Atorvastatin Plus Low-Dose Dexamethasone May Be Effective for Leukemia-Related Chronic Subdural Hematoma but Not for Leukemia Encephalopathy: A Report of Three Cases.

We are not aware of any reports regarding conservative treatment for leukemia-related chronic subdural hematoma (CSDH). We report our experience with 3 men who were admitted with subdural masses and abnormal leukocyte counts. In two patients, leukemia and CSDH were confirmed on the basis of medical records, mild head trauma, and neuroimaging features. Both patients experienced reduced CSDH and neurological symptoms after receiving atorvastatin (20 mg/day) plus low-dose dexamethasone. However, this combined conservative treatment was ineffective in the third patient, who was diagnosed as having leukemia and showed an increased hematoma volume after two weeks of therapy. Magnetic resonance imaging findings suggested dural metastasis, which prompted a switch from statin-based conservative treatment to chemotherapy. Complete remission of the leukemia and resolution of the subdural mass were observed after chemotherapy, which supported a diagnosis of leukemia encephalopathy. The 5-month follow-ups did not reveal CSDH relapse in all 3 cases. Thus, atorvastatin-based conservative treatment may be effective for leukemia-related CSDH but not for leukemia encephalopathy.

Self-assembly of photosensitive and radiotherapeutic peptide for combined photodynamic-radio cancer therapy with intracellular delivery of miRNA-139-5p.

BACKGROUND: A significant challenge in cancer therapy is to maximize the therapeutic efficacy and minimize the side effects. In the past decade, a lot of nanoparticles have been used as the carriers for efficient drug delivery. METHODS AND RESULTS: This study was to prepare R9 modified with 125I-labeled cRGD and ce6 which self-assembled with miR-139-5p to form nanoparticles (Ce6-R9-125I-RGD-MNPs), and to further take advantage of the enhanced permeability and retention (EPR) effect of radiolabeled nanoparticles to realize the integration of tumor diagnosis and treatment. We successfully synthesized and represented it, saline and serum stability experiments demonstrating good stability. Moreover, Ce6-R9-125I-RGD-MNPs showed superior tumor targeting and the effect of combined photodynamic therapy (PDT) and radiotherapy treatment in vivo and vitro. CONCLUSION: The pathological results further confirmed that the therapeutic doses of Ce6-R9-125I-RGD-MNPs cause pathological changes of tumor tissues while showing minimal toxicity to normal tissues.

Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1.

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro. Our research fills a gap which has existed in the study of inflammatory stress about the V-ATPase subunit ATP6V0D2 in liver macrophages. We first found that the expression of specific ATP6V0D2 in liver macrophages was upregulated with the induction of inflammatory cascade after liver IR surgery, and knockdown of ATP6V0D2 resulted in increased secretion of proinflammatory factors and chemokines, which enhanced activation of NLRP3 and aggravation of liver injury. Further studies found that the exacerbated activation of NLRP3 was related to the autophagic flux regulated by ATP6V0D2. Knocking down ATP6V0D2 impaired the formation of autophagolysosome and aggravated liver IR injury through nonspecific V-ATPase activation independent of V-ATPase-Notchl-Hesl signal axis. In general, we illustrated that the expression of ATP6V0D2 in liver macrophages was upregulated after liver IR, and by gradually promoting the formation of autophagolysosomes to increase autophagy flux to limit the activation of liver inflammation, this regulation is independent of the Notch1-Hes1 signal axis.

Mechanisms of Fritillariae Thunbergii Flos in lung cancer treatment from a systems pharmacology perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Thunbergii Flos (FTF) included in the Chinese Pharmacopoeia (1977 Edition) is a Chinese medicinal herb traditionally used to treat bronchitis. In recent years, it has been applied in the treatment of lung cancer. However, the molecular mechanism remains largely unknown. METHODS: The screening of bioactive compounds, acquisition of drug targets, network construction, and experimental validation in vivo were combined to explored the mechanism of FTF in the treatment of lung carcinoma with regards to systems pharmacology. RESULTS: The network Lung Cancer Pathway consisted of 114 nodes (44 compounds and 70 potential targets) and 361 edges, as well as modules that included inflammatory response, angiogenesis, negative regulation of the apoptotic process, and positive regulation of cell proliferation and migration. It was examined by conducting experiments that involved the administration of ethanol-based extracts of FTF in Lewis lung carcinoma mice. The extracts exerted excellent anti-lung cancer effects in vivo by significantly inhibiting tumor proliferation, thereby extending the survival period of tumor-bearing mice. Moreover, FTF induced the downregulation of PIK3CG, Bcl-2, eNOS, VEGF, p-STAT3, and STAT3 genes in tumor-bearing mice. CONCLUSIONS: The findings of the present study verify the therapeutic effects and mechanism of FTF on lung cancer and provide a theoretical basis to support the comprehensive utilization of FTF resources.

BLACAT1 predicts poor prognosis and serves as oncogenic lncRNA in small-cell lung cancer.

