Paclitaxel Inhibits Proliferation by Negatively Regulating Cdk1-Cell Cycle Axis in Rat Airway Smooth Muscle Cells.

OBJECTIVE: Paclitaxel exhibits outstanding biological activities in inhibiting cell proliferation and inducing cell apoptosis. But the effects of paclitaxel on airway smooth muscle cells (ASMCs) have not been reported yet. The purpose of this study is to determine the effects of paclitaxel on the proliferation and apoptosis of ASMCs. METHODS: Rat primary ASMCs were isolated and used in all the experiments. Cell Counting Kit-8 (CCK-8) assay and Edu assay were used to analyse the cell viability and proliferation respectively. Flow cytometry was used to detect the cell cycle and apoptosis. Quantitative real-time PCR (qRT-PCR), western blotting, and immunostaining were used to detect the expression of Cyclin-dependent kinase 1 (Cdk1). RESULTS: Our study showed that paclitaxel inhibits the proliferation of ASMCs in a dose and time gradient dependent manner. Further study displayed that cell cycle is arrested at G2/M phase. And Cdk1 was dramatically down-regulated by paclitaxel treatment. Cell morphological analysis showed that ASMCs are elliptical with a larger surface area after paclitaxel treatment. Nucleus morphological analysis showed that the nuclei are in a diffuse state after paclitaxel treatment. But paclitaxel did not induce the apoptosis of ASMCs. CONCLUSIONS: Our study demonstrated that paclitaxel inhibits the proliferation of ASMCs at least partly by negatively regulating Cdk1-cell cycle axis.

An Evaluation of the Physicochemical Properties of Sesame Paste Produced by Ball Milling Compared against Conventional Colloid Milling.

The physicochemical characteristics and general food quality were greatly impacted by milling. In order to investigate the effect of milling technique for physicochemical properties of sesame paste of sesame paste, samples were prepared using ball mill and colloid mill by varying grinding times. The samples prepared by ball milling had the higher moisture contents (0.07% - 0.14%) than colloid milling (p < 0.05), except for colloid milling for one cycle (0.11%). The particle size curves showed the multimodal distributions. Compared to colloid milled samples, ball milled samples have smaller particle sizes and more uniform particle distribution. The L* values of samples prepared by ball milling were higher than colloid milling. The ball mill produced sesame paste with a wider range of hardness and silkier texture, and the samples made by ball milling for 30 min had the highest hardness. And the hardness of both CMS and BMS showed a decreasing trend with increasing grinding time. During ball milling, high-speed cutting and collision caused breakage of disulfide bonds, and the sesame proteins were decomposed to their subunits. In conclusions, ball milling may be an alternative and promising process for the preparation of sesame paste.

Effect of Dehulling Pretreatment on the Flavor of Sesame Paste.

Gas chromatography-olfactory-mass spectrometry (GC-O-MS) combined with Aroma Extract Dilution Analysis (AEDA) were employed to characterize the key odor-active compounds in sesame paste (SP) and dehulled sesame paste (DSP). The AEDA results revealed the presence of 32 and 22 odor-active compounds in SP and DSP, respectively. Furthermore, 13 aroma compounds with FD ≥ 2, OAV ≥ 1, and VIP ≥ 1 were identified as key differential aroma compounds between SP and DSP. Specifically, compounds such as 3-methylbutyraldehyde (OAV = 100.70-442.57; fruity), 2-methylbutyraldehyde (OAV = 106.89-170.31; almond), m-xylene (FD = 16; salty pastry), and 2,5-dimethylpyrazine (FD = 8-16; roasted, salty pastry) played an important role in this differentiation. Additionally, the dehulling process led to increased fermented, sweet, green, and nutty aroma notes in DSP compared to the more pronounced burnt and roasted sesame aroma notes in SP. Our findings offer a theoretical foundation for the regulation of sesame paste aroma profiles.

Toll-like receptor 4 mediated autophagy regulates airway smooth muscle cells behavior.

