Thermodynamic Simulation Calculations of Phase Transformations in Low-Aluminum Zn-Al-Mg Coatings.

This study delves into the formation, transformation, and impact on coating performance of MgZn2 and Mg2Zn11 phases in low-aluminum Zn-Al-Mg alloy coatings, combining thermodynamic simulation calculations with experimental verification methods. A thermodynamic database for the Zn-Al-Mg ternary system was established using the CALPHAD method, and this alloy's non-equilibrium solidification process was simulated using the Scheil model to predict phase compositions under varying cooling rates and coating thicknesses. The simulation results suggest that the Mg2Zn11 phase might predominate in coatings under simulated production-line conditions. However, experimental results characterized using XRD phase analysis show that the MgZn2 phase is the main phase existing in actual coatings, highlighting the complexity of the non-equilibrium solidification process and the decisive effect of experimental conditions on the final phase composition. Further experiments confirmed that cooling rate and coating thickness significantly influence phase composition, with faster cooling and thinner coatings favoring the formation of the metastable phase MgZn2.

A comprehensive LC-MS/MS method for simultaneous analysis of 65 synthetic cannabinoids in human hair samples and application to forensic investigations.

Synthetic cannabinoids (SCs) represent a diverse class of new psychoactive substances characterized by extensive substance variety and severe abuse implications. The current situation of synthetic cannabinoid abuse in China is getting worse, with an increasing number of SC variants emerging. Therefore, it is imperative to improve synthetic cannabinoid detecting methods to align with the prevalent abuse situation in the region. In this study, a reliable and validated liquid chromatography-tandem mass spectrometry method was developed for the qualitative and quantitative analysis of 65 SC analogues in human hair samples. The validation results demonstrated satisfactory linearity (r ≥ 0.99) within the range of 25-2500 pg/mg for each SC analogue. The method exhibited limits of detection ranging from 10 to 15 pg/mg and limits of quantification ranging from 25 to 40 pg/mg. The relative standard deviations of intra-day precision and inter-day precision were below 15 %. Furthermore, negligible matrix effects were observed, with recovery rates ranging from 85.70 % to 119.43 %. Analysis of abuser demographics revealed that the primary group engaged in SC analogue abuse consisted of adolescents, predominantly males, accounting for 79.5 % of cases. Among the suspected individuals, ADB-BUTINACA and MDMB-4en-PINACA were the most frequently detected substances. The present study develops a highly sensitive analytical method and provides a comprehensive overview of the prevalence of SC abuse in the eastern region of China.

The Mitochondrial-Derived Peptide (MOTS-c) Interacted with Nrf2 to Defend the Antioxidant System to Protect Dopaminergic Neurons Against Rotenone Exposure.

MOTS-c is a 16-amino acid mitochondrial-derived peptide reported to be involved in regulating energy metabolism. However, few studies have reported the role of MOTS-c on neuron degeneration. In this study, it was aimed to explore the action of MOTS-c in rotenone-induced dopaminergic neurotoxicity. In an in vitro study, it was observed that rotenone could influence the expression and localization of MOTS-c significantly in PC12 cells, with more MOTS-c translocating into the nucleus from mitochondria. Further study showed that the translocation of MOTS-c from the mitochondria into the nucleus could directly interact with Nrf2 to regulate HO-1 and NQO1 expression in PC12 cells exposed to rotenone, which had been suggested to be involved in the antioxidant defense system. In vivo and in vitro experiments demonstrated that exogenous MOTS-c pretreatment could protect PC12 cells and rats from mitochondrial dysfunction and oxidative stress induced by rotenone. Moreover, MOTS-c pretreatment significantly decreased the loss of TH, PSD95, and SYP protein expression in the striatum of rats exposed to rotenone. In addition, MOTS-c pretreatment could clearly alleviate the downregulated expression of Nrf2, HO-1, and NQO1, as well as the upregulated Keap1 protein expression in the striatum of rotenone-treated rats. Taken together, these findings suggested that MOTS-c could directly interact with Nrf2 to activate the Nrf2/HO-1/NQO1 signal pathway to defend the antioxidant system to prevent dopaminergic neurons from rotenone-induced oxidative stress and neurotoxicity in vitro and in vivo.

