The Influence of Preoperative Waiting Time on Anxiety and Pain Levels in Outpatient Surgery for Breast Diseases.

OBJECTIVE: This study aims to examine the effects of different preoperative waiting times on anxiety and pain levels in patients undergoing outpatient surgery for breast diseases, providing insights for clinical interventions during the perioperative phase. METHODS: Patients who underwent outpatient surgery at a hospital breast center in Ningbo between January 2021 and December 2021 were selected. Their anxiety levels at the time when they entered the preoperative preparation room and when they ended the postoperative waiting period for the rapid frozen section procedure were assessed using the State Anxiety Inventory (S-AI) questionnaire, and their pain levels at the end of the postoperative waiting period were assessed using the short-form McGill Pain Questionnaire. The patients enrolled were divided into 3 groups according to the preoperative waiting time: <2 hours (T1 group), 2 to 4 hours (T2 group), and >4 hours (T3 group); there were 150 patients in each group, and the anxiety and pain levels were compared between the groups. RESULTS: At the time of entering the preoperative preparation room, patients' S-AI score T1 = T2 ( P > 0.05), both T1 and T2 < T3 ( P < 0.05); however, at the time of the postoperative waiting period, patients' S-AI score was T1 < T2 < T3 ( P < 0.05), and the postoperative waiting period patients' short-form McGill Pain Questionnaire scores were T1 = T2 < T3 ( P < 0.05). CONCLUSIONS: The perioperative anxiety and pain levels of patients undergoing outpatient breast surgery increased with the prolongation of preoperative waiting time; 4 hours was the critical time point for change, after which the anxiety and pain levels of patients increased significantly.

The value of inflammatory biomarkers in the occurrence and prognosis of sudden sensorineural hearing loss: a meta-analysis.

OBJECTIVES: Sudden sensorineural hearing loss (SSNHL) is one of the common emergencies in otorhinolaryngology. Several studies have shown that chronic inflammation is associated with its onset and prognosis. However, the association between some inflammatory biomarkers and SSNHL is still unclear. Therefore, we conducted this meta-analysis to explore the value of inflammatory biomarkers in the occurrence and prognosis of SSNHL. METHODS: Pubmed, Embase, Cochrane and Web of Science databases were searched comprehensively, the eligible literatures were screened out by formulating the inclusion criteria and exclusion criteria. After extracting sample size, mean and standard deviation, we performed meta-analysis with standardized mean deviation (SMD) and 95% confidence interval (CI) as effect sizes. RESULTS: A total of 17 articles were included in this meta-analysis, including 2852 subjects, 1423 patients and 1429 healthy controls. The results of meta-analysis showed that the neutrophil-to-lymphocyte ratio (NLR) of the experimental group was significantly higher than the control group (SMD = 1.05, 95% CI 0.87-1.24, P < 0.001), the NLR of the recovery group was significantly lower than the unrecovered group (SMD = 0.68, 95% CI 0.27-1.08, P < 0.05); The platelet-to-lymphocyte ratio (PLR) of the experimental group was significantly higher than the control group (SMD = 0.55, 95% CI 0.34-0.76, P < 0.05), the PLR of the recovery group was significantly lower than the unrecovered group (SMD = 0.44, 95% CI 0.05-0.82, P < 0.05); The C-reactive protein-to-serum albumin ratio (CRP/Alb) of the experimental group was significantly higher than the control group (SMD = 0.39, 95% CI 0.04-0.74, P < 0.05). CONCLUSIONS: The results showed that high NLR, PLR, and CRP/Alb indicated the occurrence of SSNHL, NLR and PLR could predict prognosis of SSNHL.

Role of Exosomes in Pharyngucutaneous Fistula After Total Laryngectomy.

Pharyngocutaneous fistula is the most common complication after total laryngectomy and is difficult to heal. Although conservative treatment and surgical repair are effective, they often take longer and additional trips to the operating room, which undoubtedly increases the financial burden on patients. Especially in combination with diseases such as diabetes and hypertension, which affect the efficacy of surgery. Adding growth factors into the repair material can promote fibroblast proliferation, angiogenesis, and accelerate wound healing. A substantial number of studies have shown that a type of nanoscale extracellular vesicle, called exosomes, facilitates organization repair by promoting blood vessel production, protein polysaccharides, and collagen deposition, thereby representing a new type of cellular therapy. At present, there is little research on the application of exosomes in pharyngocutaneous fistula regeneration after total laryngectomy. In this review, we summarize the biological characteristics of exosomes and their application in biomedical science, and highlight their application prospects in pharyngocutaneous fistula regeneration after total laryngectomy.