OBJECTIVES: Airway remodeling, a prominent feature of asthma, involves aberrant proliferation, apoptosis, and migration of airway smooth muscle cells (ASMCs). Toll-like receptors (TLRs) are implicated in the regulation of the autophagy pathway. In this study, we aimed to investigate the influence of Toll-like receptor 4 (TLR4) on autophagy and its underlying mechanism in ASMC proliferation, apoptosis, and migration. METHODS: Histopathological changes in the lungs of asthmatic mice assessed by Hematoxylin-Eosin (HE) and Masson staining. Cell proliferation, apoptosis and migration were evaluated utilizing CCK8, Edu, Flow cytometry and wound heading assays. The effectiveness of siRNA transfection and the expression of TLR4, autophagy, and proliferation-related proteins after siRNA treatment were examined through RT-PCR and Western blot (WB). CONCLUSION: We observed an increase in TLR4 expression and autophagy in a mouse model of OVA-induced asthma. In vitro experiments showed that siRNA-mediated inhibition of TLR4 suppressed autophagy, proliferation, and migration of ASMCs, whereas TLR4 activation by lipopolysaccharide (LPS) had the opposite effect. Furthermore, the autophagy inhibitor 3-Methyladenine (3MA) inhibited ASMCs proliferation and migration while promoting apoptosis. Significantly, our study demonstrated that autophagy inhibition reversed the promotion effect of LPS on ASMC proliferation and migration. These findings suggest that TLR4 may modulate ASMC behavior through the regulation of autophagy.

Moisture content in dehulled sesame seeds: A key factor affecting the aroma and safety quality of sesame paste (tahini).

This study aimed to investigate the influence of the moisture content of dehulled sesame seeds on the aroma formation and harmful substances in sesame paste (SP). The SP samples were made of dehulled sesame seeds with moisture contents of 5%, 10%, 15%, 20%, and 25% and denoted as T5, T10, T15, T20, and T25, respectively. The results revealed that adjusting the moisture content had a significant impact on aroma compounds, color intensity, and sensory properties. SP pre-adjusted to a moisture content of 10% exhibited the smallest L* value and the highest browning strength. Using gas chromatography-olfactometry-mass spectrometry analysis, the researchers identified 38 aroma-active compounds in the SP, with pyrazines being the most abundant, contributing to roasted sesame and nutty aromas. Additionally, the presence of pyrrole and furan derivatives led to enhanced caramel and almond aromas, positively influencing the overall sensory properties. T10 demonstrated the highest levels of roasted sesame and nutty odors. Furthermore, the regulation of moisture content also affected the formation of harmful compounds, such as heterocyclic amines and polycyclic aromatic hydrocarbons (PAHs). Notably, the sample made of the sesame seeds with 10% and 15% moisture content exhibited the lowest total PAHs content (18.21-28.91 ng/g) and PAH4 content (non-detectable-0.15 ng/g). The carcinogen benzo[a]pyrene was not detected in any of the samples, ensuring a safer product. The pre-adjustment of moisture content in SP appears to be a promising approach to improve both its flavor and safety qualities.

Assessment of Mononuclear/Dinuclear copper acylhydrazone complexes for lung cancer treatment.

Non-platinum metal-based complexes have good potential for cancer treatment. Here, we designed and synthesized five hydrazone copper(II) complexes, [Cu2(HL)2Cl2] 1A, [Cu2(HL)2(NO3)H2O]·NO3 2A, [Cu2(HL)2Br2] 3A, [Cu(L)pyridine] 1B and [Cu(HL)(pyridine)Br] 3B, and evaluated their anti-lung cancer activities. MTT experiments revealed that these copper(II) complexes exhibit higher anticancer activity than cisplatin. Mechanism studies revealed that complex 3A induced G1 phase cell cycle arrest, and induced cell apoptosis via reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Scratch wound healing assay was also performed, revealing that complex 3A have good anti-cell migration activity. Hemolysis assays showed good blood biocompatibility of complex 3A. Furthermore, complex 3A can significantly inhibit the proliferation of A549 3D tumor spheroid. An in vivo anticancer study showed that complex 3A could delays the growth of A549 tumor xenografts with lower systemic toxicity. These results highlight the great possibility of developing highly active copper complexes as anti-lung cancer agents.

