Novel spirooxindole alkaloid derivatives from the medicinal insect Blaps japanensis and their biological evaluation.

Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.

Five New Cantharidin Derivatives from the Insect Mylabris cichorii L. and Their Potential against Kidney Fibrosis In Vitro.

Five new monoterpenoids including three 1-hydroxymethyl-2-methyl cantharimide-type derivatives (1, 2, and 5) and two 1,2-dimethyl cantharimide-type derivatives (3 and 4), together with three known compounds (6-8) were isolated from the insect Mylabris cichorii Linnaeus. The structures of these new compounds, including their absolute configurations, were characterized by detailed analysis of NMR, chemical derivatization, and quantum chemical ECD calculations. All of the compounds were tested for their biological activity against kidney fibrosis. The results revealed that compounds 2, 4, and 7 could inhibit kidney fibrosis in vitro at 40 µM by inhibiting the expression of fibronectin and collagen I in TGF-ß1-induced NRK-52e cells.

Isobaric Stable Isotope N-Phosphorylation Labeling (iSIPL) for Ultrasensitive Proteome Quantification.

Stable isotope chemical labeling methods have been widely used for high-throughput mass spectrometry (MS)-based quantitative proteomics in biological and clinical applications. However, the existing methods are far from meeting the requirements for high sensitivity detection. In the present study, a novel isobaric stable isotope N-phosphorylation labeling (iSIPL) strategy was developed for quantitative proteome analysis. The tryptic peptides were selectively labeled with iSIPL tag to generate the novel reporter ions containing phosphoramidate P-N bond with high intensities under lower collision energies. iSIPL strategy are suitable for peptide sequencing and quantitative analysis with high sensitivity and accuracy even for samples of limited quantity. Furthermore, iSIPL coupled with affinity purification and mass spectrometry was applied to measure the dynamics of cyclin dependent kinase 9 (CDK9) interactomes during transactivation of the HIV-1 provirus. The interaction of CDK9 with PARP13 was found to significantly decrease during Tat-induced activation of HIV-1 gene transcription, suggesting the effectiveness of iSIPL strategy in dynamic analysis of protein-protein interaction in vivo. More than that, the proposed iSIPL strategy would facilitate large-scale accurate quantitative proteomics by increasing multiplexing capability.

Unusual sesquilignans with anti-inflammatory activities from the resin of Ferula sinkiangensis.

Sinkianlignans A - D (1-4), four new sesquilignans with an unusual architectures was characterized with a rarely α-γ', ß-γ', and γ-γ' linkage pattern, and sinkianlignans E - F (5 and 6), two lignans, were isolated from the Ferula sinkiangensis. Hypothetic biosynthetic pathway of compound 3 contain a newly formed six-membered C-ring by Diels-Alder cycloaddition. The structures of isolates were established by spectroscopic techniques and computational methods. Biological evaluation of all the isolated compounds revealed that compounds 2a and 2b could inhibit IL-6 and TNF-α production in lipopolysaccharide (LPS) induced RAW264.7 cells in a dose-dependent manner.

Urinary Erythrocyte-Derived miRNAs: Emerging Role in IgA Nephropathy.

Hematuria is one of the basic clinical manifestations of IgA nephropathy (IgAN). Isolated microscopic hematuria or microscopic hematuria combined with proteinuria is risk factor for the long-term prognosis of IgAN. Current evidence of the consequences of glomerular hematuria rests on insights from basic research on the molecular mechanisms of hemoglobin and related reactive oxygen species-induced tubular injury as well as on the clinical evidence of macroscopic hematuria-associated acute kidney injury (AKI) in IgAN. These researches may simply elucidate some effects of macroscopic hematuria but not microscopic hematuria. Recent studies conducted on blood and urinary erythrocytes have made progress. Researches have revealed that mature erythrocytes contain abundant, long, non-coding RNA, miRNA (microRNA) and Y RNA. Among the top 50 expressions of erythrocyte-derived miRNAs, 33 (66%) of them may be the potential urinary biomarkers of IgAN. Moreover, when urinary erythrocytes are compressed while exiting out of an impaired nephron, erythrocyte-derived vesicles (including microvesicles and apoptotic vesicles) may increase. Animal models for hematuria and human biopsy tissues confirm renal parenchymal cells could phagocytose red blood cells and erythrocyte-derived vesicles. These vesicles, which contain miRNAs, may alter the transcriptome of recipient cells and impact the occurrence and development of IgAN.