Shrink polymer based electrochemical sensor for point-of-care detection of prostate-specific antigen.

There is a growing but unmet need for point-of-care detection of prostate-specific antigen (PSA) in body fluid which may facilitate early diagnosis and therapy of prostate cancer in a cost-effective and user-friendly way. Low sensitivity and narrow detection range limits applications of point-of-care testing in practice. Here, an immunosensor is first presented based on shrink polymer and integrated into a miniaturized electrochemical platform for detecting PSA in clinical samples. The sensing electrode was prepared by sputtering a gold film on shrink polymer, followed by heating to shrink the electrode to a small size with wrinkles from nano-scale to micro-scale. These wrinkles can be directly regulated by the thickness of the gold film with high specific areas for enhancement of antigen-antibody binding (3.9 times). A distinct difference between electrochemical active surface area (EASA) and response to PSA of shrink electrodes was observed and discussed. The electrode was treated with air plasma and modified with self-assembled graphene to further enhance the sensor's sensitivity (10.4 times). The shrink sensor with gold 200 nm thick integrated into the portable system was validated by a label-free immunoassay for detection of PSA in 20 µL serum within 35 mins. It exhibited a limit of detection of 0.38 fg/mL, the lowest among label-free PSA sensors, and a wide linear response from 10 fg/mL to 1000 ng/mL. Moreover, the sensor demonstrated reliable assay results in clinical serums, comparable to the commercial chemiluminescence instrument, confirming its feasibility for clinical diagnosis.

[The Screening Approaches for 34 Common Drugs and Metabolites in Biological Samples by Liquid Chromatography Orbital Trap Mass Spectrometry].

Objective: To establish a high-performance liquid chromatography orbital trap mass spectrometry (HPLC-Obitrap MS) method for screening 34 common drugs and metabolites in biological samples. Methods: The target analytes in urine and blood samples were extracted with ethyl acetate, concentrated by nitrogen blowing and redissolved. The hair samples were washed with water and acetone, dried and cut into bits of about 1 mm, and then crushed in a freezing grinder. The analytes were extracted with methanol, and after filtration, the filtrate was used for instrumental analysis. Hypersil Gold PFP (2.1 mm×100 mm, 3 µm) column was used for chromatographic separation. Methanol and 5 mmol/L ammonium acetate solution were used as mobile phase with gradient elution at a flow rate of 400 µL/min. Mass spectrometry was done by electrospray positive and negative ion alternation mode. The data were collected using Full MS and Full MS/dd-MS2 mode. Xcalibur 4.0 software was used to control instruments and to collect data, and TraceFinder 3.3 was used for screening and identification. Results: The method's detection limits for 34 drugs and their metabolites in blood, urine and hair samples were 3.30-10700 ng/L, 4.43-5440 ng/L, 0.0350-4.21 µg/kg, respectively. The intra-day and inter-day precisions of the spiked samples at the levels of 5.0, 10, and 20 µg/L were 3.50%-6.00% and 4.18%-9.90%, respectively. A total of 1125 biological samples of urine, blood and hair were collected and screened. The results showed that 96.7% of the drug users were taking a single drug, while 3.3% were mixed drug users. The main types of drug of abuse were methamphetamine (75.8%), heroin (18.5%), ketamine (2.4%) and other drugs (3.3%), and 87.9% of the positive samples were from male users. Compared with the results of high-performance liquid chromatography triple quadrupole mass spectrometry, this method can be used to identify more types of drugs in one run and to conduct retrospective analysis. Conclusion: The method established in the study is simple and sensitive and is well suited for the screening of common drugs and metabolites in biological samples.

Transcriptomic investigation of the effects of TDCPP on PC12 and GC2 cells with experimental validation.

