miR-149 promotes human osteocarcinoma progression via targeting bone morphogenetic protein 9 (BMP9).

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.

[Effect of total flavonoids from astragalus complanatus on paraquat poisoning-induced pulmonary fibrosis in rats and its mechanisms].

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-ß, 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-ß 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-ß/Smad signaling pathway.

First-Line Lenvatinib Plus Pembrolizumab or Everolimus versus Sunitinib for Advanced Renal Cell Carcinoma: A United States-Based Cost-Effectiveness Analysis.

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 cost-effectiveness 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.

First-line Immuno-chemotherapy for extensive-stage small-cell lung cancer: A network meta-analysis and cost-effectiveness analysis.

Introduction: Many randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients. Methods: Multiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-benefit ratio (ICER) were estimated by CEA. Results: We identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively. Conclusion: The NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.

Distinguishing urothelial carcinoma in the upper urinary tract from benign diseases with hematuria using FISH.

OBJECTIVE: The aims of this study were to evaluate the clinical utility of a fluorescence in situ hybridization (FISH) assay as a non-invasive molecular test to distinguish urothelial carcinoma (UC) in the upper urinary tract (UUT) from benign lesions presenting with hematuria. STUDY DESIGN: The chromosomal abnormalities of chromosomes 3, 7, 17 and 9 (p16) in hematuria specimens from 34 patients with UUT-UC and 33 patients with benign disorders were detected using a set of fluorescently labeled DNA probes. The abnormalities of the chromosomes were determined and analyzed between UUT-UC and benign disorders. RESULTS: Chromosomal abnormalities were detected in 25 of 34 (73.5%) patients with UUT-UC and in 2 of 33 (6.1%) patients with benign disorders (p < 0.001). CONCLUSIONS: FISH of chromosomes 3, 7, 9 and 17 performed on exfoliated cells from voided urine specimens may serve as a non-invasive tool to distinguish UUT-UC from benign disorders presenting with hematuria.

Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis.

Introduction: Two targeted drugs (apatinib and lenvatinib) show clinical efficacy in first-line treatment of Chinese patients with radioactive advanced iodine-refractory differentiated thyroid cancer (RAIR-DTC) and are recommended by the Chinese Society of Clinical Oncology guidelines. Considering the high clinical cost of long-term vascular endothelial growth factor receptor inhibitor administration and to determine which of the two targeted drugs is preferable, we opted to conduct a cost-effectiveness analysis (CEA) and network meta-analysis (NMA). Material and Methods: The results of NMA and CEA included in the two phase III randomized clinical trials REALITY (NCT03048877) and Study-308 (NCT02966093), in which Bayesian NMA and CEA were performed on 243 and 149 Chinese patients, respectively, were retrieved. Overall survival and progression-free survival (PFS) for apatinib versus lenvatinib were determined by NMA. CEA involved the development of a 20-year Markov model to obtain the total cost and quality-adjusted life-years (QALYs), and this was followed by sensitivity and subgroup analyses. Results: Compared with lenvatinib, apatinib therapy provided a 0.837 improvement in QALY and $6,975 reduction in costs. The hazard ratio of apatinib versus lenvatinib and the cost of the targeted drugs had a significant impact on the model. According to the sensitivity analysis, apatinib was more cost-effective and had no correlation with willingness-to-pay in China. Subgroup analysis showed that apatinib maintained PFS more economically. Conclusion: NMA and CEA demonstrated that apatinib was more cost-effective compared to lenvatinib in the first-line treatment of Chinese RAIR-DTC patients.

Pembrolizumab Plus Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A Cost-Effectiveness Analysis.