Giant single-molecule anisotropic magnetoresistance at room temperature.

We report an electrochemically assisted jump-to-contact scanning tunneling microscopy (STM) break junction approach to create reproducible and well-defined single-molecule spintronic junctions. The STM break junction is equipped with an external magnetic field either parallel or perpendicular to the electron transport direction. The conductance of Fe-terephthalic acid (TPA)-Fe single-molecule junctions is measured and a giant single-molecule tunneling anisotropic magnetoresistance (T-AMR) up to 53% is observed at room temperature. Theoretical calculations based on first-principles quantum simulations show that the observed AMR of Fe-TPA-Fe junctions originates from electronic coupling at the TPA-Fe interfaces modified by the magnetic orientation of the Fe electrodes with respect to the direction of current flow. The present study highlights new opportunities for obtaining detailed understanding of mechanisms of charge and spin transport in molecular junctions and the role of interfaces in determining the MR of single-molecule junctions.

Epidermal growth factor receptor inhibitor ameliorates excessive astrogliosis and improves the regeneration microenvironment and functional recovery in adult rats following spinal cord injury.

BACKGROUND: Astrogliosis is a common phenomenon after spinal cord injury (SCI). Although this process exerts positive effects on axonal regeneration, excessive astrogliosis imparts negative effects on neuronal repair and recovery. Epidermal growth factor receptor (EGFR) pathway is critical to the regulation of reactive astrogliosis, and therefore is a potential target of therapeutics to better control the response. In this report, we aim to investigate whether blocking EGFR signaling using an EGFR tyrosine kinase specific inhibitor can attenuate reactive astrogliosis and promote functional recovery after a traumatic SCI. METHOD: The astrocyte scratch injury model in vitro and the weight-drop SCI model in vivo were used as model systems. PD168393 was used to inhibit EGFR signaling activation. Astrocytic activation and phosphorylated EGFR (pEGFR) were observed after immunofluorescence staining and Western blot analysis. The rate of proliferation was determined by immunofluorescence detection of BrdU-incorporating cells located next to the wound. The levels of TNF-α, iNOS, COX-2 and IL-1ß in the culture medium under different conditions were assayed by ELISA. Western blot was performed to semi-quantify the expression of EGFR/pEGFR, glial fibrillary acid protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). Myelin was stained by Luxol Fast Blue Staining. Cresyl violet eosin staining was performed to analyze the lesion cavity volume and neuronal survival following injury. Finally, functional scoring and residual urine recording were performed to show the rats' recovery. RESULTS: EGFR phosphorylation was found to parallel astrocyte activation, and EGFR inhibitor PD168393 potently inhibited scratch-induced reactive astrogliosis and proinflammatory cytokine/mediator secretion of reactive astrocytes in vitro. Moreover, local administration of PD168393 in the injured area suppressed CSPGs production and glial scar formation, and resulted in reduced demyelination and neuronal loss, which correlated with remarkable hindlimb motor function and bladder improvement in SCI rats. CONCLUSIONS: The specific EGFR inhibitor PD168393 can ameliorate excessive reactive astrogliosis and facilitate a more favorable environment for axonal regeneration after SCI. As such, EGFR inhibitor may be a promising therapeutic intervention in CNS injury.

Concentrated sodium chloride catheter lock solution--a new effective alternative method for hemodialysis patients with high bleeding risk.

BACKGROUND: Locking catheter with heparin may increase bleeding risk of some hemodialysis (HD) patients. Hence, the security and effectivity of 10% concentrated sodium chloride (CSC) used as an alternative method for patients with high bleeding risk need to be investigated. METHODS: Seventy-two patients inserted temporary central venous catheters were divided into two groups randomly. A total of 3125 U/mL heparin saline (HS) was used in HS group and 10% CSC in CSC group to lock catheters. Heparin-free HD was used for the first time and plasma specimens were collected to test coagulation indicators before catheter-locking (at the end of HD) and at 30 min after it. Then, blood flow velocities (BFVs), incidences of catheter thrombosis, etc. were followed up at each time of HD. RESULTS: Activated partial thromboplastin time (APTT) of two groups had no difference at the end of heparin-free HD (27.100 [25.675-28.950] vs. 27.250 [25.150-29.575] second, p = 0.933), but at 30 minutes after using different catheter lock solutions, APTT of HS group was obviously longer than CSC group (50.100 [41.275-65.400] vs. 27.500 [25.525-29.875] second, p < 0.001). Catheters' retaining time of two groups were the same (p = 0.306), so did the average BFVs (p > 0.05). But catheters' thrombosis incidence and urokinase usage of HS group were less than CSC group (p < 0.05). CONCLUSION: Comparing with HS group, thrombosis incidences of CSC group increased, but catheters' retaining time and average BFVs remained the same and coagulation indicators of it were unaffected. Therefore, it can be an effective alternative lock method for HD patients with high bleeding risk.

