Phase II study of apatinib plus exemestane in estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer.

PURPOSE: Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR)-2. This study was conducted to assess the efficacy and safety of apatinib combined with exemestane in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). METHODS: This single-center, single-arm phase II study enrolled patients with ER+/HER2- MBC progressed on previous letrozole or anastrozole. Stratified analysis was performed according to the number of chemotherapy regimens for metastatic disease. The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and toxicity. Patients received apatinib at a starting dose of 500 mg/d and exemestane 25 mg/d on days 1-28 of each 4-week cycle. RESULTS: Thirty patients were enrolled with median four prior anticancer therapies. Eighty percent of patients received chemotherapy for metastatic disease. The median PFS (mPFS) and OS were 5.6 (95%CI: 4.3-6.9) months and 15.7 (95% CI: 9.7-21.7) months, respectively. The ORR, DCR, and CBR were 21.4%, 71.4%, and 46.4%, respectively. Patients with 0-1 line chemotherapy for MBC showed a slightly longer mPFS compared to those with ≥2 lines chemotherapy (mPFS: 6.4 months vs 4.8 months, P = .090). Most of the AEs were grade 1/2. One patient (3.3%) who suffered bone marrow metastases experienced grade 4 thrombocytopenia, and 14 experienced grade 3 AEs. Fifty percent of patients were given reduced dose for apatinib. CONCLUSIONS: Apatinib plus exemestane exhibited objective efficacy in patients with ER+/HER2- MBC who have failed multiple lines of treatment. The AEs of apatinib required close monitoring and most of patients were well tolerated.

A therapeutic probe for detecting and inhibiting ONOO- in senescent cells.

Aging is an inevitable biological process, characterized by a general decline in the quality of all physiological functions and reactions involving all organs and tissues of the body. Oxidative stress is considered to be the main cause of aging, which may be caused by active nitrogen substances. ONOO- is one of the important active nitrogen substances. Therefore, detecting the changes of ONOO- in senescent cells is of great significance for the study of senescence. However, the study of ONOO- in senescent cells is not deep enough. Here, we designed and synthesized a fluorescent probe FLASN based on flavonol, which integrates ONOO- detection and aging treatment. Our probe FLASN was prepared by a simple synthesis process and was shown to have excellent spectral characteristics. Meanwhile, the results of bioimaging showed that the probe FLASN could detect endogenous/exogenous ONOO- in cells and in vivo, and could reduce the production of ONOO- in cells and in vivo stimulated by metformin. It is worth noting that for the first time, the change of ONOO- in senescent cells and in vivo was detected, and the therapeutic effect of flavonol on senescent cells and in vivo was confirmed, by using the probe FLASN.

Comparison of efficacy and safety between aspirin and oral anticoagulants for venous thromboembolism prophylaxis after major orthopaedic surgery: a meta-analysis of randomized clinical trials.

Background: venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used. Objectives: To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS). Methods: Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration's tool. Results: After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053-1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499-1.815), all-cause mortality (RR = 1.208, 95% CI 0.459-3.177), and wound-related events (RR = 0.618, 95% CI 0.333-1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552-0.850) events and total bleeding (RR = 0.726, 95% CI 0.590-0.892). Conclusion: Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.

A fluorescent probe for the detection of N2H4 in solution, steam, and the biological system.

Improper use of N2H4 will cause serious harm to the environment. Inhalation or skin contact with N2H4 will also cause a variety of diseases for humans and animals. Herein, a fluorescent probe (HFOAc) for the detection of N2H4 in solution, steam and the biological environment has been designed and synthesized.

Detecting inflammation in the diabetic mice with a fluorescence lifetime-based probe.

Fluorescence lifetime imaging microscopy (FLIM) is only related to the molecular structure and energy level distribution of the probe, not to the fluorescence intensity. It is an efficient imaging method, because it is not susceptible to interference from the internal environment of biological samples. Diabetes, as a systemic metabolic disease, causes various degrees of inflammation in organs and tissues. As we all know, inflammation of organ and tissue will affect cellular viscosity increases. In this work, a new amphiphilic molecular probe YF-V with a stable structure, good selectivity, fluorescence lifetime response and low cytotoxicity was designed. Under the condition of high viscosity, the rotation of the rotor and the twisting intramolecular charge transfer (TICT) mechanism were inhibited, leading to the extension of the fluorescence lifetime. In the cellular level, YF-V could sensitively detect the dynamic viscosity changes of cells induced by glucose through FLIM. Meanwhile, YF-V is also successfully applied to observe the difference in viscosity between the tissues and organs of diabetic mice and normal mice, and take lead in the detection of organ damage in diabetic mice with different disease durations. This provides an efficient and intuitive method for evaluating organ damage and early diagnosis in diabetes.

