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Lenvatinib plus pembrolizumab or everolimus have considerable clinical benefits. However, it is controversial whether the high-cost combination regimen will be approved by the guidelines and widely used in clinical practice. Based on current prices, lenvatinib plus pembrolizumab is a cost-effective treatment option. Our conclusions provide objective data reference for clinicians when making clinical decisions, individual treatment of patients, and reference for national health insurance decision-making. Introduction: The CLEAR trial indicated that survival benefits were generated with lenvatinib plus pembrolizumab (LP) or everolimus (LE) than with sunitinib for advanced renal cell carcinoma (aRCC). However, the high cost of immuno-target and dual-targeted treatment, we assessed the costeffectiveness of lenvatinib plus pembrolizumab or everolimus in the first-line setting for treatment of patients with aRCC from the United States (US) payers' perspective. Materials and Methods: A comprehensive Markov model was developed to evaluate the cost and effectiveness of LP or LE in first-line therapy for aRCC. We estimated life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Utility values and direct costs related to the treatments were gathered from the published studies. Then, one-way and probabilistic sensitivity analyses were performed. Additional subgroup analyses were considered. Results: Treatment with LP and LE provided an additional 0.67 QALYs (0.62 LYs) and 0.66 QALYs (0.90 LYs) compared with sunitinib, resulting in ICER of $131,656 per QALY and 201,928 per QALY, respectively. The most influential factor in this model was the cost of pembrolizumab with LP. Probabilistic sensitivity analysis showed there was a 58.97% and 28.91% probability that LP and LE were cost-effective at WTP values of $150,000 per QALY in the US. Subgroup analyses demonstrated that LP was more cost-effective for patients from Western Europe and North America, intermediate risk of the International risk group of Metastatic Renal Cell Carcinoma Database Consortium (IMDC), favorable and intermediate risk group of Memorial Sloan Kettering Cancer Center (MSKCC) and PD-L1 combined positive score greater than or equal to 1%. Conclusion: From the perspective of the US payer, LP is a cost-effective option as first-line treatment for patients with aRCC at a WTP threshold of $150,000 per QALY, but LE is the opposite. [ABSTRACT FROM AUTHOR]

At present, the utilization of grease has attracted more and more attention. This article presents a simple method that efficiently cleaves methyl oleate‐derived methyl 9,10‐epoxystearate (a) to give high yields of methyl 9‐oxononanoate (d) with nonanal (c) as co‐product. A WO3/MCM‐41 catalyst is prepared via direct mixed‐gel synthesis. The catalyst is tested in the oxidative cleavage of a to produce d which can be used as a polymer precursor or an important feedstock. The effects of WO3 loading, temperature, time, H2O2/a molar ratio, catalyst/a weight ratio, and t‐BuOH/a weight ratio on the a conversion and d yield are examined using single‐factor experiments. The optimal reaction conditions are determined by orthogonal experiments. The optimal WO3 loading, temperature, time, H2O2/a molar ratio, catalyst/a weight ratio, and t‐BuOH/a weight ratio are 35%, 80 °C, 20 min, 1.3, 0.04, and 0.5, respectively. Under these conditions, the a conversion and d yield reach 99.4 and 78.4%, respectively. In addition, the catalyst shows no significant decrease in activity after being reused three times. Moreover, the reaction mechanism is studied based on the product distribution over time. Practical Applications: Few studies on methyl 9,10‐epoxystearate used as the raw material to give methyl 9‐oxononanoate and nonanal are found. Because the ethylene oxide bond is more unstable than the carbon–carbon double bond, the oxidative cleavage of methyl 9,10‐epoxystearate is easier than cleavage of methyl oleate that allows the oxidative cleavage to be done under milder conditions. Methyl 9‐oxononanoate can be converted to a monomer of high‐value polymers and is also an important feedstock in the production of chemicals. The co‐product nonanal is a natural spice which can be used in the fragrance industry. The results show that the reaction time is short and methyl 9‐oxononanoate yield is high under mild reaction conditions. The method in this study can also be widely used in other oxidative cleavage reactions of epoxides. Methyl 9,10‐epoxystearate is used as the raw material to produce methyl 9‐oxononanoate with nonanal as co‐product using WO3/MCM‐41 as catalyst and H2O2 as oxidant. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the roles of miR-149 in the progression of human osteosarcoma (OS).Results: miR-149 level was upregulated in tissues from OS patients more than in normal subjects. Cell proliferation and apoptosis assays revealed that miR-149 increased cell proliferation and inhibited cell apoptosis in OS cell line (MG63). An increase of Bcl-2 gene expression and a decrease of cleaved-caspase-3, and cleaved-PARP expression were observed in MG63 cells with transfection of miR-149. Additionally, bone morphogenetic protein 9 (BMP9) was identified as a target of miR-149 in MG63 cells, and BMP9 expression was negatively correlated with miR149 level in OS clinical samples. Co-overexpression of BMP9 with miR-149 in MG63 cells prohibited miR-149-mediated promotive effects on OS progression. Importantly, overexpression of miR-149 conferred chemoresistance in MG63 cells.Conclusions: miR-149 promotes OS progression via targeting BMP9. [ABSTRACT FROM AUTHOR]