TDCPP is a flame retardant which has nervous and reproductive toxicity. Although there is a close association between nervous and reproductive system, the exact toxic mechanism of TDCPP in these systems is still seldom, especially in a genome scale. In this study, we explored the transcriptomic landscape of TDCPP in PC12 and GC2 cells using RNAseq method. A total of 465 co-differential expressed genes were found. These genes were mainly enriched in extra-cellular matrix, cell adhesion, cell cycle arrest, oxidoreductase activity GO terms, and PI3K/AKT, focal adhesion, ECM-receptor interaction KEGG pathways. Hub genes (ANXA1, COL27A1, GAS6, GNB4 and THBS1) were extracted using STRING and confirmed by qPCR experiment. Vimentin, HSPA5 and Caspase3 were proved to be responsible to TDCPP in GC2 and PC12 cells. Knockdown assay in PC12 cells showed that these hub genes could also affect the protein expression of vimentin, HSPA5 and Caspase3. In summary, TDCPP might exert its toxic effect through disturbing focal adhesion, ECM-receptor interaction and PI3K/Akt pathways. One of the mechanisms could be influence on the cytoskeleton (vimentin), ER stress (HSPA5) and apoptosis (Caspase3). The sequence data in this study might be a useful resource for future TDCPP related researches.

Identification of Prognostic Biomarkers Associated with Cancer Stem Cell Features in Prostate Adenocarcinoma.

BACKGROUND Prostate adenocarcinoma (PRAD) is the second most common malignancy in males and the fifth leading cause of cancer mortality. Cancer stem cells (CSCs) play an important role in the occurrence and development of PRAD, however, the prognostic biomarkers associated with CSC features have not been identified in PRAD. MATERIAL AND METHODS In order to identify the prognostic stemness-related genes (SRGs) of PRAD, the RNA sequencing data of patients with PRAD were retrieved from The Cancer Genome Atlas (TCGA) databases. The mRNA expression-based stemness index (mRNAsi) and the differential expressed genes (DEGs) were evaluated and identified. The associations between the mRNAsi and tumorigenesis, overall survival (OS), prostate-specific antigen (PSA) value, and Gleason score were also established by nonparametric test and Kaplan-Meier survival analysis. The SRGs were identified as the overlapped DEGs of PRAD-associated DEGs and the mRNAsi-associated DEGs. Based on the prognostic SRGs, the predict model was constructed. Its accuracy was tested by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve and the risk score. RESULTS A total of 6005 PRAD-associated DEGs and 2462 mRNAsi-associated DEGs were identified. The mRNAsi was significantly upregulated in PRAD and associated with the PSA value and Gleason score. A total of 1631 SRGs were identified, with 36 prognostic SRGs screened by the univariate Cox analysis. Based on the prognostic SRGs, the predict model was constructed with the AUC of 0.986. Moreover, the risk score of the model was proved to be an independent prognostic factor, indicating its significant applicability. CONCLUSIONS Our data demonstrate the mRNAsi as a reliable index for the tumorigenesis, PSA value, and Gleason score of PRAD. Additionally, this study provides a well-applied model for predicting the OS for patients with PRAD based on prognostic SRGs.

Potassium Iodide Potentiates Bacterial Killing by Helium Atmospheric Pressure Plasma Jet.

Cold atmospheric plasma (CAP) is an effective new antimicrobial approach that is gaining increasing attention and has a wide range of potential applications in biomedical fields. Among all of the bactericidal factors generated by CAP, the synergy of reactive nitrogen species (RNS) and reactive oxygen species is generally considered as the main reason for its high bactericidal efficiency. However, the produced RNS (such as nitrite) may also pose potential risks to human health. Therefore, it is of significance to keep the high disinfection efficiency of CAP but with producing no or little harmful RNS. In this study, we investigated whether it is possible to improve the disinfection efficiency of CAP without producing the harmful RNS by adding a certain amount of inert halogen salt such as potassium iodide (KI). We found that the inactivation of both Gram-negative and Gram-positive bacteria by helium atmospheric pressure plasma jet (He-APPJ), one form of CAP, is enhanced consistently in the presence of a certain amount of KI. The mechanism of action is due to the fact that the He-APPJ-generated hydrogen peroxide (H2O2) oxidizes the iodide anion to triiodide (I3 -), which contributes to the major bactericidal activity. We believe that the results in this work can be highly relevant to the practical application of plasma for disinfection in the biomedical field.