[Effect of Ningdong Granule on the levels of IL-12 and TNF-alpha in children patients with Tourette's syndrome].

OBJECTIVE: To observe the effect of Ningdong Granule (NG) on serum levels of interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) of children patients with Tourette's syndrome (TS). METHODS: Totally 90 TS children patients were randomly assigned to the NG group, the NG + Tiapride group (abbreviated as the combined treatment group), and the Tiapride group, 30 in each group. Besides,another 30 healthy children were recruited as the healthy control group. Patients in the NG group were treated with NG (consisting of all gastrodia rhizome, Codonopsis pilosula, Ophiopogon japonicus, white peony root, Rhinocerotidae, oyster, earthworm, licorice root, etc.), one dose daily, administered by dissolving it in boiled water, taken in two portions in the morning and in the evening respectively. Patients in the Tiapride group took Tiapride Tablet, 50 -100 mg each time, twice daily. The dosage was adjusted according to individual difference and changes of pathogenic conditions. The maximal dosage was 300 mg per day. Those in the combined treatment group were treated with equal dose of NG and Tiapride Tablet in combination. The treatment course was 3 months for all. Changes of pathogenic condition before and after treatment were assessed by Yale global tic severity scale (YGTSS). Serum levels of IL-12 and TNF-alpha were detected by enzyme-labeled immunosorbent assay (ELISA) before and after treatment. RESULTS: (1) The total effective rate of the NG group, the combined treatment group, and the Tiapride group was 79.3%, 83.3%, and 67.9%, respectively. It was the lowest in the Tiapride group (P < 0.05). It was significantly higher in the combined treatment group than in the NG group (P < 0.05). (2) The post-treatment YGTSS score was obviously lower in each group after treatment than before treatment (P < 0.05). The posttreatment YGTSS score was obviously lower in the NG group and the combined treatment group than in the Tiapride group (P < 0.05), but with no statistical difference between the fromer two groups (P > 0.05).(3) Compared with the healthy control group before treatment, serum levels of IL-12 and TNF-alpha (pg/mL) were 124.95 +/- 22.78 and 209.52 +/- 21.69 in the NG group, 126.14 +/- 25.65 and 208.97 +/- 22.46 in the combined treatment group, 123.00 +/- 24.26 and 205.10 +/- 26.16 in the Tiapride group, being higher than those in the healthy control group (64.56 +/- 27.59 and 78.13 +/- 33.42; P < 0.05). After treatment, serum levels of of IL-12 and TNF-alpha were 104.67 +/- 16.84 and 183.01 +/- 24.95 in the NG group, 109.04 +/- 16.81 and 179.87 +/- 23.45 in the combined treatment group, significantly lower than before treatment (P < 0.05). But there was no statistical difference in serum levels of IL-12 or TNF-alpha in the Tiapride group between before treatment (123.00 +/- 24.26 and 205.10 +/- 26.16) and after treatment (117.75 +/- 16.79 and 199.76 +/- 33.21; P > 0.05). CONCLUSION: NG could modulate abnormal serum levels of IL-12 and TNF-alpha in TS children patients, which might be one of its pharmacodynamic mechanisms for treating TS.

Aspongopyrimidine A, a N-Peralkylated Histidine Zwitterion from Aspongopus chinensis against Alzheimer's Disease Targeting MAPRE3.

Aspongopyrimidine A (1), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2H-10λ4-imidazo[5,1-f]pyrrolo[2,1-b]pyrimidine motif, was isolated from the insect Aspongopus chinensis. The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N-atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.

Urinary miR-185-5p is a biomarker of renal tubulointerstitial fibrosis in IgA nephropathy.