Pre-regulation of the water content impacts on the flavor and harmful substances of sesame paste.

In this study, the influence of pre-regulation of the water content (5-25 %) on the harmful substances and aroma compounds of sesame paste (SP) was investigated. The results indicated that pre-regulation of the water content reduced the generation of harmful substances in SP. Notably, the total heterocyclic amine content in SP-15 was significantly lower than in other samples. SP-10 had the lowest total polycyclic aromatic hydrocarbon content, while SP-5 exhibited the lowest PAH4 content. Using solvent-assisted aroma evaporation and GC-O-MS, 50 aroma compounds were identified in SP. Pre-regulation of water content in SP led to an elevated concentration of heterocyclic compounds thereby imparting a diverse aromatic profile. It enhanced the perceived intensity of roasted sesame and salty pastry aromas while reducing the perceived intensity of fermentation and burnt aromas. The findings suggested the pre-regulation of the water content played a crucial role in aroma modulation and harmful substances control in SP.

Atomized inhalation of Icaritin reduces airway inflammation and remodeling in asthmatic mice.

BACKGROUND: Asthma is a disease characterized by airway hyperresponsiveness and airway inflammation. Icaritin (ICT) is a plant hormone with various pharmacological activities such as anti-inflammatory, immune regulation, and anti-tumor. This study mainly explored the effects of nebulized inhalation of ICT on airway inflammation and airway remodeling in asthmatic mice. METHOD: Different groups of ovalbumin (OVA)-induced asthma mice with acute and chronic airway inflammation received ICT. Asthmatic mice received budesonide (BDND) aerosol inhalation as a positive control, while normal control and asthma model mice received the same volume of saline. Following finishing of the study, analyses were conducted on behavioral tests, biochemical indices, and histological structures of lung tissues. RESULTS: Aerosol inhalation of ICT can notably reduce inflammatory cells infiltration around the airways and pulmonary vessels, and suppressed goblet cell hyperplasia in asthmatic mice. Long-term inhalation of ICT can decrease airway collagen deposition and airway smooth muscle hyperplasia, and alleviate airway hyperresponsiveness, mirroring the effects observed with hormone employed in clinical practice. CONCLUSION: Nebulized inhalation of ICT can effectively inhibit airway inflammation in asthmatic mice, improve airway remodeling, and reduce airway hyperresponsiveness, with effects similar to those of hormones. It may serve as a potential candidate used as a hormone replacement asthma treatment.

Transcription Factor VvDREB2A from Vitis vinifera Improves Cold Tolerance.

Low temperatures restrict the growth of the grapevine industry. The DREB transcription factors are involved in the abiotic stress response. Here, we isolated the VvDREB2A gene from Vitis vinifera cultivar 'Zuoyouhong' tissue culture seedlings. The full-length VvDREB2A cDNA was 1068 bp, encoding 355 amino acids, which contained an AP2 conserved domain belonging to the AP2 family. Using transient expression in leaves of tobacco, VvDREB2A was localized to the nucleus, and it potentiated transcriptional activity in yeasts. Expression analysis revealed that VvDREB2A was expressed in various grapevine tissues, with the highest expression in leaves. VvDREB2A was induced by cold and the stress-signaling molecules H2S, nitric oxide, and abscisic acid. Furthermore, VvDREB2A-overexpressing Arabidopsis was generated to analyze its function. Under cold stress, the Arabidopsis overexpressing lines exhibited better growth and higher survival rates than the wild type. The content of oxygen free radicals, hydrogen peroxide, and malondialdehyde decreased, and antioxidant enzyme activities were enhanced. The content of raffinose family oligosaccharides (RFO) also increased in the VvDREB2A-overexpressing lines. Moreover, the expression of cold stress-related genes (COR15A, COR27, COR6.6, and RD29A) was also enhanced. Taken together, as a transcription factor, VvDREB2A improves plants resistance to cold stress by scavenging reactive oxygen species, increasing the RFO amount, and inducing cold stress-related gene expression levels.

Effect of Flaxseed Addition on the Quality and Storage Stability of Sesame Paste.