Imaging and Detection of Hepatocellular Carcinoma with a Hepatocyte-Specific Fluorescent Probe.

Hepatocellular carcinoma is a highly invasive malignant tumor of the liver, which is the main cause of cancer-related death. The cancerization of hepatocytes may lead to the changes of cell microenvironment, active substances, and enzymes. Viscosity is one of the important parameters of cell microenvironment. Therefore, the study of the change in the viscosity of hepatocytes is very important for the detection and treatment of liver cancer. However, the hepatocyte-specific fluorescent probes which can detect viscosity have not been developed yet. Herein, the first hepatocyte-specific fluorescent probe (HT-V) for viscosity detection was designed and synthesized, which exhibited excellent optical properties for biological imaging studies. By using the unique probe HT-V, compared with the normal liver cells, a significant increase of viscosity in the liver cancer cells was observed in the cell imaging experiment. The organ imaging experiments showed that the probe HT-V could be successfully used to diagnose and image hepatocellular carcinoma in vivo. In addition, in situ imaging revealed that the new probe HT-V can specifically target and image hepatocellular carcinoma in mice. We expected that this powerful tool may provide guidance for the detection and imaging of hepatocellular carcinoma in the future.

LncRNA ELF3-AS1 Promotes Non-Small Cell Lung Cancer Cell Invasion and Migration by Downregulating miR-212.

LncRNA ELF3-AS1 has been characterized as an oncogenic lncRNA in bladder cancer and oral cancer, whereas its role in non-small cell lung cancer (NSCLC) is unknown. In this study, the authors observed that ELF3-AS1 was upregulated in NSCLC tissues in comparison with that in paired nontumor tissues collected from 68 NSCLC patients. High expression levels of ELF3-AS1 predicted the poor survival of NSCLC patients. Expression levels of miR-212 were inversely and significantly correlated with the expression levels of ELF3-AS1 across NSCLC tissue samples. In NSCLC cells, overexpression of ELF3-AS1 led to downregulated miR-212 and increased methylation of miR-212 gene. In addition, overexpression of ELF3-AS1 inhibited the role of miR-212 in suppressing cancer cell invasion and migration. Therefore, ELF3-AS1 is upregulated in NSCLC and promotes cancer cell invasion and migration by downregulating miR-212 through methylation.

The development of a screening model for type 2 diabetes mellitus in community population of Xinjiang Karamay / 中华内分泌代谢杂志

Objective:To develop a nomogram model for screening of type 2 diabetes mellitus in a community population.Methods:From October to December, 2020, 6 028 community residents who participated in the " national health physical examination" in Karamay community with complete physical examination data and met the inclusion and exclusion criteria were selected. The physical examination data included medical history, physical examination, laboratory, and ultrasound reports. Random segmentation sampling was used to divide the population into modeling and validation cohorts, and LASSO regression analysis was used to screen for independent factors associated with diabetes diagnosis. The independent influencing factors were furthor incorporated into the multi-factor logistic regression, and the RMS software package was used to construct the column chart. The area under receiver operating characteristic(ROC) curve was used to measure the differentiation of the model. The calibration curve can directly reflect the calibration degree of the model.Results:In the modeling group, multivariate logistic regression analysis showed that age, gender(female), history of hypertension, history of hyperlipidemia, HbA 1C, urinary microalbumin, homeostasis model assessment for insulin resistance, and triglycerides and glucose index were independently associated with diabetes. OR were 1.053(95% CI 1.038-1.069), 0.681(95% CI 0.512-0.906), 1.802(95% CI 1.227-2.626), 1.789(95% CI 1.303-2.448), 10.973(95% CI 8.318-14.745), 1.002(95% CI 1.001-1.004), 2.914(95% CI 2.248-3.799), and 2.673(95% CI 2.03-3.536), respectively. The areas under ROC curves of the training set and the validation set were 0.945 and 0.955, respectively. The optimal critical value in the ROC curve was 0.178(sensitivity 0.930, specificity 0.839) in the training set and 0.201(sensitivity 0.945, specificity 0.848) in the validation set. Conclusion:The screening model of type 2 diabetes developed in this study has good accuracy, which can be used as a screening tool for high-risk population of type 2 diabetes.

Factors Influencing Sodium Valproate Serum Concentrations in Patients with Epilepsy Based on Logistic Regression Analysis.

