A U-shaped association between serum betaine and incident risk of first ischemic stroke in hypertensive patients.

BACKGROUND & AIMS: Betaine (a micronutrient) has important biological functions (e.g., preventing premature apoptosis and serving as a methyl donor). We investigated the association between baseline serum betaine and the incident risk of first stroke in hypertensive patients. METHODS: We conducted a nested case-control study, including 622 patients with first stroke (including 502 ischemic stroke, 118 hemorrhagic stroke and 2 uncertain type of stroke) and 622 matched controls from the China Stroke Primary Prevention Trial (CSPPT). The study was conducted from May 2008 to August 2013. The study outcomes included first stroke and its subtypes: first ischemic and hemorrhagic stroke. RESULTS: There was a U-shaped association between baseline serum betaine and the risk of first ischemic stroke. The risk of first ischemic stroke decreased with the increment of betaine (per 10 µmol/L increase: OR, 0.87; 95%CI: 0.77-0.99) in patients with betaine <77.7 µmol/L, while the risk of first ischemic stroke increased with the betaine increment (OR, 1.17; 95%CI: 1.01-1.36) in patients with betaine ≥77.7 µmol/L. However, there was no significant association between serum betaine and risk of first hemorrhagic stroke (per 10 µmol/L increase: OR, 0.98; 95%CI: 0.82-1.17). CONCLUSIONS: There was a U-shaped association between baseline betaine levels and the risk of first ischemic stroke in hypertensive patients, with a turning point at about 77.7 µmol/L. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Down-regulated long non-coding RNA RNAZFHX4-AS1 suppresses invasion and migration of breast cancer cells via FAT4-dependent Hippo signaling pathway.

Breast cancer is ranked as the second leading cause of cancer-related deaths among women. Accumulating evidences have revealed that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis owing to the regulation of essential pathways for tumor initiation and progression. Herein, the current study aimed to explore the regulatory mechanism of lncRNA ZFHX4-AS1 in breast cancer in relation to the Hippo signaling pathway. Initially, microarray analysis was conducted to screen out differentially expressed lncRNAs related to breast cancer. Next, the functional role of lncRNA ZFHX4-AS1 in breast cancer was determined using ectopic expression, knockdown, and reporter assay experiments. Subsequently, lncRNA ZFHX4-AS1, TAF4, TAZ, and YAP expressions were determined, followed by verification of the targeting relationship between lncRNA ZFHX4-AS1 and TAF4. Then cell proliferation, invasion, migration, cell cycle, and apoptosis were measured. Lastly, tumor growth and metastasis were detected by tumor xenograft in nude mice. LncRNA ZFHX4-AS1 was found to be highly expressed while FAT4 was poorly expressed in breast cancer tissues. FAT4 was the target gene of lncRNA ZFHX4-AS1, and lncRNA ZFHX4-AS1 silencing increased FAT4 expressions, while decreased YAP and TAZ expressions. In addition, knockdown of lncRNA ZFHX4-AS1 suppressed breast cancer cell proliferation, migration, and invasion as well as tumor growth, blocked cell cycle entry, while promoted cell apoptosis by inhibiting the Hippo signaling pathway. In conclusion, our findings reveal that lncRNA ZFHX4-AS1 silencing exerts an inhibitory effect on breast cancer development by suppressing the activation of the Hippo signaling pathway via FAT4.

[Glycyrrhetinic acid selectively inhibits proliferation of hepatocellular carcinoma cells in vitro].

