Integrative Effects of Transcutaneous Electrical Acustimulation and Autonomic-Endocrine Mechanisms on Postprocedural Recovery in Patients With Endoscopic Retrograde Cholangio-Pancreatography.

OBJECTIVES: This study aimed to investigate the integrative effects and mechanisms of transcutaneous electrical acustimulation (TEA) on postprocedural recovery from endoscopic retrograde cholangio-pancreatography (ERCP). MATERIALS AND METHODS: A total of 86 patients for elective ERCP were randomly ordered to receive TEA (n = 43) at acupoints PC6 and ST36 or Sham-TEA (n = 43) at sham points from 24 hours before ERCP (pre-ERCP) to 24 hours after ERCP (PE24). Scores of gastrointestinal (GI) motility-related symptoms and abdominal pain, gastric slow waves, and autonomic functions were recorded through the spectral analysis of heart rate variability; meanwhile, circulatory levels of inflammation cytokines of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 and GI hormones of motilin, ghrelin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were assessed by enzyme-linked immunosorbent assay. RESULTS: 1) TEA, but not Sham-TEA, decreased the post-ERCP GI motility-related symptom score (2.4 ± 2.6 vs 7.9 ± 4.6, p < 0.001) and abdominal pain score (0.5 ± 0.7 vs 4.1 ± 2.7, p < 0.001) at PE24, and decreased the post-ERCP hospital day by 20.0% (p ＜0.05 vs Sham-TEA); 2) TEA improved the average gastric percentage of normal slow waves and dominant frequency by 34.6% and 33.3% at PE24, respectively (both p < 0.001 vs Sham-TEA); 3) TEA, but not Sham-TEA, reversed the ERCP-induced increase of TNF-α but not IL-10 at PE24, reflected as a significantly lower level of TNF-α in the TEA group than in the Sham-TEA group (1.6 ± 0.5 pg/mL vs 2.1 ± 0.9 pg/mL, p ＜ 0.01); 4) compared with Sham-TEA, TEA increased vagal activity by 37.5% (p ＜ 0.001); and 5) TEA caused a significantly higher plasma level of ghrelin (1.5 ± 0.8 ng/ml vs 1.1 ± 0.7 ng/ml, p ＜ 0.05) but not motilin, VIP, or CCK than did Sham-TEA at PE24. CONCLUSION: TEA at PC6 and ST36 accelerates the post-ERCP recovery, reflected as the improvement in GI motility and amelioration of abdominal pain, and suppression of the inflammatory cytokine TNF-α may mediate through both autonomic and ghrelin-related mechanisms.

The efficacy of RGD modified liposomes loaded with vinorelbine plus tetrandrine in treating resistant brain glioma.

Brain glioma is one of the most common and devastating intracranial malignancies with a high mortality. Chemotherapy for brain glioma is not ideal due to blood brain barrier (BBB) and multidrug resistance (MDR). The objectives of the present study were to develop a kind of RGD (Arg-Gly-Asp) tripeptide modified vinorelbine plus tetrandrine liposomes to achieve BBB transportation, MDR reversion and glioma cell targeting simultaneously. The studies were performed on glioma cells, resistant glioma cells and glioma-bearing mice. Results showed that the constructed liposomes with suitable physicochemical properties could significantly enhance the transport across BBB, obviously accumulate in glioma cells, and exhibit evident capabilities in diminishing brain glioma in mice. Action mechanism studies indicated that the enhanced anticancer efficacy could be attribute to the follows: prolonged elimination half-life (7.093 ± 1.311 h); increased AUC0-24 h (28.92 ± 2.66 mg/L*h); transporting across BBB; enhanced cellular uptake; down-regulation on P-gp (0.49 ± 0.06 fold); inducing apoptosis via activating caspase 8, 9, and 3 (2.40 ± 0.22, 3.57 ± 0.29, and 4.33 ± 0.30 folds, respectively). In conclusion, the RGD modified vinorelbine plus tetrandrine liposomes may offer a promising therapeutic strategy for treatment of brain glioma.

Efficacy in Treating Lung Metastasis of Invasive Breast Cancer with Functional Vincristine Plus Dasatinib Liposomes.