Identification and validation of a novel 16-gene prognostic signature for patients with breast cancer.

Despite increased early diagnosis and improved treatment in breast cancer (BRCA) patients, prognosis prediction is still a challenging task due to the disease heterogeneity. This study was to identify a novel gene signature that can accurately evaluate BRCA patient survival. The gene expression and clinical data of BRCA patients were collected from The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of BRCA International Consortium (METABRIC) databases. Genes associated with prognosis were determined by Kaplan-Meier survival analysis and multivariate Cox regression analysis. A prognostic 16-gene score was established with linear combination of 16 genes. The prognostic value of the signature was validated in the METABRIC and GSE202203 datasets. Gene expression analysis was performed to investigate the diagnostic values of 16 genes. The 16-gene score was associated with shortened overall survival in BRCA patients independently of clinicopathological characteristics. The signalling pathways of cell cycle, oocyte meiosis, RNA degradation, progesterone mediated oocyte maturation and DNA replication were the top five most enriched pathways in the high 16-gene score group. The 16-gene nomogram incorporating the survival-related clinical factors showed improved prediction accuracies for 1-year, 3-year and 5-year survival (area under curve [AUC] = 0.91, 0.79 and 0.77 respectively). MORN3, IGJ, DERL1 exhibited high accuracy in differentiating BRCA tissues from normal breast tissues (AUC > 0.80 for all cases). The 16-gene profile provides novel insights into the identification of BRCA with a high risk of death, which eventually guides treatment decision making.

Hippo/YAP signaling pathway protects against neomycin-induced hair cell damage in the mouse cochlea.

The Hippo/Yes-associated protein (YAP) signaling pathway has been shown to be able to maintain organ size and homeostasis by regulating cell proliferation, differentiation, and apoptosis. The abuse of aminoglycosides is one of the main causes of sensorineural hearing loss (SSNHL). However, the role of the Hippo/YAP signaling pathway in cochlear hair cell (HC) damage protection in the auditory field is still unclear. In this study, we used the YAP agonist XMU-MP-1 (XMU) and the inhibitor Verteporfin (VP) to regulate the Hippo/YAP signaling pathway in vitro. We showed that YAP overexpression reduced neomycin-induced HC loss, while downregulated YAP expression increased HC vulnerability after neomycin exposure in vitro. We next found that activation of YAP expression inhibited C-Abl-mediated cell apoptosis, which led to reduced HC loss. Many previous studies have reported that the level of reactive oxygen species (ROS) is significantly increased in cochlear HCs after neomycin exposure. In our study, we also found that YAP overexpression significantly decreased ROS accumulation, while downregulation of YAP expression increased ROS accumulation. In summary, our results demonstrate that the Hippo/YAP signaling pathway plays an important role in reducing HC injury and maintaining auditory function after aminoglycoside exposure. YAP overexpression could protect against neomycin-induced HC loss by inhibiting C-Abl-mediated cell apoptosis and decreasing ROS accumulation, suggesting that YAP could be a novel therapeutic target for aminoglycosides-induced sensorineural hearing loss in the clinic.

Determination, Isolation, and Identification of Related Impurities in Erdosteine Bulk Drug.

BACKGROUND: Erdosteine is a mucolytic drug and has antioxidant activity. OBJECTIVE: The study aimed to develop an HPLC method for determination of erdosteine and its impurities in erdosteine bulk drug and to identify the main impurities to help improve the quality of erdosteine bulk drug. METHOD: The chromatographic separations were performed on a CAPCELL PAK C18 column (250 mm × 4.6 mm id, 5 µm). Acetonitrile-0.01 mol/L citric acid solution (13 + 87, by volume) pumped at a flow rate of 1.0 mL/min was used as the mobile phase. The detection wavelength was 254 nm. Two main impurities in erdosteine bulk drug were enriched by an ODS column chromatography and oxidative degradation, respectively, and then both were purified by semipreparative HPLC. Finally, their structures were identified by a variety of spectral data (MS, 1H NMR and 13C NMR). RESULTS: Good separations of erdosteine and its related impurities were observed. A new impurity was confirmed as ethyl ({2-oxo-2-[(2-oxotetrahydro-3-thiophenyl) amino] ethyl} sulfanyl)acetate, which was erdosteine ethyl ester, and was produced in the refining process of erdosteine bulk drug when using ethanol as a refining solvent. Another impurity was confirmed as ({2-oxo-2-[(2-oxotetrahydro-3-thiophenyl)amino]ethyl}sulfinyl) acetic acid, which was an erdosteine oxide. CONCLUSIONS: An HPLC method for determination of erdosteine and its related impurities was developed and validated. Two main impurities in erdosteine bulk drug were isolated and identified. Avoiding ethanol as the refining solvent can improve the purity of erdosteine bulk drug. HIGHLIGHTS: A new process-related impurity and an oxidative degradation impurity in erdosteine bulk drug were isolated and identified.

