Swimming ability of Schizothoracinae fishes in Yarlung Zangbo River of China.

The Yarlung Zangbo River is a river with abundant hydropower resources but fragile biodiversity in China. As an important benchmark for both research and ecological management, there is still a lack of knowledge about the swimming ability of fishes in the Yarlung Zangbo River. The induced flow velocity (Uind), critical swimming speed (Ucrit), and burst swimming speed (Uburst) of five Schizothoracinae species were tested in this study. Relative swimming ability related to body length and body shape was calculated. The results indicated that the average absolute swimming speeds (Uind-a, Ucrit-a, and Uburst-a) of all the experimental fish were 10.20 ± 0.01, 57.58 ± 3.28, and 69.54 ± 2.94 cm/s, respectively, and the corresponding relative Uind, Ucrit, and Uburst related to body length (Uind-l, Ucrit-l, Uburst-l) were 1.15 ± 0.07, 5.04 ± 0.26, and 7.23 ± 0.28 BL/s, respectively. Moreover, relative Uind, Ucrit, and Uburst related to body shape (Uind-s, Ucrit-s, and Uburst-s) were 0.80 ± 0.13, 2.49 ± 0.51, and 4.32 ± 0.57 cm-2/s, respectively. No significantly differences in relative swimming speeds existed among five species. Only Oxygymnocypris stewartii was significantly weaker in Uburst-s than Schizothorax o'connori. The body shape showed a stronger relationship with swimming speed than the body length did. Schizothoracinae fish in the Yarlung Zangbo River basin are less sensitive to the water flow and performed weaker Ucrit and Uburst compared to those in the Yangtze River basin, indicating that Schizothoracinae fish in the Yarlung Zangbo River may be more susceptible to threats from environmental changes. The paper enriched the research on the swimming ability of Schizothoracinae fishes and provided efficient data for the fish conservation in the Yarlung Zangbo River.

Prediction of Survival Rate and Chemotherapy Effect by an Immune Score Model in Colorectal Cancer.

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths. Immune cells in the tumor microenvironment play an important role in the development of tumors. In this study, CIBERSORT was used to estimate the subset of the immune cells using bulk gene expression data (i.e., TCGA, GEO, and cBioPortal databases). 1,087 samples were included in the analysis. The results revealed that among the 22 immune cell subsets that were evaluated, resting and activated NK cells, macrophage M1 and M2, and resting mast cells are associated with significant improvements in patient survival of colorectal cancer. The 15-year survival rates for the training cohort showed 49.1% and 32.5%, respectively, for the low- and high-risk groups. Likewise, the validation and entire cohorts showed 77.3% versus 47.2% and 65.3% versus 46.5%, respectively, for the low- and high-risk groups. Also, the prognostic immune score in predicting the chemotherapy effects showed that the low-risk group had a better survival superiority over the high-risk group, whether patients received chemotherapy or not. The gene set enrichment analysis showed that the low-risk group was highly enriched in pathways or processes related to immune response. The immune checkpoint assessment revealed significantly higher mRNA expressions of CTLA4 in the lower risk group than in the higher risk group. Altogether, this study offers information that could improve the prognosis of colorectal cancer.

Clinical Efficacy Analysis of the Combination of the Laparoscope and Preoperative or Intraoperative Duodenoscope in the Treatment of Cholecystolithiasis with Choledocholithiasis: A Retrospective Study.

Aim: This study aims to analyze the efficacy and safety of the combination of laparoscope and preoperative (PODL) or intraoperative (IODL) duodenoscope in the treatment of cholecystolithiasis with choledocholithiasis. Materials and Methods: From January 2015 to February 2017, 51 patients with cholecystolithiasis and choledocholithiasis, who were treated with the PODL (n = 29) or IODL (n = 22), were reviewed retrospectively. The efficacy and safety were evaluated and compared between these two groups. Results: The success rates were 100% in IODL group and 96.6% in PODL group. There was no statistical significance in the difference of stone clearance rate and residual stone rate between two groups (P > .05). There were no significant differences in complications, like aspiration, gastrointestinal perforation, and acute cholangitis between two groups (P > .05). IODL significantly decreased numeric rating scale (NRS) scoring, reduced surgery cost and shortened hospitalization time compared to that of PODL group (P < .05). No cholangitis, reoccurrence of stones or biliary obstruction occurred in all 51 patients. Conclusion: In this retrospective study, IODL was found superior to PODL. And the IODL can significantly decrease NRS scoring, reduce surgery cost and shorten hospitalization time.