OBJECTIVE: To investigate the selective inhibitory effect of glycyrrhetinic acid on 4 hepatocellular carcinoma (HCC) cells with different proliferation rates and explore the underlying mechanisms. METHODS: MTT method was used to detect the proliferation rates of 4 HCC cell lines, namely SMMC-7721, SK-HEP1, HEPG2 and HEP3B. Following treatment of the cells with glycyrrhetinic acid (5, 10, 20, 30, 40, and 60 µmol/L), the cell viability was analyzed using MTT assay and the expressions of total ERK protein, p-ERK protein and topoisomerase IIα were detected using Western blotting. RESULTS: Among the 4 cell lines, SMMC-7721 had the lowest and SK-HEP1 had the highest proliferation rate. Treatment with glycyrrhetinic acid for 48 h dose-dependently inhibited the proliferation of all the 4 cell lines in vitro and produced the strongest inhibitory effect in SMMC-7721 cells with the IC50 of 28.04 µmol/L. The proliferation rate of the cells was positively correlated with the expression levels of p-ERK and topoisomerase IIα, which were the lowest in SMMC-7721 cells and the highest in SK-HEP1 cells. Treatment with 50 µmol/L glycyrrhetinic acid significantly down-regulated the expressions of p-ERK and topoisomerase IIα in the 4 HCC cell lines (P<0.05), while 25 µmol/L glycyrrhetinic acid significantly reduced the expression of topoisomerase IIα and p-ERK in SMMC-7721, HEPG2 and HEP3B cells (P<0.05) but not in SK-HEP1 cells. CONCLUSION: Glycyrrhetinic acid can inhibit the proliferation of different HCC cells particularly in cells with a low proliferation rate. The inhibitory effect of glycyrrhetinic acid might be mediated by reducing the expressions of topoisomerase IIα and inhibiting the ERK pathway.

Hundred top-cited articles focusing on acute kidney injury: a bibliometric analysis.

BACKGROUND: Acute kidney injury (AKI) is a major global health issue, associated with poor short-term and long-term outcomes. Research on AKI is increasing with numerous articles published. However, the quantity and quality of research production in the field of AKI is unclear. METHODS AND ANALYSIS: To analyse the characteristics of the most cited articles on AKI and to provide information about achievements and developments in AKI, we searched the Science Citation Index Expanded for citations of AKI articles. For the top 100 most frequently cited articles (T100), we evaluated the number of citations, publication time, province of origin, journal, impact factor, topic or subspecialty of the research, and publication type. RESULTS: The T100 articles ranged from a maximum of 1971 citations to a minimum of 215 citations (median 302 citations). T100 articles were published from 1951 to 2011, with most articles published in the 2000s (n=77), especially the 5-year period from 2002 to 2006 (n=51). The publications appeared in 30 journals, predominantly in the general medical journals, led by New England Journal of Medicine (n=17), followed by expert medical journals, led by the Journal of the American Society of Nephrology (n=16) and Kidney International (n=16). The majority (83.7%) of T100 articles were published by teams involving ≥3 authors. T100 articles originated from 15 countries, led by the USA (n=81) followed by Italy (n=9). Among the T100 articles, 69 were clinical research, 25 were basic science, 21 were reviews, 5 were meta-analyses and 3 were clinical guidelines. Most clinical articles (55%) included patients with any cause of AKI, followed by the specific causes of contrast-induced AKI (25%) and cardiac surgery-induced AKI (15%). CONCLUSIONS: This study provides a historical perspective on the scientific progress on AKI, and highlights areas of research requiring further investigations and developments.

New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer.

Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration-dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC.

Oct-4 is associated with gastric cancer progression and prognosis.

AIM: To investigate the clinical significance of Oct-4 in the development and progression of gastric cancer. METHODS: Immunohistochemistry was used to analyze Oct-4 expression in 412 gastric cancer cases. Oct-4 protein levels were upregulated in gastric cancer tissues compared with adjacent noncancerous tissues. RESULTS: Positive expression of Oct-4 correlated with age, depth of invasion, Lauren classification, lymph node metastasis, distant metastasis, and TNM stage. In stages I, II, and III, the 5-year survival rate of patients with high expression of Oct-4 was significantly lower than that in patients with low expression of Oct-4. In stage IV, Oct-4 expression did not correlate with the 5-year survival rate. Furthermore, multivariate analysis suggested that the depth of invasion, lymph node metastasis, distant metastasis, TNM stage, and upregulation of Oct-4 were independent prognostic factors of gastric cancer. CONCLUSION: Oct-4 protein is a useful marker in predicting tumor progression and prognosis.