Clinical efficacy and safety of MP-AzeFlu for the treatment of allergic rhinitis: a meta-analysis.

OBJECTIVE: MP-AzeFlu is a novel option for therapy of allergic rhinitis (AR). The purpose of our study was to assess the safety and efficacy of MP-AzeFlu for the treatment of allergic rhinitis, compared to placebo and azelastine monotherapy. METHODS: The PubMed, MEDLINE, EMBASE and Cochrane databases were comprehensively searched for all published randomized controlled trials (RCTs) of using MP-AzeFlu nasal spray on July 26, 2019. In these studies, we selected patients with clinical symptom scores. The heterogeneity of the included studies was assessed by I2. RESULTS: Among the 336 citations retrieved, 6 articles with over 6000 patients were finally included in the meta-analysis. The results of meta-analysis revealed that MP-AzeFlu was superior to placebo ( - 2.43 [95%CI,  - 2.73 to  - 2.14], P < 0.00001) and azelastine ( - 1.27 [95% CI,  - 1.57 to  - 0.97], P < 0.00001) in reflective total nasal symptom score. In the MP-AzeFlu group, the instantaneous total nasal symptom score ( - 2.56 [95% CI,  - 3.02 to  - 2.10], P < 0.00001) and the reflective total ocular symptom score ( - 1.22 [95% CI,  - 1.57 to  - 0.87], P < 0.00001) were significantly reduced compared to the placebo group. CONCLUSION: MP-AzeFlu is as safe and mild as placebo and azelastine, which also is associated with symptom relief and the improvement of quality of life in AR patients. MP-AzeFlu can provide better clinical benefits than two currently available first-line intranasal therapies. It is an ideal therapy for AR patients.

Development and Validation of a Sensitive GC-MS/MS Method for the Determination of Five Potential Genotoxic Impurities in Abiraterone Acetate.

A sensitive and selective gas chromatography-tandem mass spectrometry method was developed for the identification and quantification of five potential genotoxic impurities (PGIs), i.e., chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate, in abiraterone acetate. The method was validated according to the International Council for Harmonisation (ICH) guidelines. The linearity was established for the concentration range of 30-480 ng/mL (2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate) and 90-1440 ng/mL (chloromethane). The correlation coefficient of each PGIs was >0.995. The extraction recoveries ranged from 90.49 to 106.79% for the five PGIs. The quantitation limit, detection limit, accuracy, precision, repeatability and stability of the method demonstrated that the method was an adequate quality control tool for quantitation and identification of chloromethane, 2-chloropropane, 2-bromopropane, 4-chloro-1-butanol and diethyl sulfate at trace levels in drug substances and drug products.

Identification and quantification of five impurities in cloperastine hydrochloride.

Cloperastine hydrochloride, a piperidine derivative, is a drug substance with a central antitussive effect and widely used in cough treatment; and its impurities have not been reported. Herein we isolated and identified five impurities (named as impurity A, B, C, D and E) in cloperastine hydrochloride bulk drug and developed a quantitative HPLC method. First, impurity A, B, C were enriched by ODS column chromatography and isolated by semi-preparative HPLC, at the same time, impurity D was purified by ODS column chromatography. Then, impurity E was enriched by strong acid degradation and purified by semi-preparative HPLC. At last, their structures were characterized by a variety of spectral data (MS, 1H NMR, 13C NMR, HSQC, HMBC and 1H-1H COSY). Impurity A was confirmed as 1-[2-(diphenylmethoxy)ethyl]piperidine, which having one less chloro-substituent compared with cloperastine. Impurity B was confirmed as 1-[2-[(2-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 2-chloro-substituent. Impurity C was confirmed as 1-[2-[(3-chlorophenyl)(phenyl)methoxy]ethyl]piperidine, which was the isomer of cloperastine with 3-chloro-substituent. Impurity D was confirmed as (4-chlorophenyl)(phenyl)methanone, which was the raw material for the synthesis of cloperastine. Impurity E was confirmed as (4-chlorophenyl)(phenyl)methanol, which was an intermediate in the synthesis of cloperastine, and it was also a hydrolysate of cloperastine. Finally, the developed method was validated in terms of specificity, linearity, sensitivity, precision and accuracy.

Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage.

Aminoglycoside-induced hair cell (HC) loss is one of the most important causes of hearing loss. After entering the inner ear, aminoglycosides induce the production of high levels of reactive oxygen species (ROS) that subsequently activate apoptosis in HCs. Citicoline, a nucleoside derivative, plays a therapeutic role in central nervous system injury and in neurodegenerative disease models, including addictive disorders, stroke, head trauma, and cognitive impairment in the elderly, and has been widely used in the clinic as an FDA approved drug. However, its effect on auditory HCs remains unknown. Here, we used HC-like HEI-OC-1 cells and whole organ explant cultured mouse cochleae to explore the effect of citicoline on aminoglycoside-induced HC damage. Consistent with previous reports, both ROS levels and apoptosis were significantly increased in neomycin-induced cochlear HCs and HEI-OC-1 cells compared to undamaged controls. Interestingly, we found that co-treatment with citicoline significantly protected against neomycin-induced HC loss in both HEI-OC-1 cells and whole organ explant cultured cochleae. Furthermore, we demonstrated that citicoline could significantly reduce neomycin-induced mitochondrial dysfunction and inhibit neomycin-induced ROS accumulation and subsequent apoptosis. Thus, we conclude that citicoline can protect against neomycin-induced HC loss by inhibiting ROS aggregation and thus preventing apoptosis in HCs, and this suggests that citicoline might serve as a potential therapeutic drug in the clinic to protect HCs.

Serum Human Epidermal Growth Factor 2 is a Novel Biomarker for Recurrence and Metastasis in Triple Negative Breast Cancer.

BACKGROUND: The aim of this study was to evaluate the predictive value of serum human epidermal growth factor 2 (HER2) for recurrence and metastasis in triple negative breast cancer (TNBC). METHODS: A total of 200 patients with benign breast tumors and 300 patients with breast cancer treated in the Department of Breast Surgery, Women and Children's Hospital of Ningbo City (China) between December 2006 and December 2013 were enrolled. Another 500 age- and gender-matched healthy individuals served as controls. The serum level of HER2 was determined using suspension array technology. Patients with breast cancer were further divided into ER-/PR-/HER2- and ER-/PR-/HER2+ groups and followed up for 5 years to analyze the serum concentration of HER2. RESULTS: The serum HER2 concentration was significantly higher in patients with breast cancer than in healthy controls or patients with benign tumors (both p < 0.01). The serum HER2 concentration also was significantly higher in patients with TNBC than in healthy controls (p < 0.01). The serum concentration of HER2 was significantly higher in TNBC patients who experienced recurrence and metastasis than in TNBC patients who did not experience recurrence and metastasis (both p < 0.01). Notably, the serum HER2 concentration in TNBC patients who experienced recurrence and metastasis was increased to a level statistically similar to that in patients with HER2+ breast cancer (p > 0.05). CONCLUSIONS: Patients with TNBC still have an increased serum HER2 concentration, and serum HER2 may be a valuable, novel biomarker for recurrence and metastasis in TNBC.

[Clinal analysis of 202 nasal bone fractures cases].

OBJECTIVE: To evaluate the age, sex, etiology, diagnosis and treatment time of nasal bone fractures. METHOD: Clinical data of 202 cases with nasal bone fractures treated in the hospital were retrospectively analysed. RESULT: A total of 202 cases,163 men (80. 7%) and 39 women (19. 3%). Fifty-two patients had a relationship with alcohol consumption, and all of them were males. The most frequent reasons of the injury were fight 46. 5% (94 cases) followed by falling-down 21. 3% (43 cases), traffic accidents 19. 3% (39 cases), works related 6. 5% (13 cases), sport injuries 5. 9% (12 cases) and others 0. 5% (1 cases). Patients distribution in seasons were: spring 54 cases (26.7%), summer 42 cases (20.8%), autumn 58 cases (28.7%), winter 48 cases (23. 8%). Diagnosis of nasal bone fractures were made positively by x-ray films in 79. 7% of cases, but 100% by CT. Positive predictive value of CT was superior to that of X-ray films in the diagnosis of nasal bone fracture. CONCLUSION: High morbidity of nasal bone fracture was seen in the age group of 20-29 years, and predominantly in male. Fight was found to be the main etiologic factor. We think that CT is necessary for diagnosing nasal bone fracture.