The flaxseed-sesame paste (FSP) was prepared by mixing the heat-treated flaxseed and sesame seeds in different proportions and grinding them in a colloid mill to obtain a FSP. In this study, flaxseed was added to sesame paste (SP) at different addition to assess its effect on the rheological properties, textural properties, and particle size. The effect of flaxseed addition on lipid oxidation and volatile aldehydes and ketones during storage of SP was investigated by accelerated oxidation experiments (63°C, 60 days). Notably, the addition of all different additions of flaxseed increased the linolenic acid content, and also enhanced the hardness, cohesiveness, and viscosity of SP. However, it increased the rate of lipid oxidation in SP during storage, mainly in the form of higher acid value (AV) and malondialdehyde (MDA) content. The content of volatile aldehydes and ketones from lipid oxidation increased significantly with storage time. It was found by using cluster analysis that mixing flaxseed with SP at a ratio of 20 g/100 g had little effect on its storage stability, the sample had a higher overall quality than the addition of 40 g/100 g flaxseed, and its linolenic acid content was 18.7 times higher than that of the SP. Collectively, the results indicated that the addition of flaxseed at an appropriate proportion might be a feasible way to prepare the functional formulated SP.

Thermal and Dielectric Properties of Wolfberries as Affected by Moisture Content and Temperature Associated with Radio Frequency and Microwave Dehydrations.

Knowledge of the thermal and dielectric properties of wolfberries is essential for understanding the heat transfer and the interaction between the electromagnetic field (10-3000 MHz) and the sample during radio frequency (RF) and microwave (MW) drying. The thermal and dielectric properties of wolfberries were determined as influenced by moisture content from 15.1% to 75.2%, w.b.) and temperature from 25 to 85 °C. The results showed that as the moisture content increased from 15.1% to 75.2% (w.b.), the true density of wolfberries decreased, but the specific heat capacity and thermal conductivity increased with increasing temperature and moisture content. The dielectric properties (DPs) of wolfberries decreased with increasing frequency from 10 to 3000 MHz. The dielectric constant increased with increasing temperature at lower a moisture content (below 45% w.b.) but decreased with increasing temperature at a high moisture content (above 60% w.b.). The cubic and quadratic polynomial models (R2 = 0.977 - 0.997) were best for fitting the dielectric constant and loss factor at four representative frequencies of 27, 40, 915, and 2450 MHz, respectively. The penetration depth increased with the decreased frequency, temperature, and moisture content, and was greater at RF frequencies than MW range, making the RF heating more effective for drying bulk wolfberries. These findings offered essential data before optimizing RF or MW dehydration protocols for wolfberries via computer simulation.

Correlation analysis of intestinal flora and immune function in patients with primary hepatocellular carcinoma.

Background: This study applied metagenomic sequencing technology to analyze the intestinal flora distribution and immune function of patients with primary liver cancer. Methods: Stool samples were collected from 10 patients with primary liver cancer (primary liver cancer group) and 10 healthy subjects (healthy control group) who were admitted to The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from March to June 2021. The general data of the patients were recorded. Metagenomic sequencing was performed, and principal component analysis and diversity analysis were used to analyze the structure of the two groups and compare the differences in species abundance. United States Employment Service (USES) Spearman correlation analysis was applied to examine vice Streptococcus blood, saliva, Streptococcus, Streptococcus mutans, Streptococcus thermophilus, and vice Haemophilus influenzae, WeiRong aureus, existing different WeiRong bacteria, Eosinophilic mucins Ekman bacteria, responding to bacteria, the other branch bacteria abundance and in alanine aminotransferase (ALT), aspartate aminotransferase (AST), valley correlation between levels of amyltranspeptidase (GGT), total protein, total bilirubin and alpha-fetoprotein (AFP). Results: Beta diversity analysis based on Bray and Jensen-Shannon Divergence (JSD) distance measurement showed that the heterogeneity of fecal flora in the hepatic cell carcinoma (HCC) group was significantly lower than that in the healthy control group (P<0.001. At the species level of bacterial taxonomy, there was a statistically significant difference in the distribution of 137 bacteria in the healthy control and primary liver cancer groups (P<0.05). Correlation analysis showed that Streptococcus salivarius (P=0.020), Streptococcus thermophilus (P=0.002), and Haemophilus parainfluenzae (P=0.023) were significantly positively correlated with the serum ALT level. There were also notable correlations with AST (P=0.049), GGT (P=0.037), and total protein (P=0.010). Conclusions: The diversity of intestinal flora in patients with primary liver cancer is significantly reduced, species abundance is altered, and there is a marked imbalance of intestinal flora. Therefore, specific bacterial species with different intestinal flora may be used as biomarkers for the early diagnosis of primary liver cancer.