Substance P Mediated DGLs Complexing with DACHPt for Targeting Therapy of Glioma.

Currently, glioblastoma (glioma) is described as the deadliest brain tumor for its invasive natural with exceeding difficulty in surgical excision. Blood-brain barrier (BBB) can restrict the penetration of most therapeutic reagents including platinum (Pt)-based drugs-the most widely used reagents in clinical trials for their revolutionized cancer chemotherapy against a broad range of tumors. Nanomedicine represents a promising strategy for the intravenous delivery of Pt-based drugs into the brain. In this research, with the aim of malignant glioma treatment by Pt-based drugs, a novel nano drug carrier was developed: dendrigraft poly-L-lysines (DGLs) was PEGylated, linked with diethylenetriaminpentaacetic acid (DTPA) to complex (1,2-diaminocyclohexane)platinum(II) (DACHPt), and modified with Substance P (SP) as a BBB/glioma dual-targeting moiety. The preparation and characterization of the platform were exhibited in detail. The increased targeting capability and antitumor effect was found both in vitro and in vivo. The well-defined chemical composition, rigorously nanoscaled size and the first attempt of using SP as a BBB/glioma dual-targeting group were highlighted. The combined results suggest this strategy may serve as novel formulation for Pt-based drugs with the aim of clinical glioma treatment.

Evidence of elemene injection combined radiotherapy in lung cancer treatment among patients with brain metastases: A systematic review and meta-analysis.

BACKGROUND: This review evaluates the effectiveness and safety of elemene injection combined radiotherapy in the treatment of lung cancer with brain metastases. METHODS: A systematic literature research was conducted from EMBASE, Cochrane Library, PubMed, Chinese biomedical database, Chinese scientific journal database, China knowledge resource integrated database, and WanFang Database from established to July 2016 without language restriction. The Cochrane Collaboration tool was used to evaluate the risk of bias. All statistical analyses were conducted with STATA (version 14.0) and RevMan (version 5.3). RESULTS: Eleven randomized controlled trials (765 patients) were included for determining the effectiveness and safety of elemene combined with radiotherapy in the treatment of lung cancer with brain metastases. Objective response rate (ORR) [odds ratio (OR) = 2.89, 95% confidence interval (95% CI) 2.04-4.08, P < .00001] and symptoms (OR = 4.06, 95% CI 2.00-8.25, P = .0001) improved more in the elemene-based combination treatment group than in the radiotherapy-alone control group. The Karnofsky Performance Status (KPS) score was used to measure patients' improvement rate. The patients who were treated with elemene-based combination with radiotherapy were higher than those patients who were treated with radiotherapy alone (OR = 3.51, 95% CI 2.20-5.61, P < .00001]. The incidence of bone marrow suppression (OR = 0.27, 95% CI 0.11-0.68, P = .006) and leukopenia (OR = 0.23, 95% CI 0.12-0.46, P < .00001) decreased in the elemene-based combination treatment group by radiotherapy significantly. CONCLUSIONS: The elemene injection combined radiotherapy in the treatment of lung cancer with brain metastases appears to improve the treatment response rate and alleviated symptoms. The combined treatment has showed positive impact to reduce adverse reactions and improve quality of life.

Dual Functional Peptide-Driven Nanoparticles for Highly Efficient Glioma-Targeting and Drug Codelivery.