MicroRNA-761 inhibits the metastasis of gastric cancer by negatively regulating Ras and Rab interactor 1.

Gastric cancer (GC), the second most common malignant cancer worldwide, gives rise to a number of cancer-associated fatalities annually. Accumulating evidence has shown that microRNAs (miRs) may serve as oncogenes or tumor suppressors in GC development. The aim of this study was to discover the expression, function and mechanism of miR-761 in GC progression. First, the findings revealed that the expression level of miR-761 was significantly decreased in GC cell lines and tissues. The functional studies showed that miR-761 in GC cells inhibited tumor proliferation and metastasis. In the mechanistic study, through an online database search and luciferase assay, Ras and Rab interactor 1 (RIN1), which has been demonstrated as an oncogene in various types of cancer, including GC, was identified as a target of miR-761. Notably, miR-761 expression was demonstrated to be negatively correlated with RIN1 mRNA levels in GC tissues. Simultaneously, overexpression of RIN1 partially rescued the inhibitory effect of miR-761 mimic in the GC cells. The present study provided new insights into the role of miR-761 in the progression of GC, and implicated the potential application of miR-761 in GC cell therapy.

Desumoylation of aggrecan and collagen II facilitates degradation via aggrecanases in IL-1ß-mediated osteoarthritis.

Background: Aggrecan plays a crucial role in the ability of tissues to withstand compressive loads during the pathological progression of osteoarthritis (OA). Progressive loss of aggrecan from cartilage may result in exposure of the collagen matrix and can lead to its disintegration by metalloproteases. Although aggrecanases are expressed constitutively in human chondrocytes, the degradation of aggrecan is induced by proinflammatory cytokines; however, little is known about the underlying mechanisms. Methods: Human primary chondrocytes from OA patients or healthy donors and human chondrogenic SW1353 cells were cultured and stimulated with IL-1ß in vitro, the mRNA expressions and protein levels of MMP-13, ADAMTS-4, ADAMTS-5, SENP1, and SENP2 were determined using real time PCR and Western blot, respectively. The localizations of aggrecan and Col-II, as well as the SUMOylation modification of these proteins were analyzed using immunofluorescence and immunoprecipitation assays, respectively. Results: Our results showed that a proinflammatory cytokine interleukin-1ß induced the OA model and desumoylation of aggrecan and collagen type II because the small ubiquitin-like modifier 2/3 (SUMO2/3) was co-localized with aggrecan and collagen type II proteins and interacted physically with them. Mechanistic studies have shown that knockdown of SUMO2/3 expression can significantly enhance the rate of degradation of aggrecan and collagen type II at both the mRNA and protein levels in the OA model. In addition, SUMO-specific protease 2 (SENP2) plays important roles in the desumoylation of aggrecan, while knockdown of SENP2 can protect aggrecan and collagen type II. Clinical assays have shown that OA patients have higher SENP2 levels than healthy controls, and the SENP2 level correlates negatively with both aggrecan and collagen type II levels. Conclusion: SENP2 desumoylates aggrecan and collagen type II proteins in the inflammation induced OA, and SENP2 expression correlates with OA progression.

Associations of hyperuricemia, gout, and UA-lowering therapy with the risk of fractures: A meta-analysis of observational studies.