BACKGROUND: The metastasis of breast cancer is the leading cause of death, while lung metastasis is a major clinical phenomenon in patients with invasive breast cancer. The current treatment option comprising surgery, radiation, and standard chemotherapy cannot achieve a satisfactory effect on the treatment of lung metastasis of breast cancer. In this study, we report the potential of preventing lung metastasis of invasive breast cancer using the newly developed functional vincristine plus dasatinib liposomes. METHODS: The investigations were performed on invasive breast cancer MDA-MB-231 cells in vitro and in lung metastatic model of invasive breast cancer MDA-MB-231 cells in nude mice. RESULTS: The functional drug liposomes were able to induce cell cycle arrest at G2/M phase, induce apoptosis, inhibit adhesion, migration, and invasion of breast cancer cells in vitro, and prevent lung metastasis of breast cancer in nude mice. CONCLUSION: These findings indicate a potential clinical use of functional vincristine plus dasatinib liposomes for treating metastatic breast cancer.

Clinical drug interactions between linezolid and other antibiotics: For adverse drug event monitoring.

Detailed data on safety associated with drug-drug interactions (DDIs) between Linezolid (LZD) and other antibiotics are limited. The aim of this study was to investigate the safety signals related to these DDIs and to provide a reference for clinically related adverse drug event monitoring. Adverse event (AE) information from 1 January 2004 to 16 June 2022 of the target antibiotics including LZD using alone or in combination with LZD was extracted from the OpenVigil FDA data platform for safety signal analysis. The combined risk ratio model, reporting ratio method, Ω shrinkage measure model, and chi-square statistics model were used to analyze the safety signals related to DDIs. Meanwhile, we evaluated the correlation and the influence of sex and age between the drug(s) and the target AE detected. There were 18991 AEs related to LZD. There were 2293, 1726, 4449, 821, 2431, 1053, and 463 AE reports when LZD was combined with amikacin, voriconazole, meropenem, clarithromycin, levofloxacin, piperacillin-tazobactam, and azithromycin, respectively. Except for azithromycin, there were positive safety signals related to DDIs between LZD and these antibiotics. These DDIs might influence the incidence of 13, 16, 7, 7, 6, and 15 types of AEs, respectively, and is associated with higher reporting rates of AEs compared with use alone. Moreover, sex and age might influence the occurrence of AEs. We found that the combinations of LZD and other antibiotics are related to multiple AEs, such as hepatotoxicity, drug resistance and electrocardiogram QT prolonged, but further research is still required to investigate their underlying mechanisms. This study can provide a new reference for the safety monitoring of LZD combined with other antibiotics in clinical practice.

Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway.

ABSTRACT: Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts. In addition, AR silencing or treatment with the AR antagonist enzalutamide may increase the expression of circular RNA-deoxyhypusine synthase (circ-DHPS) in PCa cells, which can be transported to osteoblasts by exosomes. Circ-DHPS acts as a competitive endogenous RNA (ceRNA) against endogenous miR-214-3p to promote C-C chemokine ligand 5 (CCL5) levels in osteoblasts. Increasing the level of CCL5 in osteoblasts could recruit more PCa cells into the bone microenvironment. Thus, blocking the circ-DHPS/miR-214-3p/CCL5 signal may decrease exosome-mediated migration of prostate cancer cells to osteoblasts.

[Establishment of an animal model of prostate cancer metastasis to the lung traced by AsRed2].

OBJECTIVE: To establish an animal model of prostate cancer (PCa) metastasis to the lung using PCa PR7 (PCa PC-3 cells stably expressing red fluorescent protein AsRed2) cell lines that can be monitored by in vivo fluorescence imaging technology. METHODS: MTT and Transwell assay were used to compare the abilities of proliferation, migration and invasion of PC-3 and PR7 cells. Twenty BALB/c nude mice were equally randomized to 4 groups to receive tail vein injection of PR7 cell suspension at the concentration of 1 x 107/ml (group A), 2.5 x 107/ml (group B), 5 x 107/ml (group C) and 2.5 x 107/ml followed by the same dose 1 week later (group D). PCa metastasis to the lung was then monitored by in vivo fluorescence imaging technology at the end of 2, 4, 6 and 8 weeks. RESULTS: There were no statistically significant differences between PC-3 and PR7 cells in their abilities of proliferation, migration and invasion (P > 0.05). At the end of 4 weeks, lung metastasis was observed in 40% of the mice in group D, and at the end of 8 weeks, it was detected in 20% in group A, 60% in group B, 100% in group C, and 100% in group D, all confirmed by pathological examination. CONCLUSION: The animal model of PCa metastasis to the lung that can be monitored by in vivo fluorescence imaging technology was established successfully by tail vein injection of PR7 cells carrying red fluorescent protein.