Background: For IgA nephropathy (IgAN), tubular atrophy/interstitial fibrosis is the most important prognostic pathological indicator in the mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and presence of crescents (MEST-C) score. The identification of non-invasive biomarkers for tubular atrophy/interstitial fibrosis would aid clinical monitoring of IgAN progression and improve patient prognosis. Methods: The study included 188 patients with primary IgAN in separate confirmation and validation cohorts. The associations of miR-92a-3p, miR-425-5p, and miR-185-5p with renal histopathological lesions and prognosis were explored using Spearman correlation analysis and Kaplan-Meier survival curves. Bioinformatics analysis and dual luciferase experiments were used to identify hub genes for miR-185-5p. The fibrotic phenotypes of tubular epithelial cells were evaluated in vivo and in HK-2 cells. Results: miRNA sequencing and cohort validation revealed that the expression levels of miR-92a-3p, miR-425-5p, and miR-185-5p in urine were significantly increased among patients with IgAN; these levels could predict the extent of tubular atrophy/interstitial fibrosis in such patients. The combination of the three biomarkers resulted in an area under the receiver operating characteristic curve of 0.742. The renal prognosis was significantly worse in the miR-185-5p high expression group than in the low expression group (P=0.003). Renal tissue in situ hybridization, bioinformatics analysis, and dual luciferase experiments confirmed that miR-185-5p affects prognosis in patients with IgAN mainly by influencing expression of the target gene tight junction protein 1 (TJP1) in renal tubular epithelial cells. In vitro experiment revealed that an miR-185-5p mimic could reduce TJP1 expression in HK-2 cells, while increasing the levels of α-smooth muscle actin, fibronectin, collagen I, and collagen III; these changes promoted the transformation of renal tubular epithelial cells to a fibrotic phenotype. An miR-185-5p inhibitor can reverse the fibrotic phenotype in renal tubular epithelial cells. In a unilateral ureteral obstruction model, the inhibition of miR-185-5p expression alleviated tubular atrophy/interstitial fibrosis. Conclusion: Urinary miR-185-5p, a non-invasive biomarker of tubular atrophy/interstitial fibrosis in IgAN, may promote the transformation of renal tubular epithelial cells to a fibrotic phenotype via TJP1.

[Effect of ningdong granule on stereotyped behaviors in Tourette syndrome model rats of different Chinese medical syndromes].

OBJECTIVE: To observe the effect of Ningdong Granule (NDG) on stereotyped behaviors in Tourette's syndrome (TS) model rats of different Chinese medical syndromes. METHODS: Thirty-two Wistar rats were used to establish TS models of different Chinese medical syndromes (n =8) induced by TS children patients' sera of 4 syndromes, i.e., Xin-Gan deficiency syndrome (XGDS), Gan-Shen yin deficiency syndrome (GSYDS), sputum-turbid blocking aperture syndrome (STBAS), and Gan hyperactivity Pi deficiency syndrome (GHPDS). Corresponding sera was micro-infused to them while administering NDG (120 mg/kg each time, thrice daily, for 3 successive weeks). Besides, another normal control group (n =8) was set up by injecting sera from healthy children plus intragastric perfusion of normal saline. Stereotyped behaviors were recorded on the 1st, 7th, 14th, and 21st day after administration of NDG. RESULTS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy control [(1.28 +/- 0.36) UL vs. (0.52 +/- 0.24) U/L, P < 0.01 ]. It was (1.34 +/- 0.41) U/L in the XGDS group, (1.19 +/- 0.51) U/L in the GSYDS group, (1.29 +/- 0.61) U/L in the STBAS group, and (1. 17 +/- 0.45) U/L in the GHPDS group, showing no statistical difference (P > 0.05). There was no statistical difference in stereotypic behaviors of rats after treatment among the four different Chinese medical syndromes (P > 0.05). At day 7, 14, and 21 after treatment by NDG, the times of stereotyped behaviors were significantly less in the XGDS group than in the other three groups at the same time points except in the GHPDS group at day 14 (P < 0.05, P < 0.01). Meanwhile, the total numbers of stereotyped behaviors in the XGDS group [(42.8 +/- 12.6)] was obviously superior to that in the GSYDS group [(29.3 +/- 13.7)], the STBAS group [(21.9 +/- 10.4)], and the GHPDS group [(30.6 +/- 9.6)], showing statistical difference (P < 0.01, P < 0.05) after treatment by NDG at day 21. CONCLUSIONS: The anti-neural antibody serum concentration in TS children was significantly higher than that in healthy children. Stereotyped behaviors could be induced in rats after intrastriatal micro-infusion of TS sera rich in anti-neural antibody. TS model rats of XGDS were better improved than rats in the other 3 groups after treatment by NDG.