Compared with peripheral tumors, glioma is very difficult to treat, not only because it has general features of tumor but also because the therapy has been restricted by the brain-blood barrier (BBB). The two main features of tumor growth are angiogenesis and proliferation of tumor cells. RNA interference (RNAi) can downregulate VEGF overexpression to inhibit tumor neovascularization. Meanwhile, doxorubicin (DOX) has been used for cytotoxic chemotherapy to kill tumor cells. Thus, combining RNAi and chemotherapy has been regarded as a potential strategy for cancer treatment. However, the BBB limits the shVEGF-DOX codelivery system to direct into glioma. Here, a smart drug delivery system modified with a dual functional peptide was established, which could target to transferrin receptor (TfR) overexpressing on both the BBB and glioma. It showed that the dual-targeting delivery system had high tumor targeting efficiency in vitro and in vivo.

Development of chitosan nanoparticles as drug delivery system for a prototype capsid inhibitor.

Oral delivery of biopharmaceutics drug disposition classification system (BDDCS) Class II or IV drugs with poor aqueous solubility and poor enzymatic and/or metabolic stability is very challenging. Bay41-4109, a member of the heteroaryldihydropyrimidine (HAP) family, inhibits HBV replication by destabilizing capsid assembly. It pertains to class II of the BDDCS which has a practically insoluble solubility which is 38 µg/mL (LYSA) and the oral delivery resulted in low bioavailability. The purpose of the current research work was to develop and evaluate Bay41-4109 loaded chitosan nanoparticles to increase the solubility and bioavailability for treatment of HBV. The Bay41-4109 nanoparticles were prepared by gelation of chitosan with tripolyphosphate (TPP) through ionic cross-linking. A three-factor three-level central composite design (CCD) was introduced to perform the experiments. A quadratic polynomial model was generated to predict and evaluate the independent variables with respect to the dependent variables. Bay41-4109 was encapsulated in the chitosan nanoparticles were demonstrated by PLM, FTIR, DSC, XRD and TEM etc. The in vivo results suggest that Bay41-4109 nanoparticles have better bioavailability and would be a promising approach for oral delivery of Bay41-4109 for the treatment of HBV.

Choline Derivate-Modified Doxorubicin Loaded Micelle for Glioma Therapy.

Ligand-mediated polymeric micelles have enormous potential for improving the efficacy of glioma therapy. Linear-dendritic drug-polymer conjugates composed of doxorubicin (DOX) and polyethylene glycol (PEG) were synthesized with or without modification of choline derivate (CD). The resulting MeO-PEG-DOX8 and CD-PEG-DOX8 could self-assemble into polymeric micelles with a nanosized diameter around 30 nm and a high drug loading content up to 40.6 and 32.3%, respectively. The optimized formulation 20% CD-PEG-DOX8 micelles had superior cellular uptake and antitumor activity against MeO-PEG-DOX8 micelles. The subcellular distribution using confocal study revealed that 20% CD-PEG-DOX8 micelles preferentially accumulated in the mitochondria. Pharmacokinetic study showed area under the plasma concentration-time curve (AUC0-t) and Cmax for 20% CD-PEG-DOX8 micelles and DOX solution were 1336.58 ± 179.43 mg/L·h, 96.35 ± 3.32 mg/L and 1.40 ± 0.19 mg/L·h, 1.15 ± 0.25 mg/L, respectively. Biodistribution study showed the DOX concentration of 20% CD-PEG-DOX8 micelles treated group at 48 h was 2.37-fold higher than that of MeO-PEG-DOX8 micelles treated group at 48 h and was 24 fold-higher than that of DOX solution treated group at 24 h. CD-PEG-DOX8 micelles (20%) were well tolerated with reduced cardiotoxicity, as evaluated in the body weight change and HE staining studies, while they induced most significant antitumor activity with longest media survival time in an orthotopic mouse model of U87-luci glioblastoma model as displayed in the bioluminescence imaging and survival curve studies. Our findings consequently indicated that 20% CD-PEG-DOX8 micelles are promising drug delivery system for glioma chemotherapy.

Single-component self-assembled RNAi nanoparticles functionalized with tumor-targeting iNGR delivering abundant siRNA for efficient glioma therapy.