BACKGROUND We aimed to explore the risk factors that affect the serum concentration of sodium valproate (VPA-Na) in patients with epilepsy and to provide references for the rationale of the use of VPA-Na. MATERIAL AND METHODS The enzyme-multiplied immunoassay technique was used to determine the serum VPA-NA concentrations of 109 patients, and the results were retrospectively analyzed and summarized. A multivariate logistic regression model was used to analyze substandard serum VPA-Na concentrations. RESULTS Fifty-six patients (51.38%) treated with VPA-Na tablets were within the effective treatment range of 50-100 µg/mL, while 53 patients (48.62%) were out of the treatment range. The results indicated that the standard-reaching rate of serum drug concentration in the juvenile group was higher than that in the adult and elderly groups; the standard-reaching rates of serum drug concentrations in the low-dose group and the intermediate-dose group were lower than that in the high-dose group; and the standard-reaching rate of serum drug concentration in the group receiving carbapenems in combination was lower than that in the non-combination group; all differences were statistically significant. The combination with carbapenems and enzyme inducers was an independent risk factor for VPA-Na serum concentration below the target level in hospitalized patients. CONCLUSIONS To improve clinical efficacy and reduce the occurrence of adverse reactions, there is a need for therapeutic drug monitoring of VPA-Na. Moreover, individual administration should be implemented when VPA-Na tablets are used in the treatment of epilepsy because of the significant fluctuation in VPA-Na blood concentration.

Efficacy and safety of continuous infusion of Rh-endostatin combined with platinum-based chemotherapy for advanced triple-negative breast cancer.

BACKGROUND: This study aimed to prospectively evaluate and investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) combined with platinum-based regimens for advanced triple-negative breast cancer (TNBC) patients. METHODS: This study was a prospective, single-arm, single-center, open-label trial. From January 2017 to August 2019, 21 women aged 18-70 years with histologically confirmed advanced TNBC were enrolled. Rh-endostatin at 30 mg/d was continuously pumped for 7 days and used synchronously with the chemotherapy cycle. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), and toxicity. RESULTS: The median PFS (mPFS) was 8.8 months (95% CI: 7.2-10.4 months), and the median OS was 13.3 months (95% CI: 11.6-15.0 months). The ORR and CBR for the whole population were 47.6% and 52.4%, respectively. Patients sensitive to anthracycline and taxane drugs showed a significantly longer mPFS compared to those who were resistant to anthracycline and taxane drugs (mPFS: 8.8 vs. 5.3 months, P=0.038). For patients who received first- and second-line therapy or beyond, the mPFS was 8.8 and 5.3 months, respectively, with a significant difference (P=0.025). No statistically significant differences in the mPFS between pemetrexed combined with platinum and gemcitabine/taxanes combined with platinum were observed. The most common grade 3-4 hematologic toxicities were neutropenia (14.3%) and anemia (14.3%). One patient (4.8%) experienced febrile neutropenia. No grade 3-4 non-hematologic toxicities were observed, and no treatment-related deaths were reported in this study. CONCLUSIONS: This study revealed that Rh-endostatin might enhance the antitumor effects of platinum-based chemotherapy for advanced TNBC patients with well-tolerated toxicities, which may provide a new basis and novel idea for the treatment of TNBC. However, further investigations and validation of its long-term efficacy and toxicity are warranted in the future.

Correlation between sleep duration and incident diabetes among residents of different ages in Xinjiang region / 中华内分泌代谢杂志

Objective:To explore the correlation between sleep duration and incident diabetes among residents of different ages in Xinjiang region.Methods:A total of 9 541 residents, aged 40 and over in Karamay, Xinjiang were identified by a cluster sampling method. Physical examinations and biochemical test were performed, and the data on sleep duration and lifestyle were obtained using standardized questionnaires. The population was divided into three categories according to sleep duration: insufficient sleep(<6 h), ideal sleep(6-8 h), and long sleep duration(>8 h). They were further divided into 2 subgroups based on age at survey. Those who were younger than 60 years old were defined as the middle-aged group, and the rest as the elderly. Multivariate logistic regression analysis was used to explore the correlation between sleep duration and the risk of diabetes in different age groups.Results:There existed an approximate U-shaped relationship between total sleep duration and fasting blood glucose as well as HbA 1C. Fasting blood glucose and HbA 1C were relatively lower among those with ideal sleep duration. After multivariable adjustment, residents with insufficient sleep revealed a 35% increased risk of diabetes( OR=1.35, 95% CI 1.06-1.71) compared with those with ideal sleep duration. However, the risk of diabetes was not significantly increased in those with long sleep duration( OR=1.04, 95% CI 0.94-1.14). Furthermore, the additive risk of insufficient sleep was only significant in the middle-aged group( OR=1.37, 95% CI 1.02-1.84). Conclusions:Among residents of different ages in Xinjiang region, insufficient sleep is associated with an increased risk of diabetes, which is only significant in the middle-aged group.