A NAC Transcription Factor from 'Sea Rice 86' Enhances Salt Tolerance by Promoting Hydrogen Sulfide Production in Rice Seedlings.

Soil salinity severely threatens plant growth and crop performance. Hydrogen sulfide (H2S), a plant signal molecule, has been implicated in the regulation of plant responses to salinity stress. However, it is unclear how the transcriptional network regulates H2S biosynthesis during salt stress response. In this study, we identify a rice NAC (NAM, ATAF and CUC) transcription factor, OsNAC35-like (OsNACL35), from a salt-tolerant cultivar 'Sea Rice 86' (SR86) and further show that it may have improved salt tolerance via enhanced H2S production. The expression of OsNACL35 was significantly upregulated by high salinity and hydrogen peroxide (H2O2). The OsNACL35 protein was localized predominantly in the nucleus and was found to have transactivation activity in yeast. The overexpression of OsNACL35 (OsNACL35-OE) in japonica cultivar Nipponbare ramatically increased resistance to salinity stress, whereas its dominant-negative constructs (SUPERMAN repression domain, SRDX) conferred hypersensitivity to salt stress in the transgenic lines at the vegetative stage. Moreover, the quantitative real-time PCR analysis showed that many stress-associated genes were differentially expressed in the OsNACL35-OE and OsNACL35-SRDX lines. Interestingly, the ectopic expression of OsNACL35 triggered a sharp increase in H2S content by upregulating the expression of a H2S biosynthetic gene, OsDCD1, upon salinity stress. Furthermore, the dual luciferase and yeast one-hybrid assays indicated that OsNACL35 directly upregulated the expression of OsDCD1 by binding to the promoter sequence of OsDCD1. Taken together, our observations illustrate that OsNACL35 acts as a positive regulator that links H2S production to salt stress tolerance, which may hold promising utility in breeding salt-tolerant rice cultivar.

Hydrogen Sulfide Alleviates Manganese Stress in Arabidopsis.

Hydrogen sulfide (H2S) has been shown to participate in various stress responses in plants, including drought, salinity, extreme temperatures, osmotic stress, and heavy metal stress. Manganese (Mn), as a necessary nutrient for plant growth, plays an important role in photosynthesis, growth, development, and enzymatic activation of plants. However, excessive Mn2+ in the soil can critically affect plant growth, particularly in acidic soil. In this study, the model plant Arabidopsis thaliana was used to explore the mechanism of H2S participation and alleviation of Mn stress. First, using wild-type Arabidopsis with excessive Mn2+ treatment, the following factors were increased: H2S content, the main H2S synthetase L-cysteine desulfhydrase enzyme (AtLCD) activity, and the expression level of the AtLCD gene. Further, using the wild-type, AtLCD deletion mutant (lcd) and overexpression lines (OE5 and OE32) as materials, the phenotype of Arabidopsis seedlings was observed by exogenous application of hydrogen sulfide donor sodium hydrosulfide (NaHS) and scavenger hypotaurine (HT) under excessive Mn2+ treatment. The results showed that NaHS can significantly alleviate the stress caused by Mn2+, whereas HT aggravates this stress. The lcd mutant is more sensitive to Mn stress than the wild type, and the overexpression lines are more resistant. Moreover, the mechanism of H2S alleviating Mn stress was determined. The Mn2+ content and the expression of the Mn transporter gene in the mutant were significantly higher than those of the wild-type and overexpression lines. The accumulation of reactive oxygen species was significantly reduced in NaHS-treated Arabidopsis seedlings and AtLCD overexpression lines, and the activities of various antioxidant enzymes (SOD, POD, CAT, APX) also significantly increased. In summary, H2S is involved in the response of Arabidopsis to Mn stress and may alleviate the inhibition of Mn stress on Arabidopsis seedling growth by reducing Mn2+ content, reducing reactive oxygen species content, and enhancing antioxidant enzyme activity. This study provides an important basis for further study of plant resistance to heavy metal stress.