Afatinib reverses multidrug resistance in ovarian cancer via dually inhibiting ATP binding cassette subfamily B member 1.

ABCB1-mediated multidrug resistance (MDR) remains a major obstacle to successful chemotherapy in ovarian cancer. Herein, afatinib at nontoxic concentrations significantly reversed ABCB1-mediated MDR in ovarian cancer cells in vitro (p < 0.05). Combining paclitaxel and afatinib caused tumor regressions and tumor necrosis in A2780T xenografts in vivo. More interestingly, unlike reversible TKIs, afatinib had a distinctive dual-mode action. Afatinib not only inhibited the efflux function of ABCB1, but also attenuated its expression transcriptionally via down-regulation of PI3K/AKT and MAPK/p38-dependent activation of NF-κB. Furthermore, apart from a substrate binding domain, afatinib could also bind to an ATP binding domain of ABCB1 through forming hydrogen bonds with Gly533, Gly534, Lys536 and Ala560 sites. Importantly, mutations in these four binding sites of ABCB1 and the tyrosine kinase domain of EGFR were not correlated with the reversal activity of afatinib on MDR. Given that afatinib is a clinically approved drug, our results suggest combining afatinib with chemotherapeutic drugs in ovarian cancer. This study can facilitate the rediscovery of superior MDR reversal agents from molecular targeted drugs to provide a more effective and safer way of resensitizing MDR.

Andrographolide inhibits the migration, invasion and matrix metalloproteinase expression of rheumatoid arthritis fibroblast-like synoviocytes via inhibition of HIF-1α signaling.

AIMS: Hypoxia is implicated in the pathogenesis of rheumatoid arthritis (RA), contributing to the tumor-like phenotypes of RA fibroblast-like synoviocytes (RA-FLSs). Andrographolide is the main bioactive component of Andrographis paniculata, an herbal medicine that shows therapeutic benefits in RA patients. Here, we explored the effects of andrographolide on hypoxia-induced migration and invasion of RA-FLSs. MATERIALS AND METHODS: RA-FLSs were exposed to hypoxia in the presence or absence of andrographolide and cell migration and invasion were tested by Transwell assays. The expression of hypoxia-inducible factor-1 alpha (HIF-1α), matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 was measured by semi-quantitative reverse transcription polymerase chain reaction and Western blot analysis. HIF-1α DNA binding activity was assessed by electrophoretic mobility shift assay. The effects of overexpression of exogenous HIF-1α on the action of andrographolide in RA-FLSs were investigated. KEY FINDINGS: Andrographolide inhibited FLS migration and invasion under hypoxic conditions in a dose-dependent manner. The upregulation of MMP-1, MMP-3 and MMP-9 in response to hypoxia was significantly (P<0.05) attenuated by andrographolide. Moreover, the expression and DNA binding activity of HIF-1α were dose-dependently decreased in andrographolide-treated cells under hypoxic conditions. Overexpression of HIF-1α almost completely reversed the suppressive effects of andrographolide on the migration, invasion and MMP expression of hypoxic RA-FLSs. SIGNIFICANCE: These results indicate the ability of andrographolide to attenuate hypoxia-induced invasiveness of RA-FLSs via inhibition of HIF-1α signaling, and warrant further exploration of andrographolide for the treatment of RA.

Decreased expression of microRNA-130a correlates with TNF-α in the development of osteoarthritis.