Effect of metformin on miRNA expression in type 2 diabetic patients and potential targets / 中华内分泌代谢杂志

Objective:To investigate the effect of metformin on the microRNA (miRNA) expression and screen potential target with network pharmacology analysis in patients with type 2 diabetes.Methods:Fifteen patients with new diagnosed type 2 diabetes admitted to our hospital were selected, who received metformin during hospitalization and after discharge. The expression of serum matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-β1, and myocardial fibrosis related miRNAs were compared before and 6 month after metformin treatment. In addition, gene ontology (GO) and KEGG pathway enrichment analysis were applied to analyze differential expression miRNAs showing statistical significance. Meanwhile, the network figure was established to reflect the target gene messenger RNA (mRNA) corresponding to differentially expressed miRNA.Results:Compared with pre-medication, the serum level of MMP-9 was significantly decreased after treatment ( P<0.05). Besides, the expression of homo sapiens microRNA (hsa-miR)29a-3p, hsa-miR133a-5p, hsa-miR21-5p, hsa-miR30c-5p, and hsa-miR1-3p in patients with type 2 diabetes were dramatically down-regulated by metformin ( P<0.05 or P<0.01). Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in endoplasmic reticulum lumen, synapse, basement membrane and other cell components. The molecular functions such as Rho GTPase binding and participation in extracellular matrix structural constituent were exerted through biological processes such as collagen catabolic process, regulation of short-term neuronal synaptic plasticity, and axon extension, which were mainly enriched in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, tumor necrosis factor (TNF) signaling pathway, and Wnt signaling pathway, etc. The outcome of miRNA-mRNA network analysis demonstrated that there were 230 target genes mRNAs corresponding to differentially expressed miRNA. Conclusion:Metformin could play its role in the treatment of type 2 diabetes by down regulating the expression of miRNA, participating in the transduction of related cellular signaling pathways, regulating chromatin, nucleic acid binding, and enzyme activities.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China / 中华医学杂志(英文版)

BACKGROUND@#There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.@*METHODS@#From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.@*RESULTS@#Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).@*CONCLUSIONS@#Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Mesenchymal Stem Cell-Secreted Exosome Promotes Chemoresistance in Breast Cancer via Enhancing miR-21-5p-Mediated S100A6 Expression.

Emerging evidence has shown the role of mesenchymal stem cell-derived exosome (MSC-exo) in inducing resistance of cancer cells to chemotherapy. However, it remains unclear whether the change of MSC-exo in response to chemotherapy also contributes to chemoresistance. In this study, we investigated the effect of a standard-of-care chemotherapeutic agent, doxorubicin (Dox), on MSC-exo and its contribution to the development of Dox resistance in breast cancer cells (BCs). We found that the exosome secreted by Dox-treated MSCs (Dt-MSC-exo) induced a higher degree of Dox resistance in BCs when compared with non-treated MSC-exo. By analysis of the MSC-exo-induced transcriptome change in BCs, we identified S100A6, a chemoresistant gene, as a top-ranked gene induced by MSC-exo in BCs, which was further enhanced by Dt-MSC-exo. Furthermore, we found that Dox induced the expression of miR-21-5p in MSCs and MSC-exo, which was required for the expression of S100A6 in BCs. Importantly, silencing of miR-21-5p expression in MSCs and MSC-exo abolished the resistance of BCs to Dox, indicating an exosomal miR-21-5p-regulated S100A6 in chemoresistance. Our study thus uncovered a novel mechanistic insight into the role of MSC-secreted exosome in the development of chemoresistance in the tumor microenvironment.

Leptin promotes bone metastasis of breast cancer by activating the SDF-1/CXCR4 axis.

Obesity is associated with an increased risk of tumorigenesis, and increased leptin levels can promote tumor metastasis. However, the effects of leptin on bone metastasis in breast cancer are not fully understood. Here, we examined leptin receptor expression and bone metastasis in tissue samples from 96 breast cancer patients. In addition, we investigated the effects of leptin on the metastatic capacity of breast cancer cells invitro using a transwell assays. The results indicated that higher leptin receptor levels in breast cancer cells are associated with increased incidence of bone metastasis in breast cancer patients. Additionally, leptin promoted migration and invasion of breast cancer cells. The SDF-1/CXCR4 axis activated by leptin also promoted bone metastasis of breast cancer. Finally, increased CXCR4 expression was accompanied by high leptin receptor expression in bone metastatic tissues from breast cancer patients. These results indicate that leptin induces bone metastasis of breast cancer by activating the SDF-1/CXCR4 axis.