OBJECTIVE: A systematic review and meta-analysis were conducted to investigate the associations of hyperuricemia, gout, and uric acid (UA)-lowering therapy with the risk of fractures. METHODS: Electronic searches on PubMed, the Cochrane Library, and Embase were conducted from inception to January 2, 2019. Observational studies assessing the effects of hyperuricemia, gout, and UA-lowering therapy on fractures were included in the meta-analysis. Summary risk estimates with 95% confidence intervals (CI) were calculated by a random-effects model. RESULTS: A total of 14 eligible studies with 909 803 participants and 64 047 incident fractures were included. The results suggested that hyperuricemia and gout are not associated with any type of fracture (relative risk [RR], 0.98, 95% CI 0.85-1.11; P = 0.71) or osteoporotic fractures (RR, 1.02, 95% CI 0.90-1.14; P = 0.79). Further analysis indicated that hyperuricemia is associated with a lower risk of fractures (RR, 0.80, 95% CI 0.66-0.96; P = 0.02) but not with osteoporotic fractures (RR, 0.84, 95% CI 0.68-1.03; P = 0.10). However, gout is associated with an increased risk of fractures (RR, 1.17, 95% CI 1.04-1.31; P = 0.007) as well as osteoporotic fractures (RR, 1.13, 95% CI 1.00-1.26; P = 0.045). Furthermore, no significant association of UA-lowering therapy with the risk of fractures was found compared with the placebo (RR, 0.88, 95% CI 0.76-1.03; P = 0.11). Evidence supporting a non-linear association between serum UA levels and fractures was found (P < 0.001 for non-linearity), which revealed a U-shaped curve. CONCLUSION: Our meta-analysis revealed that hyperuricemia was associated with lower risk for any type fracture but not associated with osteoporotic fractures; however, gout was associated with an increased risk of any type fracture as well as osteoporotic fractures. Notably, a U-shaped relationship may exist between the serum UA level and fractures. The associations observed in our study may be due to reasons other than causality.

Improved production of polysaccharides in Ganoderma lingzhi mycelia by plasma mutagenesis and rapid screening of mutated strains through infrared spectroscopy.

As a traditional Chinese medicine, Ganoderma lingzhi has attracted increasing attention for both scientific research and medical application. In this work, in order to improve the production of polysaccharides from an original wide-type (WT) strain (named "RWY-0") of Ganoderma lingzhi, we applied atmospheric-pressure dielectric barrier discharge (DBD) nonthermal plasma to the protoplasts of RWY-0 for mutagenesis treatment. Through a randomly amplified polymorphic DNA (RAPD) assay, at least 10 mutagenic strains were confirmed. They also showed different mycelium characteristics in terms of shape, color, size and biomass in liquid fermentation. The mutant strains were examined by infrared spectroscopy, and based on the established near-infrared (NIR) quantification model, the polysaccharide contents in these mutants were quantitatively evaluated. As a result, we found that the Ganoderma polysaccharide contents in some of the mutant strains were significantly changed compared with that of the original WT strain. The polysaccharide content of RWY-1 G. lingzhi was considerably higher than that of the WT strain, with an increase of 25.6%. Thus, this preliminary work demonstrates the extension of the plasma mutagenesis application in acquiring polysaccharide-enhanced Ganoderma lingzhi mutants and shows the usefulness of NIR spectroscopy in the rapid screening of mutagenic strains for other important ingredients.

Degradation of norfloxacin in aqueous solution by atmospheric-pressure non-thermal plasma: Mechanism and degradation pathways.

Norfloxacin is a synthetic antibiotics drug which is widely used in the treatment of infectious diseases and also often carelessly released into natural environment resulting in antibiotics-contaminated wastewater. In this work, we employed atmospheric-pressure non-thermal dielectric barrier discharge (DBD) to treat norfloxacin-contaminated water and investigated the degradation efficiency and mechanism for the plasma treatments under different conditions with varied working gas atmospheres. Our results showed that the DBD efficiency for norfloxacin degradation depended on reactive oxygen/nitrogen species (RONS) produced in the plasma treatment, while the plasma-induced hydroxyl radical played a critical role in the norfloxacin degradation. For O2-DBD, except for the contribution from reactive oxygen species (ROS), ozone could also play an important role. For N2-DBD, reactive nitrogen species (RNS) could work synergistically with H2O2 to enhance the degradation effect. We also checked the plasma activated liquid (PAL) effect and analyzed the degradation products so that the degradation mechanism and pathways could be elucidated. This work may therefore provide the guidance for effective and feasible application of low-temperature plasma technology in treatment of antibiotics-contaminated wastewater.