COX-2 and iNOS inhibitory abietane diterpenoids from Pinus yunnanensis exudates.

Pinuskesiols A-F (1-6), six new structurally diverse abietane diterpenoids were isolated from Pinus yunnanensis resins. Their structures including absolute configurations were characterized by using spectroscopic and computational methods. All the compounds bear a carbonyl functionality at C-4 with 1 and 2 behaving as a lactone thereof. The isopropyl group is attached to C-13 via O-atom in 3. In addition, the presence of a Δ5(6) double bond and a ketone at C-7 makes 2 a large conjugated system. Biological evaluation revealed that 1, 2, and 4 could concentration-dependently inhibit iNOS and COX-2 expression in lipopolysaccharide-induced RAW 264.7 cells with 2 to be the most active toward COX-2 inhibition.

Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae.

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.

Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

The Efficacy of Acupuncture on Tic Disorders in Children: A Retrospective and Propensity Score-Matched Study.

Background : Acupuncture has been considered as a complementary or alternative therapy for children with tic disorders (TD), but its efficacy remains largely unknown. This study retrospectively examined the efficacy of acupuncture treatment for TD in children over the course of 12 weeks. Methods: Data were collected from Traditional Chinese Medicine clinics in a public pediatric hospital in Shanghai between June 2020 and March 2021. A total of 250 patients with TD were included in the study, with 122 patients exposed to acupuncture therapy combined with conventional treatment (observation group), and 128 patients exposed to conventional treatment alone (control group). Propensity score matching analyses were used to balance baseline characteristics, resulting in 78 matched patients for each group. Reductions in the Yale Global Tic Severity Scale (YGTSS) total score were analyzed in the two groups after 12 weeks of treatment. Results: The two groups reached equilibrium in terms of baseline demographic characteristics and YGTSS total score after the propensity score matching (P > 0.05). Compared to the control group, the reduction in the YGTSS total score after 12 weeks of treatment was greater for the observation group (OR = 2.94, 95% CI: 1.03, 8.39, P = 0.04), and this association was stronger for patients who had significant vocal tics (ß = 0.29, 95% CI: 0.88, 2.68, P = 0.001). The clinical efficacy for the observation group was significantly better than the control group. Conclusions: We provided preliminary evidence supporting the therapeutic effect of acupuncture for TD in children. Hence, our findings indicate that acupuncture could be an adjuvant treatment efficacious for TD in children, especially for vocal tics.

[Epidemiology of anticoagulation for hemodialysis patients: survey of 842 cases in seven hemodialysis centers].

OBJECTIVE: To investigate the anticoagulant methods and characters of hemodialysis patients in hospitals of Grade III Level A. METHODS: A questionnaire survey was conducted in 7 hemodialysis centers of class 3 first level general hospital in Beijing, Shenyang, Harbin, and Dalian, on the hemodialysis status, primary diseases, anticoagulation methods, and complications. RESULTS: 808 of the 842 patients (95.9%) underwent hemodialysis, and 34 patients (4.1%) were subjected to hemodialysis filtration. 606 hemodialysis patients (74.9%) used heparin as the anticoagulant, and the doses and using method were different among different centers. 223 patients (26.5%) used low molecular weight heparin (LMWH) with different kinds, doses and using methods. The underlying diseases included diabetes (15.1%), hypertension (9.4%), and other diseases (75.5%). There was no significant difference in the dosage of heparin among different diseases, while the dosage of LMWH was lower for the diabetes and hypertension patients. 171 patients (20.3%) had hemorrhagic tendency, and 67 patients (20.3%) suffered from thrombus. The dosage of heparin was lower in the patients with hemorrhagic tendency while no difference was found in the dosages of LMWH among the patients with different diseases. Antiplatelet agents were co-administrated in 172 hemodialysis patients (20.4%). The percentages of co-administration of antiplatelet for patients with thrombus and hemorrhagic tendency were 14% and 12.8% respectively. The dosages of heparin and LMWH were higher in the patients with co-administration than those without co-administration. Coagulation marker examination was conducted in only 385 patients (45.7%), and no difference in the frequency of coagulation marker examination was found among the patients with hemorrhagic tendency, thrombus, and other diseases. CONCLUSION: Heparin is the main anticoagulant in hemodialysis. The anticoagulant methodology in hemodialysis is still empirical without clotting monitor and standard for usage of anticoagulants.