Comparative assessment of the effect of pretreatment with microwave and roast heating on the quality of black sesame pastes.

Heating is a key procedure in producing sesame paste. The effects of microwave heating and conventional roasting on the physicochemical features, protein profiles, and volatile compounds of black sesame pastes made of black sesame seeds from Burma and China were evaluated in this study. All heating treatments decreased the moisture contents of black sesame pastes, and roasting yielded lower moisture levels, although with similar chroma (p < 0.05). The samples subjected to microwave heating had remarkably lower peroxide values than those heated with roasting (p < 0.05). Chinese microwave-heated samples had a higher nitrogen solubility index than roasting (p < 0.05). Both microwave and roasting increased the contents of the volatiles notably. SDS-PAGE showed that the intensity of the 2-15 kDa band decreased markedly after heating and nearly diminished for roasting samples, suggesting that roasting was more remarkable for the promotion to the protein aggregation. The results indicated that the quality traits of black sesame paste not only depend on the heating methods, but also the heating power/temperature and duration, and the source of the materials.

Identification of Key Amino Acid Residues Involved in the Localization of Sorting Nexin 10 and Induction of Vacuole Formation.

Sorting nexin 10 (SNX10) induces formation of vacuoles participating in the endosome morphogenesis in mammalian cells, but the key amino acids involved in this function have not been fully identified. In this study, point mutations were introduced to the conserved region of the SNX10 PX domain to elucidate the function of these key amino acid residues. The number of vacuoles in the R53A mutant was partially decreased, while the R52A and R51A mutants completely lacked the vacuoles. All mutant proteins lost the phosphatidylinositol 3-phosphate (PtdIns3P)-binding ability and endosomal localization. Retargeting the mutants to the endosomes rescued partially or fully the vacuole-inducing ability in the R51A and R53A mutants, respectively, but not in the R52A mutant. No vacuoles were induced when the R51A mutant was targeted to other organelles. Structural analysis showed that Arg53 is responsible for the PtdIns(3)P binding, whereas Arg51 and Arg52 contribute to the structural integrity of SNX10. We conclude that the disruption of the key residues affects the structure and function of SNX10 and that induction of vacuole formation by SNX10 depends on its endosomal location.

Trehalose inhibits proliferation while activates apoptosis and autophagy in rat airway smooth muscle cells.

Trehalose is a disaccharide with multiple important biological activities. In many cell types, Trehalose regulates the physiological behaviors of proliferation, apoptosis and autophagy. But the effects of trehalose on ASMCs have never been reported. Here, we showed that trehalose activated autophagy of ASMCs at low dose, inhibited proliferation and induced apoptosis of ASMCs at high dose. Further study, we found the cell cycle was arrested in S and G2\M phases, the expression of CyclinA1 and CyclinB1 decreased. Then, we investigated the ratio of Bcl-2/Bax was drastically reduced. Next, we detected an important transcription factor TFEB, which is closely related to autophagy. We found TFEB was highly activated with trehalose treatment. And many downstream autophagy-related genes of TFEB were also up-regulated. In summary, trehalose plays an important role on the regulation of proliferation, apoptosis and autophagy of ASMCs.

Effects of isolation conditions on structural and functional properties of the seed gum from Chinese quince (Chaenomeles sinensis).