Baicalein suppresses vasculogenic mimicry through inhibiting RhoA/ROCK expression in lung cancer A549 cell line.

Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.

A validated LC-MS/MS method for the quantification of capivasertib in dog plasma: Application to its pharmacokinetics study.

In this study, a simple and reliable liquid chromatography tandem mass spectrometric method was first developed for the determination of capivasertib in dog plasma with ipatasertib as internal standard. The plasma samples were deproteinated using acetonitrile. An Acquity BEH C18 column (1.7 µm, 2.1 × 50 mm) maintained at 40°C was used for chromatographical separation, with water containing 0.1% formic acid and acetonitrile as mobile phase. Multiple reaction monitoring transitions were m/z 429.2 > 135.1 for capivasertib and m/z 458.2 > 387.2 for ipatasertib, respectively. Excellent linearity was achieved in the concentration range of 1-1,000 ng/ml with a correlation coefficient of >0.9981. The lower limit of quantification was 1 ng/ml. The extraction recovery of capivasertib from dog plasma was >85.81% and no significant matrix effect was found. The intra- and inter-day precision was <9.58% and the accuracy ranged from -10.60% to 12.50%. The validated method was further applied to the pharmacokinetic study of capivasertib in dog plasma after single oral (5 mg/kg) and intravenous (1 mg/kg) administrations. The results revealed that capivasertib was rapidly absorbed into plasma with good bioavailability (47.04%) and low clearance.

Long Noncoding RNA SNHG10 Sponges miR-543 to Upregulate Tumor Suppressive SIRT1 in Nonsmall Cell Lung Cancer.

Background: Long noncoding RNA SNHG10 has been reported to promote the development of liver cancer. While by analyzing The Cancer Genome Atlas (TCGA) dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC). This study aimed to investigate the roles of SNHG10 in NSCLC. Materials and Methods: This study included 60 pairs of NSCLC and nontumor tissue samples collected from 60 NSCLC patients (males and females, 39-66 years, 50.9 ± 5.5 years). Gene expression was detected by quantitative polymerase chain reaction and western blot. Overexpression experiments were used to analyze gene interactions. Effects of cell transfections on cell proliferation were analyzed by performing CCK-8 cell proliferation assays. Results: We confirmed the downregulation of SNHG10 in NSCLC. In addition, low expression level of SNHG10 predicted the poor survival of NSCLC patients. SNHG10 can directly interact with miR-543, while overexpression of miR-543 failed to downregulate SNHG10. However, SNHG10 overexpression led to upregulation of sirtuin 1 (SIRT1), a downstream target of miR-543. Cell proliferation assay showed that SNHG10 and SIRT1 overexpression led to the decreased proliferation rate of NSCLC cells. In contrast, miR-543 over-expression played an opposite role and reduced the effects of SNHG10 and SIRT1 overexpression. Conclusions: In conclusion, SNHG10 sponges miR-543 to upregulate tumor suppressive SIRT1 in NSCLC to suppress cell proliferation.

Aspirin alleviates hepatic fibrosis by suppressing hepatic stellate cells activation via the TLR4/NF-κB pathway.

Hepatic fibrosis arises from a sustained wound-healing response to chronic liver injury. Because the occurrence and development of hepatic fibrosis is always associated with chronic inflammation, controlling inflammation within the liver may be an effective means of controlling the development and progression of hepatic fibrosis. Aspirin is a non-steroidal anti-inflammatory drug used to relieve both inflammatory symptoms and pain. The results of our study showed that aspirin significantly attenuated hepatic inflammation and fibrosis. Aspirin effectively inhibited the activation and proliferation of hepatic stellate cells (HSCs), which led to downregulation of inflammatory factors, including IL-6 and TNF-α in those cells. Aspirin also downregulated expression of Toll-like receptor-4 (TLR4) on HSCs, as well as its downstream mediators, MyD88 and NF-κB. The results of our study demonstrate aspirin's potential to inhibit the development of hepatic fibrosis and the molecular mechanism by which it acts. They suggest aspirin may be an effective therapeutic agent for the treatment of hepatic fibrosis.

Outcomes of 33 patients with anaplastic large cell lymphoma treated after hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK(+) and 9 ones (27.3%) ALK(-). Of them, 25 patients (19 ALK(+) and 6 ALK(-)) underwent auto-HSCT and 8 cases (5 ALK(+) and 3ALK(-)) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion: ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.