[The study on the relationship between human papillomavirus infection and pathogenesis of nasal inverted papilloma and its malignant transformation].

OBJECTIVE: To investigate the relationship between human papillomavirus (HPV) infection and pathogenesis of nasal inverted papilloma (NIP) and its malignant transformation. METHOD: Fifty-seven cases of NIP were divided into 2 groups: benign group, squamous cell carcinoma (SCC) arising in NIP group (malignancy group). HPV-DNA types of 6, 11, 16, 18 were detected by polymerase chain reaction (PCR) in 57 cases of NIP. Thirty cases of nasal polyps were control. RESULT: Total positive rate of HPV in NIP was 64.9% (37/57). The positive rate of benign group was 60% (27/45), all with single and low risk HPV11 type infection. The positive rate of malignancy group were was 83.3% (10/12), and the majority were HPV16 and HPV18. Five cases had double infection (4 with HPV16 and HPV 18, 1 with HPV11 and HPV18), four had single HPV16 infection, another one had single HPV11 infection. However, HPV-DNA was not detected in any cases of nasal polyps. CONCLUSION: Infection of HPV-DNA has an important effect in pathogenesis of NIP. Meanwhile, there maybe a close relationship between high risk HPV16 type and HPV18 type and malignant transformation of NIP.

Keratin 17 identified by proteomic analysis may be involved in tumor angiogenesis.

Angiogenesis is crucial for solid tumor growth. By secreting angiogenic factors, tumor cells induce angiogenesis. However, targeting these angiogenic factors for cancer therapy is not always successful, suggesting that other factors may be involved in tumor angiogenesis. This work shows that 25 protein spots were differentially expressed by two-dimensional gel electrophoretic analysis when HepG2 cells induced endothelial cell differentiation to tube in vitro, and most of them were upregulated. Twenty-one proteins were identified with MALDI-TOF-MS, and the other four were identified by LTQ-MS/MS. Keratins were identified as one class of these upregulated proteins. Further study indicated that the expression of keratin 17 in cultured endothelial cells is likely microenvironment regulated, because its expression can be induced by HepG2 cells and bFGF as well as serum in culture media. Increased expression of keratins in endothelial cells, such as keratin 17, may contribute to the angiogenesis induced by HepG2 cells.

[BFGF entraped in cationic liposomes as adjuvant: optimization of technical parameters].

OBJECTIVE: To test the immune efficiency of bFGF entraped in cationic liposomes as adjuvant in vivo. METHODS: The technical parameters on encapsulation were tested in each step to gain high encapsulation efficiencies, which included lipid composition, weight ratio of protein and lipids, liposome extrusion, and different conditions of freeze-thawing. The bFGF in cationic liposome, Freund's adjuvant, or PBS were injected (four times) to the four-week old Balb/c mice to test the immune responses. The serum antibody was measured by ELISA 13 days after each injection. RESULTS: Maximal encapsulation efficiency (about 50%) was achieved through optimized technical parameters. Cationic liposome demonstrated satisfied immune efficiency as adjuvant. CONCLUSION: Cationic liposome is a safe and effective immunological adjuvant.

[An experimental study on the role of keratin in angiogenesis in vitro].