Evaluation of nanoscaled dual targeting drug-loaded liposomes on inhibiting vasculogenic mimicry channels of brain glioma.

Brain glioma is the most common primary tumour of the central nervous system. Complete surgical removal of the brain glioma is virtually impossible. Chemotherapy is still an important treatment for brain glioma. However, blood-brain barrier (BBB) and vasculogenic mimicry (VM) channels remain two hindrances in regular treatments. Herein, we developed a novel nanoscaled dual targeting daunorubicin plus rofecoxib liposomes which could transport across the BBB, and eliminate brain glioma cells along with the VM channels. The liposomes were modified with two functional materials, and showed round in shape with a diameter about 120 nm. Evaluations were performed on human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. The dual targeting liposomes demonstrated a long circulatory effect in the blood system, were able to transport across the BBB, and were accumulated into the brain. The results indicated that the dual targeting daunorubicin plus rofecoxib liposomes could inhibit the brain glioma VM channels and exhibited a significant efficacy in the treatment of intracranial glioma-bearing nude mice. The mechanisms are related to down regulations MMP-2, MMP-9, FAK and HIF-α. Hence, the established dual targeting liposomes could be a potential formulation to treat the brain glioma along with eliminating VM channels.

Annexin A2 promotion of hepatocellular carcinoma tumorigenesis via the immune microenvironment.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a dismal prognosis, especially when diagnosed at advanced stages. Annexin A2 (ANXA2), is found to promote cancer progression and therapeutic resistance. However, the underlining mechanisms of ANXA2 in immune escape of HCC remain poorly understood up to now. Herein, we summarized the molecular function of ANXA2 in HCC and its relationship with prognosis. Furthermore, we tentatively elucidated the underlying mechanism of ANXA2 immune escape of HCC by upregulating the proportion of regulatory T cells and the expression of several inhibitory molecules, and by downregulating the proportion of natural killer cells and dendritic cells and the expression of several inhibitory molecules or effector molecules. We expect a lot of in-depth studies to further reveal the underlying mechanism of ANXA2 in immune escape of HCC in the future.

Inhibiting tumour metastasis by DQA modified paclitaxel plus ligustrazine micelles in treatment of non-small-cell lung cancer.

Lung cancer is a kind of malignant tumour characterized as uncontrolled cell growth in lung. These malignant cell growth can spread beyond the lung by process of metastasis into other tissues or parts of the body. In this study, we developed dequalinium (DQA) modified paclitaxel plus ligustrazine micelles to destroy vasculogenic mimicry (VM) channels and inhibit tumour metastasis. In vitro assays showed that the targeting micelles with centralized particle size distribution showed not only vigoroso cytotoxicity on A549 cells but also strong inhibition on VM channels and tumour metastasis. Mechanism studies indicated that the DQA modified paclitaxel plus ligustrazine micelles could down-regulate the expressions of VEGF, MMP2, TGF-ß1 and E-cadherin in A549 cells. In vivo assays indicated that the targeting drug-loaded micelles could enhance the accumulation of chemotherapeutic drugs at tumour sites and exhibit strong tumour inhibitory activity with negligible toxicity. Hence, the DQA modified paclitaxel plus ligustrazine micelles developed in this study may provide a potential strategy for treatment of NSCLC.

[Effects of trimetazidine on myocardial metabolism evaluated by PET-CT in patients with ischemic cardiomyopathy].