Background: Due to the adverse effects of cemented hip arthroplasty, uncemented stems with hydroxyapatite (HA) coating reduces these risks and enhanced integration. The concept of an extensive HA coating for the fixation of a tapered femoral stem (Corail) was introduced, which can achieve durable biological fixation and preserve normal periprosthetic bone activity. Here we describe the clinical and radiological outcome in patients with the Corail stem. Methods: 92 total hip replacements in 81 patients using the Corail stem were followed-up. 47 patients were women, and the mean age at surgery was 62.9 ± 8.7 (34-71) years. The indications included: osteoarthritis of the hip (71.1%), avascular necrosis (13.6%), femur neck fractures in elderly (9.7%) and post-traumatic osteoarthritis (6.8%). Findings: Eight patients died during follow-up. The revision was only found in two patients due to line wear and resulted in an 10-year Kaplan-Meier estimated overall survival rate of 97.83%. The clinical results were good, with a mean Harris hip score of 92.3 ± 5.6 (72-100). The mean total Merle d'Aubigné and Postel score was 6.8 ± 0.5 pre-operatively and 16.1 ± 1.4 at latest follow-up. All unrevised implants were radiographically stable, with a mean liner wear of 0.07 mm/year. Conclusion: This long-term analysis confirmed the durability of the functional and radiographic results. Our findings suggest the long-term results of Corail HA-coated stem are more satisfactory which is preferable to any other system. [ABSTRACT FROM AUTHOR]

The oxidative cleavage of vegetable oils and their derivatives to produce bio-based aldehydes is a potentially useful process, although the aldehyde products are readily oxidized to carboxylic acids and thus seldom obtained in high yields. The present study developed a room-temperature method for the synthesis of bio-aldehydes via the oxidative cleavage of vegetable oil-derived epoxides, using H 2 WO 4 as the catalyst, H 2 O 2 as the oxidant, and t -BuOH as the solvent. Reactions were carried out at temperatures ranging from 25 to 35 °C for 3.5-10.5 h, and provided >99% conversion and >90% aldehyde yield. In particular, an approximately 97% yield was obtained at 25 °C after 10.5 h. As the reaction proceeded, the H 2 WO 4 dissolved to form a W-containing anion. Several mesoporous Al-MCM-41 materials having different Si/Al ratios were hydrothermally synthesized and used as adsorbents to recover the catalyst by adsorbing these anions. The adsorption capacity of the Al-MCM-41 was found to increase with decreases in the Si/Al ratio. The Al-MCM-41 had little effect on the oxidative cleavage reaction at 25 °C, and thus could be directly added to the reaction system. The excellent anion adsorption performance of the Al-MCM-41 greatly improved the reusability of the H 2 WO 4 catalyst. When using the Al-MCM-41 with the best adsorption performance, there was no significant decrease in the activity of the catalyst following five reuses., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To investigate the effects of total flavonoids from astragalus complanatus (FAC) on paraquat poisoning-induced pulmonary fibrosis in rats., Methods: The rats were divided into six groups randomly: control group, paraquat group, prednisolone group and FAC low-dose, middle-dose, high-dose group. Pulmonary fibrosis model was replicated by intratracheal injection of paraquat. In the mext day,the rats were treated by intragastric administration once a day. After 28 days, the rats were sacrificed. The lung index and the levels of HYP and T-AOC were measured, and the pathologic changes of the lung tissue were obtained by HE staining. The levels of TGF-β, Smad2, α-SMA protein were analyzed by Western blot., Results: FAC improved the activity of T-AOC in serum and reduced pulmonary index and the content of HYP as well (P<0.05 or P<0.01), the alveolitis and fibrosis extent were attenuated. The expression of Smad2 significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.45±0.12 and 0.30±0.05) as compared with that of the PQ group (0.85±0.34) (P<0.05). The expression of α-SMA significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.31±0.11, 0.35±0.07 and 0.32±0.10) as compared with that of the PQ group (0.45±0.08) (P<0.05). The expression of TGF-β significantly decreased in groups of FAC low-dose, middle-dose and high-dose (0.35±0.04, 0.27±0.05 and 0.18±0.04)as compared with that of the PQ group (0.63±0.11) (P<0.05)., Conclusion: FAC can alleviate PQ-induced pulmonary fibrosis in rats through inhibiting TGF-β/Smad signaling pathway.