OBJECTIVE: Increased expression of tumor necrosis factor a (TNF-α) has emerged as an important inflammatory factor in osteoarthritis (OA) and other joint diseases. The study was performed to investigate whether the expression of TNF-α in human chondrocytes was regulated by miRNAs. METHODS: MiRNA-130a and TNF-α expression in cartilage specimens was examined in patients with knee osteoarthritis, chondrocytes and osteoarthritis rat model. Chondrocytes were transfected with siRNAs as a gene silencing methods. Expression of genes and proteins were analyzed by real-time PCR and western blotting respectively. RESULTS: Increased TNF-α and decreased miRNA-130a were observed in tissues from osteoarthritis patients. Moreover, we found a highly negitive correlation between miRNA-130a and TNF-α. Next, miRNA-130a loss-of-function increased the expression of TNF-α and promoted inflammation in chondrocytes. It was reasonable that miRNA-130a regulated a distinct underlying molecular and pathogenic mechanism of OA by forming a negative feedback loop with TNF-α. Furthermore, there were the abnormalities of bone metabolism in OA rat, which showed the miRNA-130a and TNF-α dysfunction that was one of important factors for the occurrence and development of OA. CONCLUSIONS: Our results indicated that miR-130a played an important role in regulating the expression of TNF-α in human chondrocytes and identified miR-130a as a novel therapeutic target in OA.

Bioavailability enhancement of paclitaxel via a novel oral drug delivery system: paclitaxel-loaded glycyrrhizic acid micelles.

Paclitaxel (PTX, taxol), a classical antitumor drug against a wide range of tumors, shows poor oral bioavailability. In order to improve the oral bioavailability of PTX, glycyrrhizic acid (GA) was used as the carrier in this study. This was the first report on the preparation, characterization and the pharmacokinetic study in rats of PTX-loaded GA micelles The PTX-loaded micelles, prepared with ultrasonic dispersion method, displayed small particle sizes and spherical shapes. Differential scanning calorimeter (DSC) thermograms indicated that PTX was entrapped in the GA micelles and existed as an amorphous state. The encapsulation efficiency was about 90%, and the drug loading rate could reach up to 7.90%. PTX-loaded GA micelles displayed a delayed drug release compared to Taxol in the in vitro release experiment. In pharmacokinetic study via oral administration, the area under the plasma concentration-time curve (AUC0→24 h) of PTX-loaded GA micelles was about six times higher than that of Taxol (p < 0.05). The significant oral absorption enhancement of PTX from PTX-loaded GA micelles could be largely due to the increased absorption in jejunum and colon intestine. All these results suggested that GA would be a promising carrier for the oral delivery of PTX.

Grape seed procyanidin reversal of p-glycoprotein associated multi-drug resistance via down-regulation of NF-κB and MAPK/ERK mediated YB-1 activity in A2780/T cells.

The expression and function of P-glycoprotein (P-gp) is associated with the phenotype of multi-drug resistance (MDR), leading chemotherapy failure of patients suffered with cancer. Grape seed procyanidin(GSP) is a natural polyphenol supplement with anti-inflammatory effect. Present study assessed a new use of GSP on the MDR reversal activity and its possible molecular mechanisms in MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well as, increased the intracellular accumulation of the P-gp substrate rhodamine-123 in A2780/T cells. Nuclear factor-κB(NF-κB) activity, IκB degradation level and NF-κB/p65 nuclear translocation induced by lipopolysaccharide (LPS) and receptor activator for nuclear factor-κB ligand (RANKL) were markedly inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover, the up-regulation of P-gp expression, the activation of AKT/NF-κB and MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared with PDTC and U1026, inhibitor of NF-κB and MAPK/ERK respectively, GSP showed the same tendency of down-regulating NF-κB and MAPK/ERK mediated YB-1 activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and expression of P-gp through down-regulation of NF-κB activity and MAPK/ERK pathway mediated YB-1 nuclear translocation, offering insight into the mechanism of reversing MDR by natural polyphenol supplement compounds. GSP could be a new potential MDR reversal agent used for combination therapy with chemotherapeutics in clinic.

[Effect of L-arginine on pulmonary surfactant and alveolar macrophages in rats with pulmonary injury induced by lipopolysaccharide].