INTRODUCTION: In 2021, KEYNOTE-590 (NCT03189719) showed that pembrolizumab plus 5-fluorouracil and cisplatin (PPF) has more benefits than 5-fluorouracil and cisplatin (PF) as a first-line regimen to treat individuals with advanced esophageal cancer. However, given that it is expensive, controversies over the value of using this compared to competitive strategies remain. Hence, we conducted a cost-effectiveness evaluation of pembrolizumab plus chemotherapy. METHODS: A Markov model was applied in evaluating the efficacy and cost of PPF and PF over a 7-year horizon and measured the health outcomes in life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The economic data included were relevant to patients in the USA and China. We also performed one-way and probabilistic sensitivity analyses to determine the uncertainties relevant to the model. Willingness to pay thresholds (WTP) of $150,000/QALY (USA) and $35,673/QALY (China) were used to calculate a probability for the cost-effectiveness of PPF. RESULTS: PPF yielded 0.386-0.607 QALYs (0.781-1.195 LYs) compared with PF. In our analysis, compared with receiving PF, patients with advanced esophageal cancer receiving PPF had an ICER of $577,461/QALY in the USA and $258,261/QALY in China, those for esophageal squamous cell carcinoma were $550,211/QALY in the USA and $244,580/QALY in China, and a programmed cell death ligand 1 combined positive score (PD-L1 CPS) ≥ 10 was associated with a cost of $479,119/QALY in the USA and $201,355/QALY in China. Sensitivity analysis found the price of pembrolizumab to be the biggest influence. CONCLUSION: From the economic perspectives of the USA and China, a first-line regimen of PPF for esophageal cancer therapy may not be as cost-effective as PF. However, patients with esophageal cancer and PD-L1 CPS ≥ 10 may gain the most LYs from initial PPF treatment.

Sulfonated Sargassum horneri carbon as solid acid catalyst to produce biodiesel via esterification.

A solid acid catalyst prepared by sulfonated Sargassum horneri carbon was utilized for the esterification reaction of oleic acid and methanol. The formed amorphous carbon layers during carbonization and the access of sulfonic acid groups during sulfonation can catalyze the esterification reaction for biodiesel preparation efficiently. The catalyst was characterized by various methods to investigate its physical and chemical properties. With carbonization at 300 °C for 2 h followed by sulfonation at 90 °C for 5 h, the catalyst reached acid density of 1.40 mmol/g. The catalyst dosage, methanol/oleic acid (molar ratio), reaction temperature, and reaction time were optimized to 10 wt%, 15:1, 70 °C, and 3 h, respectively. Under the optimal condition, the conversion of oleic acid reached 96.4%. Additionally, the catalyst was regenerated after four cycles, with the conversion of oleic acid still reaching 95.4%.

Treatment of persistent hiccups after arthroplasty: effects of acupuncture at PC6, CV12 and ST36.

OBJECTIVE: There are multiple treatment options for hiccups, including non-pharmacological therapies, but little evidence of superiority of one treatment over another. The aim of this study was to investigate the effects of acupuncture on persistent hiccups after arthroplasty. METHODS: From April 2010 to December 2015, 15 patients with primary unilateral total hip/knee arthroplasty were diagnosed with persistent hiccups and given acupuncture at PC6, CV12 and ST36. Each acupuncture session lasted 30 min. The total number of treatment sessions was determined by the persistence of symptoms, but acupuncture was administered no more than three times over the course of a week. The hiccups assessment instrument (HAI) was used to assess the severity of hiccups pre-treatment and post-treatment. Adverse events were also recorded. RESULTS: Absolute resolution was observed in all 15 patients after less than three acupuncture sessions. Of these, 10 patients required only one acupuncture session, 3 patients required two sessions and 2 patients required three sessions. The HAI score improved after each round of acupuncture treatment (P<0.05). The average HAI score improved significantly post-acupuncture compared to baseline values pre-treatment (P<0.05). Symptoms accompanying the hiccups included pain in the diaphragmatic area (five patients), mild dyspnoea (three patients), dysphagia (two patients) and nausea/vomiting (one patient). All these accompanying symptoms disappeared at the point of resolution of the hiccups. There were no adverse effects related to acupuncture during the study period. CONCLUSION: Based on our results, acupuncture may represent a potential treatment option for hiccups after arthroplasty. Caution must be exercised, however, given the lack of a control group. Accordingly, randomised controlled trials will be required to verify the efficacy and effectiveness of acupuncture for the treatment of hiccups.

Room-temperature production of bio-based aldehydes from vegetable oil-derived epoxide via H2WO4@Al-MCM-41 as recyclable catalyst.

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 H2WO4 as the catalyst, H2O2 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 H2WO4 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 H2WO4 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.