Degradation of 2, 4-dichlorophenol in aqueous solution by dielectric barrier discharge: Effects of plasma-working gases, degradation pathways and toxicity assessment.

Chlorinated phenols are a class of contaminants found in water and have been regarded as a great potential risk to environment and human health. It is thus urgent to develop effective techniques to remove chlorinated phenols in wastewater. For this purpose, we employed dielectric barrier discharge (DBD) in this work and studied the efficiency of DBD for the degradation of 2,4-dichlorophenol (2,4-DCP), one of the most typical chlorophenols in the environment. The effects of pH value, applied voltage and plasma-working gases on the dichlorophenol-removal efficiency were investigated. The results demonstrate that DBD plasma could successfully degrade 2,4-DCP, achieving efficiency of 98.16% (k = 1.09 min-1) in the Ar-DBD system, and 77.60% (k = 0.48 min-1) in the N2-DBD system, with the process following the first-order kinetics. The removal efficiency was reduced in the presence of radical scavengers, confirming that hydroxyl radicals played a key role in the degradation process, while other active substances were also found such as nitrogen radicals in the N2-DBD system, which was found to have also contribution to the degradation of 2,4-DCP. The intermediates and final products generated in the degradation process were analyzed using gas chromatography-mass spectrometry (GC-MS). Based on the identification of intermediates, the degradation pathways and mechanism were proposed and discussed. Besides, the toxicity of the DBD treated 2,4-DCP solution was also assessed using GFP-expressing recombinant Escherichia coli (E. coli) as the testing organism, showing that plasma treatment could substantially reduce the toxic effect of 2,4-DCP.

miR-24-3p stimulates migration, invasion and proliferation of prostate cancer cells by targeting suppressor of cytokine signaling 6.

Prostate cancer is among the most widespread malignancies affecting men in the world. Its aggressive evolution has been associated with altered expression of suppressor of cytokine signaling 6 (SOCS6) but very little is known about the mechanism by which this alteration occurs. The purpose of this study was to explore the role of SOCS6 in prostate cancer cells and the involvement of its regulating microRNA (miR), miR-24-3p. Prostate cancer cell lines were used to determine the transcription level of miR-24-3p and SOCS6 by quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and Western blot. Cell proliferation and cell migration assays were doneto determine the effect of miR-24-3p mimics and inhibitors on cell proliferation, invasion and migration. Luciferase reporter assay with SOCS6 3'-UTR was performed to confirm the control of SOCS6 expression by the miR. The results showed that miR-24-3p was up-regulated in prostate cancer cells whereas SOCS6 protein was downregulated. Overexpression of miR-24-3p in prostate cancer cells promoted cell proliferation, inhibited apoptosis, and increased cell migration and invasion. Luciferase reporter assays showed that SOCS6 is a direct target of its negative regulator miR-24-3p and overexpression of SOCS6 reverses the effects of miR-24-3p on the metastatic phenotype of prostate cancer cells. These results show case miR-24-3p up-regulation in prostate cancer and a mechanism for inhibition of SOCS6 expression. Thus, the miR-24-3p/SOCS6 pathway could be a relevant avenue for prostate cancer treatment.

Prognostic analysis of Chinese patients with metastasis renal cell cancer receiving sorafenib: results from a multicenter long-term follow-up retrospective study.