Existing limitations of common RNA interference (RNAi) oncotherapy severely compromised their therapeutic effects. In this study, a novel glioma-targeting RNAi system was developed. Single-component RNAi nanospheres were tactfully self-assembled in vitro, combining the carrier and cargo as a whole. An artificially synthesized polycation (pOEI) with redox-sensitive disulfides in structure condensed the RNAi nanospheres into more compacted nanoparticles. Then a novelly designed tumor-homing and penetrating cyclopeptide iNGR was further modified on the surface. iNGR modified RNAi nanoparticles demonstrated significantly enhanced accumulation in glioma site, remaining stable in circulation until the release of naked RNAi nanospheres were triggered off by the paranormal concentration of glutathione within glioma cells. Naked RNAi nanospheres were digested into abudant siRNA afterwards. Remarkable luciferase gene down-regulations have confirmed their outstanding RNAi effects. With specific design of sequences, the iNGR modified RNAi nanoparticles were supposed to be of great potential in safe and efficient glioma therapy in future.

Cell microenvironment-controlled antitumor drug releasing-nanomicelles for GLUT1-targeting hepatocellular carcinoma therapy.

In clinical therapy, the poor prognosis of hepatocellular carcinoma (HCC) is mainly attributed to the failure of chemotherapeutical agents to accumulate in tumor as well as their serious systemic toxicity. In this work, we developed actively tumor-targeting trilayer micelles with microenvironment-sensitive cross-links as a novel nanocarrier for HCC therapy. These micelles comprised biodegradable PEG-pLys-pPhe polymers, in which pLys could react with a disulfide-containing agent to form redox-responsive cross-links. In vitro drug release and pharmacokinetics studies showed that these cross-links were stable in physiological condition whereas cleaved once internalized into cells due to the high level of glutathione, resulting in facilitated intracellular doxorubicin release. In addition, dehydroascorbic acid (DHAA) was decorated on the surface of micelles for specific recognition of tumor cells via GLUT1, a member of glucose transporter family overexpressed on hepatocarcinoma cells. Moreover, DHAA exhibited a "one-way" continuous accumulation within tumor cells. Cellular uptake and in vivo imaging studies proved that these micelles had remarkable targeting property toward hepatocarcinoma cells and tumor. Enhanced anti-HCC efficacy of the micelles was also confirmed both in vitro and in vivo. Therefore, this micellar system may be a potential platform of chemotherapeutics delivery for HCC therapy.

Linear-dendritic copolymer composed of polyethylene glycol and all-trans-retinoic acid as drug delivery platform for paclitaxel against breast cancer.

A new linear-dendritic copolymer composed of poly(ethylene glycol) (PEG) and all-trans-retinoic acid (ATRA) was synthesized as the anticancer drug delivery platform (PEG-G3-RA8). It can self-assemble into core-shell micelles with a low critical micelle concentration (CMC) at 3.48 mg/L. Paclitaxel (PTX) was encapsulated into PEG-G3-RA8 to form PEG-G3-RA8/PTX micelles for breast cancer treatment. The optimized formulation had high drug loading efficacy (20% w/w of drug copolymer ratio), nanosized diameter (27.6 nm), and narrow distribution (PDI = 0.103). Compared with Taxol, PEG-G3-RA8/PTX remained highly stable in the serum-containing cell medium and exhibited 4-fold higher cellular uptake. Besides, near-infrared fluorescence (NIR) optical imaging results indicated that fluorescent probe loaded micelle had a preferential accumulation in breast tumors. Pharmacokinetics and biodistribution studies (10 mg/kg) showed the area under the plasma concentration-time curve (AUC0-∞) and mean residence time (MRT0-∞) for PEG-G3-RA8/PTX and Taxol were 12.006 ± 0.605 mg/L h, 2.264 ± 0.041 h and 15.966 ± 1.614 mg/L h, 1.726 ± 0.097 h, respectively. The tumor accumulation of PEG-G3-RA8/PTX group was 1.89-fold higher than that of Taxol group 24 h postinjection. With the advantages like efficient cellular uptake and preferential tumor accumulation, PEG-G3-RA8/PTX showed superior therapeutic efficacy on MCF-7 tumor bearing mice compared to Taxol.