Chinese quince seed gum (CQSG) extracted under water-, alkali- and acid- conditions at 25, 50, and 80 °C, were evaluated in terms of yield, monosaccharide composition, molecular distribution, thermal gravimetry, emulsifying stability, rheological properties, and free radical scavenging ability. The results showed that the yield of CQSG increased to 3.9% after water extraction at 80 °C. Alkali and acid treatments promoted the conversion of neutral sugars to the uronic acid branch. Regardless of the extraction temperature, the xylose chain was the main component (35%-40%); however, a reduction was observed as the extraction temperature increased to 80 °C. All CQSG solutions extracted under these isolation conditions exhibited non-Newtonian rheological behavior. Compared to water-extracted samples, the alkali-extracted samples showed the worst thermal stability, while the acid-treated samples showed the worst emulsifying stability. This study provides theoretical support for the potential application of CQSG polysaccharides in the food and pharmaceutical industries.

A retrospective study on the preventive effect of statin after carotid artery stenting.

ABSTRACT: This retrospective study appraised the preventive effect of statin after carotid artery stenting (CAS).Records were extracted for 100 patients with CAS surgery indicator, aged between 20 and 75 years old, and treated for statin. The cohort study included treatment group (statin and routine treatment) and control group (routine treatment), each group 50 patients. Outcomes consisted of degree of nerve defect (as measured by National Institute of Health Stroke Scale), lipid profiles (mg/dL), and CAS complications within 30 days after surgery.After treatment, there were no significant differences in National Institute of Health Stroke Scale, lipid profiles, and mortality rate between 2 groups. However, significant differences in total cholesterol (mg/dL, P = .03), low-density lipoprotein (mg/dL, P = .01), transient ischemic attack (P = .03), ischemic stroke (P = .04), and cardiac complications (P = .03) were identified within 30 days after CAS between 2 groups.The results of this study showed that prior statin treatment may be effective for the prevention of CAS complications.

Efficacy and Safety of Apatinib Treatment for Advanced Cholangiocarcinoma After Failed Gemcitabine-Based Chemotherapy: An Open-Label Phase II Prospective Study.

PURPOSE: As a novel small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), Methylsulfonic apatinib (apatinib) exhibits a specific antitumor effect in various solid tumors via inhibition of angiogenesis. The present study was performed to evaluate the clinical efficacy and safety of apatinib in the treatment of advanced cholangiocarcinoma after failed gemcitabine-based chemotherapy. PATIENTS AND METHODS: This was a prospective open-label phase II trial (NCT03521219). A total of 32 patients, in whom gemcitabine-based first-line chemotherapy for advanced intrahepatic cholangiocarcinoma had failed, were consecutively enrolled in a prospective, open, exploratory, and single-center clinical trial from November 2017 to November 2018. They were treated with apatinib mesylate second-line monotherapy (orally, 500 mg per day for a cycle of 28 days) until progressive disease or unacceptable toxicity. Using Response Evaluation Criteria in Solid Tumor version 1.1 (RECIST 1.1) and the Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE 4.0), the efficacy and adverse were evaluated, respectively. Kaplan-Meier method was used for survival analysis. RESULTS: Twenty-six patients were enrolled in full analysis set. At the end of follow-up, two patients were lost to follow-up, 24 of 26 patients in FAS were included in efficacy analyses. For the efficacy analysis set, the objective response rate (ORR) was 20.8% [95% confidence interval (CI): 9.24-40.47%] and the disease control rate (DCR) was 62.5% (95% CI: 112.86-387.14 days). One patient (4%) showed complete response (CR), 4 patients (17%) showed partial response (PR), 10 patients (41.7%) stable disease (SD), and 9 patients (37.5%) had progressive disease (PD). Meanwhile, apatinib therapy achieved the median progression-free survival PFS was 95 days (95% CI: 79.70-154.34 days), and the median OS was 250 days (95% CI: 112.86-387.14 days). Furthermore, univariate analysis revealed that age and tumor's anatomic location significantly affected PFS (P < 0.05). The most common clinically adverse events (AEs) included myelosuppression (69.2%), hypertension (57.7%), proteinuria (46.2%). The AEs were mild, mainly in grade 1 or 2, and no toxicity-induced death occurred. CONCLUSION: Apatinib monotherapy is an effective and promising regimen for treating patients with advanced cholangiocarcinoma who experienced failure of gemcitabine-based chemotherapy.