Bladder cancer-associated transcript 1 (BLACAT1) is a novel identified long noncoding RNA (lncRNA) in bladder cancer, and has been suggested to function as an oncogenic lncRNA in several types of human cancer. However, its involvement in the progression of small-cell lung cancer (SCLC) remained unknown. The aim of our study was to investigate the clinical value and biological function in SCLC. In our results, BLACAT1 expression was increased in SCLC tissues and cell lines compared with paired adjacent normal tissues and bronchial epithelial cell lines, respectively. In addition, BLACAT1 high-expression was obviously associated with advanced clinical stage, large tumor size, more lymph node metastasis, present distant metastasis, and poor prognosis. Furthermore, multivariate analysis indicated that high-expression of BLACAT1 acted as an independent poor prognostic factor for overall survival in SCLC cases. The loss-of-function studies suggested that of BLACAT1 suppressed SCLC cell proliferation, migration, and invasion, and induced G0/G1 phase arrest. In conclusion, BLACAT1 is associated with the malignant status and prognosis in patients with SCLC, and functions as an oncogenic lncRNA in regulating cell proliferation and motility, suggesting BLACAT1 may act as a potential target for SCLC prevention and treatment.

Metabolic profiling investigation of Fritillaria thunbergii Miq. by gas chromatography-mass spectrometry.

Thunberg fritillary bulb (the dry bulbs of Fritillaria thunbergii Miq.), a traditional Chinese Medicine, is widely applied as an expectorant and antitussive. In this investigation, the primary metabolites of bulbs, flowers, leaves, and stems of F. thunbergii were analyzed by gas chromatography-mass spectrometry. Principal component analysis, partial least squares-discriminate analysis, orthogonal projection to latent structures-discriminate analysis, and heat map analysis showed that there were dissimilar metabolites, and a negative correlation between amino acids and saccharides in different analytes. Furthermore, carbodiimide, tryptophan, glucose-6-phosphate, xylose, 2-piperidinecarboxylic acid, monoamidomalonic acid, phenylalanine, and histidine were found to play an important role in the plant metabolism net of F. thunbergii.

Clinical experience with radio-, chemo- and hyperthermotherapy combined trimodality on locally advanced esophageal cancer.

Esophageal cancer is a highly malignant and lethal disease with a low 5-year survival rate. Therefore, an effective treatment modality is required. To investigate the treatment efficacy and toxicity of radio-, chemo- and hyper-thermotherapy combined trimodality on locally advanced esophageal cancer, the medical records of 78 patients with pathologically confirmed esophageal cancer treated with chemoradiotherapy plus hyperthemia at our institution were retrospectively investigated and the 3-year outcome was carefully assessed. All 78 patients received intensity-modulated radiation therapy at a total dose of 60-66 Gy, in a conventional schedule of 1.8-2.1 Gy/fraction, 5 fractions/week. They also received 4-6 courses of chemotherapy, consisting of 450 mg/m2 5-fluorouracil for 1-5 days and 25 mg/m2 cisplatin for 1-5 days, in addition to 6-12 sessions of hyperthermia, performed twice a week. Out of the 78 cases, complete remission of the primary tumor was observed in 31 (39.7%), partial remission in 44 (56.4%) and no change in 3 (3.9%) cases. The treatment response rate was 96.1%. The overall survival (OS) rate at 1, 2 and 3 years was 67.9, 41.0 and 33.3%, respectively. No significant difference in adverse effects was observed between this treatment regimen and other similar studies. Our preliminary results demonstrated that the chemo-, radio- and hyperthermotherapy combined trimodality exhibited excellent short-term clinical outcomes as regards tumor response rate and a sound long-term OS, with endurable adverse events. This trimodal treatment requires further investigation to establish its beneficial role in the treatment of patients with locally advanced esophageal cancer.

[Determination of residual organic solvents in Panax notoginseng extracts by capillary gas chromatography with headspace sampling].

OBJECTIVE: To develop a headspace gas chromatography method for the determination of residual organic solvents in Panax notoginseng extracts. METHODS: The samples were injected into HP-INNOWAX capillary column by headspace sampler and analyzed with FID detector using standard addition method. RESULTS: There was a good linearity in the experimental concentration (r=0.9932-0.9999). The rate of recovery was in the rang of 81.74%-111.2%. The numbers of theoretical plates were more than 15000 and the resolutions between the adjacent peaks were more than 2. The RSD of precision and accuracy were both less than 10 %. CONCLUSION: The method is simple,accurate and sensitive with good reproducibility, which can be used for the determination of the residual organic solvents in Panax notoginseng extracts.

Real-time TaqMan polymerase chain reaction assays for quantitative detection and differentiation of Ureaplasma urealyticum and Ureaplasma parvum.

Evidence has been presented that the species currently known as Ureaplasma urealyticum should be separated into 2 species-Ureaplasma parvum (previously, U. urealyticum biovar 1) and U. urealyticum (previously, U. urealyticum biovar 2). Differentiation and quantification of U. parvum and U. urealyticum can provide important information of the epidemiology of Ureaplasma infections. We developed 2 real-time TaqMan polymerase chain reaction (PCR) assays that would allow rapid, specific, sensitive, quantitative detection and convenient differentiation of U. parvum and U. urealyticum. One hundred twenty-eight clinical specimens were studied and compared with results obtained by culture methods and conventional PCR. The positive rate of real-time TaqMan PCR (59.4%, 76 of 128) was higher than that of culture methods (42.2%, 54 of 128) and conventional PCR (50%, 64 of 128). Of 76 positive specimens, 86.8% (66) contained U. parvum only, 10.5% (8) contained U. urealyticum only, and 2.6% (2) contained both. The copy numbers of 11 positive specimens were in the range of 10(1) to 10(3) copies per reaction mixture, 18 in the range of 10(3) to 10(5), and 47 in the range of 10(5) to 10(8). In the future, quantitative detection and convenient differentiation of real-time TaqMan PCR assays will assist in the study of the pathogenesis and epidemiology of Ureaplasma infections.