OBJECTIVE: Trimetazidine (TZM) has been shown to have anti-ischemia properties by optimizing ischemic myocardium metabolism. We evaluated the effect of TZM on myocardial metabolism with Positron Emission Computed Tomography (PET-CT) in patients with ischemic cardiomyopathy. METHODS: TZM (60 mg/d, n = 15) or placebo (n = 15) was randomly applied to ischemic cardiomyopathy patients on top of conventional therapy for 12 months. Color Doppler Flow Imaging (CDFI), (18)F-FDP PET-CT imaging and (99m)Tc-MIBI gated single photon emission computerized tomography (SPECT) imaging were performed at study begin and after 12 months. LVEF with CDFI, summed rest scores (SRS) with SPECT and standard uptake value (SUV) with PET-CT of the segments which were perfusion-metabolism matched and decreased were determined respectively. RESULTS: After 12 months, LVEF of the therapy group was increased from (37.9 +/- 5.0)% to (42.3 +/- 10.4)% (P < 0.05), while the control group increased from (37.9 +/- 4.6)% to (40.1 +/- 5.5)% (P > 0.05); SRSs of the matched segments of the therapy and the control were reduced from 3.9 +/- 1.0 to 2.4 +/- 2.3 (P < 0.01) and 4.0 +/- 0.7 to 2.8 +/- 1.8 (P < 0.05) respectively, while LVEF and SRSs were similar at study begin and after 12 months between these two groups. SUV of myocardial segments classified as myocardial perfusion-metabolism matched was increased from 5.3 +/- 1.5 to 9.8 +/- 4.7 in the therapy group (P < 0.05) and from 5.4 +/- 1.2 to 6.0 +/- 2.3 (P > 0.05) in the placebo group, SUV was significantly higher in the therapy group than that in placebo group after 12 months (P < 0.05). CONCLUSION: SPECT and (18)F-FDG imaging combination could be used to detect the surviving myocardium and chronic trimetazidine treatment could increase the glucose metabolism of ischemic cardiomyocytes in patients with ischemic cardiomyopathy.

Functional paclitaxel plus honokiol micelles destroying tumour metastasis in treatment of non-small-cell lung cancer.

Treatment effect of chemotherapy for aggressive non-small-cell lung cancer (NSCLC) is usually unsatisfactory for non-selective distributions of anticancer drugs, generation of vasculogenic mimicry (VM) channels, high metastasis and recurrence rate. Therefore, we developed a kind of dequalinium (DQA) modified paclitaxel plus honokiol micelles in this study to destroy VM channels and inhibit tumour metastasis. In vitro assays indicated that the targeting paclitaxel micelles with ideal physicochemical characteristics could exhibit not only the powerful cytotoxicity on Lewis lung tumour (LLT) cells but also the effective suppression on VM channels and tumour metastasis. Action mechanism studies manifested that DQA modified paclitaxel plus honokiol micelles could activate apoptotic enzymes caspase-3 and caspase-9 as well as down-regulate FAK, PI3K, MMP-2 and MMP-9. In vivo assays indicated that polymeric micelles could increase selective accumulation of chemotherapeutic drugs at tumour sites and showed a conspicuous antitumour efficacy. Hence, the DQA modified paclitaxel plus honokiol micelles prepared in this study provided a potential treatment strategy for NSCLC.

Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy.

BACKGROUND: The existing chemo/radiotherapy fail to eliminate cancer cells due to the restriction of either drug resistance or radio tolerance. The predicament urges researchers to continuously explore alternative strategy for achieving a potent curative effect. METHODS: Functional chlorin gold nanorods (Ce6-AuNR@SiO2-d-CPP) were fabricated aiming at treating breast cancer by photothermal/photodynamic therapy (PTT/PDT). The nanostructure was developed by synthesizing Au nanorods as the photothermal conversion material, and by coating the pegylated mesoporous SiO2 as the shell for entrapping photosensitizer Ce6 and for linking the D-type cell penetrating peptide (d-CPP). The function of Ce6-AuNR@SiO2-d-CPP was verified on human breast cancer MCF-7 cells and MCF-7 cells xenografts in nude mice. RESULTS: Under combinational treatment of PTT and PDT, Ce6-AuNR@SiO2-d-CPP demonstrated a strong cytotoxicity and apoptosis inducing effects in breast cancer cells in vitro, and a robust treatment efficacy in breast cancer-bearing nude mice. The uptake mechanism involved the energy-consuming caveolin-mediated endocytosis, and Ce6-AuNR@SiO2-d-CPP in PTT/PDT mode could induce apoptosis by multiple pathways in breast cancer cells. CONCLUSION: Ce6-AuNR@SiO2-d-CPP demonstrated a robust efficacy in the treatment of breast cancer by photothermal/photodynamic therapy. Therefore, the present study could offer a new promising strategy to treat the refractory breast cancer.

Vinorelbine cationic liposomes modified with wheat germ agglutinin for inhibiting tumor metastasis in treatment of brain glioma.