OBJECTIVE: To investigate the effect of keratin 17 (K-17) on the migration, proliferation and tube formation of human umbilical vein endothelial cell (HUVEC), and to realize the role of K-17 in angiogenesis. METHODS: After HUVEC were cultured in DMEM medium supplemented with 10%FBS overnight, K-17-siRNA-mixture (experimental group) and control-siRNA-mixture (negative control group) were added into HUVEC, respectively, by Lipofectamine 2000 transfection assay, and the final concentration of the siRNA was 50 nmol/L. Lipofectamine 2000 alone was used as the control. After the cells were cultured for 36 hours, the cell proliferation ability was detected by cell counting. After 30-hour culture, the cell's abilities of migration and differentiation to tube were detected by 24-well Millicell units and the collagen gel assay, respectively. In addition, non-siRNA-treated HUVEC were cultured for 24 hours in DMEM medium supplemented with 10%FBS (group A), 2%FBS (group B) and 2%FBS+10 ng/mL bFGF (group C), respectively, and then the expression of K-17 in HUVEC was detected by RT-PCR and Western blot. RESULTS: After the treatment with K-17-siRNA for 36 hours, HUVEC exhibited no significant difference in the proliferation, compared with both control and negative control groups (P > 0.05). After transfected with K-17-siRNA for 30 hours, the number of HUVEC in the experimental group which migrated from the upper chamber to the lower chamber of Millicell wells within 24 hours (3719.0 +/- 319.0) was smaller than both control (7 437.5 +/- 212.0) and negative control (7 356.3 +/- 795.7) groups, with significant difference (P < 0.01). However, there was no significant difference between the control group and the negative control group (P > 0.05). After HUVEC were transfected with K-17-siRNA for 30 hours, the number of tubes in the experimental group, the negative control group and the control group in 24 hours was (1.1 +/- 0.5), (3.6 +/- 0.5) and (3.2 +/- 0.6) per field, respectively. The experimental group was significantly different from both control and negative control groups (P < 0.01), and there was no significant difference between the negative control group and the control group (P > 0.05). The expression of K-17 protein in HUVEC in groups A, B and C was 0.25 +/- 0.02, 0.08 +/- 0.01 and 0.72 +/- 0.03, respectively. There was significant difference among these three groups (P < 0.01). CONCLUSION: K-17 has no impact on cell proliferation, but may augment endothelial cell migration, which may facilitate angiogenesis.

[Effects of honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro].

OBJECTIVE: To assess the effects of honokiol on proliferation and apoptosis of human cervical carcinoma cell line Hela in vitro. METHODS: Cultured HeLa cells were treated with different concentrations of honokiol for the varieties of period (24, 48, 72, 96 h). Cell proliferation was assessed by MTT colorimetric assay. Cell apoptosis was determined by flow cytometry (FCM), Hoechst 33258 fluorescent staining and DNA ladder respectively. RESULTS: MTT assay demonstrated that the proliferation of Hela cells were suppressed significantly by honokiol in dose-and time-dependent manner. FCM analysis showed that the apoptosis rates of Hela cells treated with 10 microg/mL and 20 microg/mL honokiol for 24 h were 22.5% and 62.2%, respectively, while that of the control group cells was 8.7%. After treatment with honokiol, typically morphologic changes of apoptosis were observed by Hoechst 33258 fluorescence staining; Genomic DNA from Hela cells treated with honokiol displayed a characteristic ladder pattern on agarose gel electrophoresis. CONCLUSION: honokiol can inhibit the proliferation and induce apoptosis of human cervical carcinoma cell line Hela.

Synergistic antitumor effects of liposomal honokiol combined with adriamycin in breast cancer models.

Honokiol, a novel antitumor agent, could induce apoptosis and inhibit the growth of vascular endothelium in several tumor cell lines and xenograft models. It has been suggested that the antitumor effect of chemotherapy could be increased by combining it with an antiangiogenesis agent in anticancer strategy. The present study explored the potential to increase the antitumor effect of adriamycin by combining it with honokiol in mouse 4T1 breast cancer models, and the underlining mechanism was investigated. Honokiol was encapsulated in liposomes to improve the water insolubility. In vitro, liposomal honokiol inhibited the proliferation of 4T1 cells via apoptosis and significantly enhanced the apoptosis of 4T1 cells induced by adriamycin. In vivo, the systemic administration of liposomal honokiol and adriamycin significantly decreased tumor growth through increased tumor cell apoptosis compared with either treatment alone. Collectively, these findings suggest that liposomal honokiol may augment the induction of apoptosis in 4T1 cells in vitro and in vivo, and this combined treatment has shown synergistic suppression in tumor progression according to the analysis of isobologram. The present study may be important in future exploration of the potential application of the combined approach in the treatment of breast cancer.

Isolation and purification of ginkgo flavonol glycosides from Ginkgo biloba leaves by high-speed counter-current chromatography.

A high-speed counter-current chromatography method was developed for the separation and purification of bioactive flavonol glycosides from a crude ethanol extract of Ginkgo biloba leaves. The separation was performed with a two-phase solvent system composed of n-hexane-butanol-ethyl acetate-methanol-0.5% acetic acid (1:0.5:3.5:1:4, v/v) and three pure compounds were eluted in high purities in a one-step separation. Their purities were determined by HPLC and identified by MS,(1)H-NMR, and(13)C-NMR.