The effects of sorafenib for Chinese patients with metastatic renal cell cancer (mRCC) were evaluated to figure out the relationship between clinical variables and prognosis. The data were analyzed retrospectively from six comprehensive cancer centers in Northeast China. All cases were diagnosed as mRCC histopathologically without exception. Patients were taken 400 mg sorafenib orally twice daily until progression of disease or intolerable toxic reaction occurred. Overall survival (OS), progression-free survival (PFS), and the influence of clinical variables on survival were appointed as main outcome measures. Clinical data were analyzed using SPSS statistical software. P<0.05 was considered as statistically significant. A total of 131 patients were available for survival analysis. The median follow-up periods were 16.9 months, and the median OS and PFS were 16.1 months and 10.5 months, respectively. Univariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), metastatic sites, and previous therapy were significantly associated with OS, whereas PFS was merely associated with ECOG PS and previous therapy. The multivariate analysis suggested that ECOG PS, metastatic sites, and previous therapy were the independent prognostic factors for OS, and ECOG PS and previous therapy as the independent prognostic factors for PFS. In the subgroup analysis for patients with visceral metastasis, the prognosis of patients with lung metastasis alone was better than those cases with liver metastasis alone or multiple organs metastasis. In our study, sorafenib shows a higher curative activity for patients with mRCC in Northeast China. ECOG PS, metastatic lesions, and previous therapy may be important parameters for OS and PFS prediction. Lung metastases alone may be a more sensitive indicator for sorafenib than other organ metastases.

Nomogram predicting renal insufficiency after nephroureterectomy for upper tract urothelial carcinoma in the Chinese population: exclusion of ineligible candidates for adjuvant chemotherapy.

OBJECTIVES: To report the decline of renal function after radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC) patients and to develop a nomogram to predict ineligibility for cisplatin-based adjuvant chemotherapy (AC). METHODS: We retrospectively analyzed 606 consecutive Chinese UTUC patients treated by RNU from 2000 to 2010. We chose an eGFR of 60 and 45 ml/min/1.73 m(2) as cut-offs for full-dose and reduced-dose AC eligibility. RESULTS: Median eGFR for all patients before and after surgery was 64 and 49 ml/min/1.73 m(2) (P < 0.001). The proportion of patients ineligible to receive full-dose and reduced-dose AC changed from 42% to 74% and from 20% to 38.1%. Older age (OR = 1.007), preoperative eGFR (OR = 0.993), absence of hydronephrosis (OR = 0.801), smaller tumor size (OR = 0.962), and tumor without multifocality (OR = 0.876) were predictive for ineligibility for full-dose AC. Preoperative eGFR (OR = 0.991), absence of hydronephrosis (OR = 0.881), tumor located in renal pelvis (OR = 1.164), and smaller tumor size (OR = 0.969) could predict ineligibility for reduced-dose AC. The c-index of the two models was 0.757 and 0.836. Postoperative renal function was not associated with worse survival. CONCLUSIONS: Older age, lower preoperative eGFR, smaller tumor size, tumor located in renal pelvis, and absence of hydronephrosis or multifocality were predictors of postoperative renal insufficiency.

[Five-year therapeutic experience of sorafenib for patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the tolerability and safety of sorafenib for patients with advanced renal cell carcinoma. METHODS: Among 63 cases of advanced renal cell carcinoma, there were 45 males and 18 females with a median age of 57 years. And 48 patients had recurrence or metastasis after nephrectomy. And cytokine therapy was offered for 36 of them before recurrence or metastasis. Postoperative recurrence or metastasis occurred <1 year (n = 11) and ≥ 1 year (n = 37). And 15 cases of primary non-resectable renal lesions received biopsy. The pathological types were clear cell carcinoma (n = 49) and papillary carcinoma (n = 14). The pre-dosing Karnofsky performance scores were all ≥ 70 points. Sorafenib was used as a first-line single drug at 400 mg twice daily until disease progression or an onset of intolerable adverse reactions. RESULTS: Follow-ups ended in February 2013. The median follow-up period was 20 (6-42) months. Twenty-four patients died. The outcomes were complete remission (n = 2), partial remission (n = 8), stable disease (n = 30) and disease progression (n = 23). The overall objective response rate was 15.9% (10/63) and disease control rate 63.5% (40/63) . Hand-foot skin reaction (70.0%), alopecia (62.5%), rash (52.5%), diarrhea (37.5%), loss of appetite (32.5%) and fatigue (27.5%) were noted. Most adverse reactions occurred at 2-4 weeks and subsided after symptomatic measures. And medication was not disrupted. CONCLUSION: Sorafenib has a high disease control rate for advanced renal cell carcinoma. And its adverse reactions are generally mild and similar to those reported in the literature. It has excellent profiles of tolerability and safety.