Glioma is the most common primary malignant brain tumor with a poor prognosis. The application of chemotherapeutic drugs is limited due to the existence of blood-brain barrier and serious side effects. Liposomes have been proven to be a stable and useful drug delivery system for tumors. In this paper, WGA (wheat germ agglutinin) modified vinorelbine cationic liposomes had been successfully constructed for treating glioma. In the liposomes, WGA was modified on the liposomal surface for crossing the blood-brain barrier and increasing the targeting effects, 3-(N-(N', N'-dimethylaminoethane) carbamoyl) cholesterol (DC-Chol) was used as cationic material and vinorelbine was encapsulated in the aqueous core of liposomes to inhibit tumor metastasis and kill tumor cells. Studies were performed on C6 cells in vitro and were verified in brain glioma-bearing mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce C6 cells apoptosis, promote drugs across the blood-brain barrier, inhibit the metastasis of tumor cells and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate PI3K, MMP-2, MMP-9 and FAK to inhibit tumor metastasis. Results in vivo exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and exhibited low toxicity to blood system and major organs. Hence, WGA modified vinorelbine cationic liposomes might provide a safe and efficient therapy strategy for glioma.

Lipid vesicles containing transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8 efficiently treat brain glioma along with glioma stem cells.

Surgery and radiotherapy cannot fully remove brain glioma; thus, chemotherapy continues to play an important role in treatment of this illness. However, because of the restriction of the blood-brain barrier (BBB) and the regeneration of glioma stem cells, post-chemotherapy relapse usually occurs. Here, we report a potential solution to these issues that involves a type of novel multifunctional vinblastine liposomes equipped with transferrin receptor binding peptide TfR-T12 and octa-arginine conjugate stearyl-R8. Studies were performed on brain glioma and glioma stem cells in vitro and were verified in brain glioma-bearing mice. The liposomes were transported across the BBB, killing brain glioma and glioma stem cells via the induction of necrosis, apoptosis and autophagy. Furthermore, we reveal the molecular mechanisms for treating brain glioma and glioma stem cells via functionalized drug lipid vesicles.

Destruction of vasculogenic mimicry channels by targeting epirubicin plus celecoxib liposomes in treatment of brain glioma.

The efficacy of chemotherapy for brain glioma is restricted by the blood-brain barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the treatment of intracranial glioma-bearing nude mice. Therefore, targeting epirubicin plus celecoxib liposomes could be a potential nanostructured formulation to treat gliomas and destroy their VM channels.

Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating Brain Glioma and Glioma Stem Cells.

The highly infiltrative nature of brain glioma makes total surgical removal of cancerous cells virtually impossible. Regular chemotherapy plays an important role in eradicating the residual cancer cells but is ineffective in treating brain glioma due to the hindrance of drug penetration into the tumor site by the blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem cells (GSCs). In this study, functional targeting daunorubicin liposomes were developed by modifying the liposomes with distearoylphosphatidylethanolamine polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the glioma stem cells. The results showed that the functional targeting daunorubicin liposomes were able to significantly transfer across the BBB and exhibited an obvious efficacy in killing glioma and glioma stem cells in mice. The action mechanisms of the functional targeting daunorubicin liposomes were related to their properties: long-duration circulation in the blood system, transport capability across the BBB, concentrated accumulation in the brain glioma site, and increased internalization by malignant cells and their mitochondria. This functional drug formulation showed anticancer efficacy through a direct cytotoxic effect and an apoptosis-inducing effect through the apoptotic signaling pathways in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for treating brain glioma, functional targeting daunorubicin liposomes have the potential to eliminate brain glioma along with glioma stem cells.

A nanostructure of functional targeting epirubicin liposomes dually modified with aminophenyl glucose and cyclic pentapeptide used for brain glioblastoma treatment.

The objectives of the present study were to develop functional targeting epirubicin liposomes for transferring drugs across the blood-brain barrier (BBB), treating glioblastoma, and disabling neovascularization. The studies were performed on glioblastoma cells in vitro and on glioblastoma-bearing mice. The results showed that the constructed liposomes had a high encapsulation efficiency for drugs (>95%), suitable particle size (109 nm), and less leakage in the blood component-containing system; were significantly able to be transported across the BBB; and exhibited efficacies in killing glioblastoma cells and in destroying glioblastoma neovasculature in vitro and in glioblastoma-bearing mice. The action mechanisms of functional targeting epirubicin liposomes correlated with the following features: the long circulation in the blood system, the ability to be transported across the BBB via glucose transporter-1, and the targeting effects on glioblastoma cells and on the endothelial cells of the glioblastoma neovasculature via the integrin ß3 receptor. In conclusion, functional targeting epirubicin liposomes could be used as a potential therapy for treating brain glioblastoma and disabling neovascularization in brain glioblastomas.