Comprehensive Analysis of DNA Methylation and Gene Expression Datasets Identified MMP9 and TWIST1 as Important Pathogenic Genes of Lung Adenocarcinoma.

Due to the high mortality of lung cancer, early diagnosis followed by early effective treatment is the key to prognosis improvement, which demands to identify the biological targets. Therefore, a multistage screening analysis was used to identify biological targets of lung adenocarcinoma. Two independent datasets of DNA methylation and RNA expression microarray in lung adenocarcinoma and normal lung tissues were chosen from the Gene Expression Omnibus. The association between DNA methylation and gene expression was explored, and the prognostic value of the hub genes was also evaluated. In this study, 8533 differential methylation sites, mostly located in the CpG island region and corresponding to 2754 genes (referred as differential methylation genes), were detected from methylation microarray. Besides, we obtained 830 differential expression genes, including 570 downregulated and 260 upregulated genes, through differential expression analysis. Protein-protein interaction analysis identified CXCL12, GFR, KDR, MMP9, TEK, and TWIST as core nodes, involving in the process of tumor cell identification, cell growth, cytokine secretion, inflammatory response, and angiogenesis. Among them, MMP9 and TWIST1 were identified as more valuable biological targets for the early diagnosis and targeted therapy of lung cancer through Kaplan-Meier analysis of TCGA lung adenocarcinoma datasets. Our study should contribute to the diagnosis and treatment of lung adenocarcinoma.

U6 can be used as a housekeeping gene for urinary sediment miRNA studies of IgA nephropathy.

Recent studies have indicated that urinary sediment miRNAs not only are able to serve as non-invasive diagnostic biomarkers for IgA nephropathy (IgAN) but may also be closely related to several clinical and pathological indicators. However, the lack of a suitable internal reference miRNA has hampered research into urinary sediment miRNAs. To date, U6 has been used as a reference gene in urinary sediment miRNA studies mostly based on the results from studies using tissue samples and cell lines. In a total of 330 IgAN patients, 164 disease control patients and 130 normal control patients, there was no significant difference in U6 levels. We also compared the U6 levels in different types of primary glomerular disease groups (IgA nephropathy, membranous nephropathy, minimal change nephrosis and focal segmental glomerular sclerosis). The results confirmed that there was no significant difference in the expression of U6 in different primary glomerular disease groups. Moreover, treatment had no significant effect on the expression levels of U6 in IgA nephropathy. Therefore, U6 is an excellent housekeeping gene for urinary sediment miRNA studies of IgA nephropathy.

Impact of aging on the risk of platinum-related renal toxicity: A systematic review and meta-analysis.

BACKGROUND: Renal toxicity limits the clinical use of platinum-based therapy in the elderly. In order to clarify the impact of aging on the risk of platinum-related nephrotoxicity, the following meta-analysis was performed. METHODS: We searched multiple databases for studies published before January 2017. The inclusion criteria were case-control, cohort studies published in any language. RESULTS: The risk of platinum-induced nephrotoxicity in the older group was 1.43 times (risk rate) higher than in the non-older group. Platinum-induced nephrotoxicity in older patients was mainly I/II. There was no significant difference in the incidence of grade III/IV renal toxicity between groups. The risk for elderly patients in Asia was significantly higher than in Europe and North America. Carboplatin had a lower risk of renal toxicity and only half of the amount of moderate and severe nephrotoxicity than cisplatin. In the age stratification analysis, the RR values were 1.43, 1.51 and 1.35 respectively for the elderly group (55, 60, 70 years old), and all had significant differences. The risk of platinum-related nephrotoxicity in elderly patients was significantly increased in the high comorbidity rate group. Moreover, the RR values of the normal renal function group were significantly higher than that of the 'no mention or renal insufficiency' subgroup. CONCLUSIONS: Aging increased the risk of platinum-induced nephrotoxicity by 43%, partly due to more comorbidities in elderly patients, and mild renal toxicity was dominant. The risk of renal toxicity of the elderly patients in Asian countries was much higher than that of in European countries and North America.