding and uniform dispersion of nano-apatite fillers. This study shows that the processing technique and silanization of nano-apatite particles can effectively improve the tensile strength and elastic modulus of nano-apatite/PCL composites.

Objective: To study the safety and effect of simplified regional citrate anticoagulation (RCA) in continuous veno-venous hemofiltration (CVVH)., Methods: Fourteen patients were treated with CVVH using simplified RAC. Simplified anticoagulation protocol included the addition of 4% sodium citrate into the replacement fluid. The citrate replacement fluid was infused in a speed of 2,000 ml/h or 3,000 ml/h, and at the same time 10% calcium gluconate and 25% magnesium sulfate were infused post filter or with venous pump into peripheral veins. Serum electrolytes, arterial blood gas analysis, coagulation at the beginning and 4, 8, 12 hours after the treatment were monitored. Patient's general condition was observed carefully. After treatment, blood volume in the hollow fiber filter was measured., Results: Fourteen patients underwent altogether 34 times of this procedure for a total of 544 hours. Each treatment lasted 4-36 hours, with a mean of (16.0+/-7.5) hours. The filter was not changed for 30 procedures. After treatment, the blood volume in the filter was higher than 80% of the original volume. The life span of the filter was (14.79+/-5.98) hours on the average. Twelve hours after infusing citrate, there was a marked shortening of prothrombin time [PT, (12.2+/-1.2) s vs. (14.0+/-3.3) s], while plasma total calcium was increased markedly [(2.46+/-0.30) mmol/L vs. (2.07+/-0.36) mmol/L, both P<0.05]. There was no significant difference in activated partial thromboplastin time (APTT), thrombin time (TT), the concentration of Ca(2+) and Mg(2+), pH and base excess (BE). In one patient with hypoxemia the treatment was stopped due to the appearance of serious complications. No hypernatremia or metabolic alkalosis was found during the RCA in all the patients. No significant bleeding events attributed to RCA occurred., Conclusion: The simplified anticoagulation protocol by adding sodium citrate replacement fluid can be applied safely in replacement fluid>2,000 ml/h of CVVH without complications of hypernatremia and metabolic alkalosis caused by sodium citrate anticoagulation.