Application of functional vincristine plus dasatinib liposomes to deletion of vasculogenic mimicry channels in triple-negative breast cancer.

Standard chemotherapy cannot eradicate triple-negative breast cancer (TNBC) while the residual cancer cells readily form the vasculogenic mimicry (VM) channels, which lead to the relapse of cancer after treatment. In this study, the functional vincristine plus dasatinib liposomes, modified by a targeting molecule DSPE-PEG2000-c(RGDyK), were fabricated to address this issue. The investigations were performed on TNBC MDA-MB-231 cells and MDA-MB-231 xenografts in nude mice. The liposomes exhibited the superior performances in the following aspects: the enhancement of cellular uptake via targeted action; the induction of apoptosis via activation of caspase 8, 9, and 3, increased expression of Bax, decreased expression of Mcl-1, and generation of reactive oxygen species (ROS); and the deletion of VM channels via inhibitions on the VM channel indicators, which consisted of vascular endothelial-cadherin (VE-Cad), focal adhesion kinase (FAK), phosphatidylinositide 3-kinase (PI3K), and matrix metallopeptidases (MMP-2, and MMP-9). Furthermore, the liposomes displayed the prolonged circulation time in the blood, the increased accumulation in tumor tissue, and the improved therapeutic efficacy along with deletion of VM channels in the TNBC-bearing mice. In conclusion, the nanostructured functional drug-loaded liposomes may provide a promising strategy for the treatment of invasive TNBC along with deletion of VM channels.

Relationships among androgen receptor CAG repeat polymorphism, sex hormones and penile length in Han adult men from China: a cross-sectional study.

This study aimed to investigate the correlations among androgen receptor (AR) CAG repeat polymorphism, sex hormones and penile length in healthy Chinese young adult men. Two hundred and fifty-three healthy men (aged 22.8 ± 3.1 years) were enrolled. The individuals were grouped as CAG short (CAG S ) if they harbored repeat length of ≤ 20 or as CAG long (CAG L ) if their CAG repeat length was >20. Body height/weight, penile length and other parameters were examined and recorded by the specified physicians; CAG repeat polymorphism was determined by the polymerase chain reaction (PCR) method; and the serum levels of the sex hormones were detected by radioimmunoassay. Student's t-test or linear regression analysis was used to assess the associations among AR CAG repeat polymorphism, sex hormones and penile length. This investigation showed that the serum total testosterone (T) level was positively associated with the AR CAG repeat length (P = 0.01); whereas, no significant correlation of T or AR CAG repeat polymorphism with the penile length was found (P = 0.593). Interestingly, an inverse association was observed between serum prolactin (PRL) levels and penile length by linear regression analyses (ß= -0.024, P = 0.039, 95% confidence interval (CI): -0.047, 0). Collectively, this study provides the first evidence that serum PRL, but not T or AR CAG repeat polymorphism, is correlated with penile length in the Han adult population from northwestern China.

Brain areas involved in acupuncture treatment on functional dyspepsia patients: a PET-CT study.

Neuroimaging studies on brain responses to acupuncture stimulations have received considerable attention recently. The majority of these studies are centered on healthy controls (HC) and neuropathy, while little work has addressed other disorders. This study aimed to investigate the influence of acupuncture stimulations on brain activities in functional dyspepsia (FD) patients. Eight FD patients and eight healthy controls (HC) were involved in this study. Each HC received an 18F-FDG PET-CT scan at baseline, while each patient received scans at baseline and after acupuncture stimulations. Manual acupuncture stimulations were performed at ST34 (Liangqiu), ST36 (Zusanli), ST40 (Fenglong) and ST42 (Chongyang) in FD patients. The images were analyzed with the Statistical Parametric Mapping software 2.0. Compared to HC, the FD patients showed a lower glycometabolism in the right orbital gyrus, the left caudate tail and the cingulate gyrus, and a higher glycometabolism in the left inferior temporal gyrus (p<0.005). After acupuncture stimulations, the FD patients showed a glycometabolism decrease in the postcentral gyrus and the cerebella, and an increase in the visual-related cortices(p<0.005). The results suggest that the anterior cingulate cortex, the prefrontal cortices and the caudate tail involve in processing gastric perceptions in FD patients and that the deactivation of the primary somatosensory area and the cerebella is contributable to acupuncture stimulation, while activation of the visual-related cortex is a response to pain or acupoint actions.