Objective: To investigate the effect of total flavonoids from astragalus complanatus (FAC) on attenuating lung injury resulted from paraquat (PQ) poisoning by inhibiting excessive endoplasmic reticulum stress (ERS) and c-Jun N-terminal kinase (JNK) pathway in rat., Methods: Forty-eight Sprague-Dawley (SD) rats were randomly divided into six groups (n=8 in each group), including control group, model group, dimethyl sulfoxide (DMSO) vehicle control group, and FAC in low, medium, and high dosage groups. The model was reproduced by giving PQ 80 mg/kg orally to induce lung injury. The rats in control group were treated with saline by gavage. The rats in DMSO group were given 10% DMSO 20 mL/kg by gavage 2 hours before intraperitoneal injection of PQ, and those in FAC low, medium and high dosage groups received 40, 80, 160 mg×kg(-1)×d(-1) of FAC solution intraperitoneally after the PQ administration. The rats were sacrificed 72 hours after giving PQ, and the left lung tissue was harvested 72 hours after the reproduction of experimental model. The ratio of wet/dry weight (W/D) and total lung water content (TLW) were determined. The pathohistological changes of the left lung was observed under light microscope, and scored with alveolar damage index of quantitative assessment (IQA). The mRNA expressions of JNK and glucose regulated protein 78 (GRP78) were determined by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of JNK, phosphorylation-JNK (p-JNK), and GRP78 were determined by Western Blot., Results: Compared with control group, the W/D ratio, TLW and IQA were increased significantly in model group and DMSO group, and the mRNA expressions of JNK and GRP78 and the protein expressions of JNK, p-JNK and GRP78 were markedly increased. Compared with the model group, the W/D ratio, TLW and IQA, and the expressions of JNK mRNA and p-JNK protein were significantly decreased in the FAC groups, especially in FAC high dosage group [W/D ratio: 3.0±0.3 vs. 5.5±0.5, TLW: 2.2±0.3 vs. 4.7±0.4, IQA: (15.4±3.0)% vs. (40.0±5.7)%, JNK mRNA: 0.21±0.08 vs. 0.82±0.27, p-JNK protein: 0.31±0.09 vs. 0.78±0.25, all P<0.01]. The mRNA expression of GRP78 and the protein expressions of JNK and GRP78 were highly expressed in FAC low, medium and high dosage groups, and there was no significant difference compared with those in model group (GRP78 mRNA: 0.54±0.18 vs. 0.74±0.20, JNK protein: 0.76±0.27 vs. 0.80±0.28, GRP78 protein: 0.51±0.18 vs. 0.69±0.21, all P>0.05)., Conclusions: PQ induces excessive ERS in the lung tissue resulting in lung injury. FAC has a protective effect on lung against PQ injury, and it may be related with inhibition JNK pathway in ERS.

The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine kinases regulates a multitude of physiological and pathological processes. EphA1 is the first member of Eph superfamily and is involved in carcinogenesis. The aim of this study was to investigate the expression of EphA1 in prostate cancers cell lines and the tissues, then explore the correlation with the clinicopathologic parameters. The EphA1 transcript expression in prostate cancer cell lines was detected by Quantitative real-time PCR. The expression of EphA1 protein in 138 prostate cancer tissue samples and 21 benign prostate hyperplasia samples were checked by using immunohistochemical staining. EphA1 mRNA was high expressed in LNCap, moderately expressed in 22RV1 and Du145, and lost in PC3. Loss of expression of EphA1 transcript was related to hypermethylation of CpG island around the translation start site. EphA1 protein was differentially expressed in prostate cancers and hyperplasia. Increased expression of EphA1 protein was more frequently detected in prostate cancers than in hyperplasia (P = 0.02), and more often detected in prostate cancer with high Gleason score (P < 0.001). Our data indicate that EphA1 receptor may have roles in carcinogenesis and progression of prostate cancer, and can be a potentially useful target for prognostic and therapeutic application.

We report a case of diffuse hyperplastic mesothelial cells in multiple lymph nodes. Microscopically, the lymph nodes had a normal follicular pattern. The lymphatic sinus was extremely expanded, within the sinuses the epithelial-like cells proliferated actively in the form of sheets and clusters. Epithelioid-like cells had eosinophilic cytoplasm, prominent nucleoli and vesicular nuclei. Mitotic figures were rarely observed. These cells were immunopositive for Calretinin, CK5/6, D2-40, MC and Ckpan and immunonegative for S-100, HMB45, MelanA, TTF-1, CDX-2, Villin, ALK, CD30, CD20, CD3, CD1a and CD68. In addition, during a 22 months follow-up period failed to identify any malignant neoplasms, thus confirming the benign nature of these cells. It is the first reported case of diffuse hyperplastic of mesothelial cells mainly in the cervical lymph nodes associated with systemic multiple lymph node involvement. Awareness of this event is important for the pathologist in preventing the misdiagnosis of malignancy.