OBJECTIVE: To investigate the effect of L-Arginine (L-Arg) on pulmonary surfactant (PS) expression and alveolar macrophage (AM) in rats with pulmonary injury induced by lipopolysaccharide (LPS). METHODS: Model of acute lung injury (ALI) was made by injection (iv) with LPS 5 mg/kg in rats. Fourty-eight male SD rats were randomly divided into 3 groups(n = 16): control, model (LPS) and L-Arg groups. L-Arg (500 mg/kg ip ,L-Arg group) or saline (control and LPS group) was administrated at 3 h or 6 h after LPS injection respectively for 3 h. The expression of surfactant protein A (SP-A) mRNA in the lung tissue was detected by ISH. The total protein (TP) in the bronchoalveolar lavage fluid (BALF) was detected. Rat AM were isolated from the bronchial alveolar lavage fluid of SD rats and harvested by selective plating technique. LPS and L-Arg were added to the culture medium. The concentration of nitric oxide (NO),the activity of lactate dehydrogenase (LDH), the contents of tumor necrosis factor alpha (TNF-alpha) and interleukin- 6 (IL-6) in the culture supernatants were respectively measured. RESULTS: Compared with the control group, the expression of SP-A mRNA was significantly decreased, the TP concentration was significantly increased in LPS group. Compared with LPS group at the same time points, treatment with L-Arg at 3 h after LPS, the expression of SP-A mRNA in lung tissue was increased markedly, whereas TP concentration was decreased significantly. In cultured rat AM, LDH activity, NO, TNF-alpha and IL-6 contents in culture medium were significantly increased in LPS group to compared with those of control group. LDH activity, TNF-alpha and IL-6 contents were decreased in L-Arg group compared with those of LPS group. CONCLUSION: L-Arg can protect the lung against LPS-induced pulmonary injury by up-regulating the expression of PS and inhibiting inflammatory transmitters from AM.

Comparison of proximal femoral nail antirotation blade and reverse less invasive stabilization system-distal femur systems in the treatment of proximal femoral fractures.

OBJECTIVE: To compare the effects of proximal femoral nail antirotation blade (PFNA) and reverse less invasive stabilization system-distal femur (Liss-DF) systems in the treatment of proximal femoral fractures. METHODS: Between June 2007 and October 2009, 41 proximal femoral fractures were treated, 22 with PFNA (group A) and 19 with reverse LISS-DF plates (group B). The time to starting full weight-bearing, fracture healing time, functional recovery (Parker and Palmer mobility score), neck-shaft angle discrepancies with the intact contralateral hip, preoperative American Society of Anesthesiologists (ASA) scores, the operation durations and amount of intraoperative bleeding were recorded and compared. RESULTS: The mean follow-up period was 11.2 months (range, 10-12 months). Compared with Group A, Group B showed a statistically longer mean time to bear full body weight and heal their fractures, but a smaller neck-shaft angle discrepancy (all P < 0.05). The groups were similar in ASA score, operation duration, amount of intraoperative bleeding and Parker and Palmer mobility score. CONCLUSION: Both PFNA and reverse Liss-DF were satisfactory for the treatment of proximal femoral fractures, but had different advantages. PFNA allowed earlier weight-bearing and accelerated fracture healing. Reverse Liss-DF more effectively avoided coxa vara and may be indicated for patients with very severe osteoporosis.

[Preparation of podophyllotoxin nanostructured lipid carriers and its effects on immortalized human cervical epithelial cells with HPV infection in vitro].

OBJECTIVE: To study the effect of podophyllotoxin nanostructured lipid carriers (POD-NLC) on immortalized human cervical epithelial cells (H8) infected with HPV in vitro. METHODS: POD-NLC was prepared by emulsion evaporation method and characterized using transmission electron microscopy, Zetasizer analyzer and high-performance liquid chromatography (HPLC). H8 cells were treated with different concentrations (0.0001-1 µg/ml) of POD-NLC, free POD, or blank nanostructured lipid carriers (NLC), and the cell proliferation was assessed using MTT assay to evaluate the cytotoxic effects. The changes of cell morphology were observed using fluorescence microscopy, and the cell cycle changes and cell apoptosis were analyzed using flow cytometry. RESULTS: POD-NLC showed a spherical or elliptical shape with good stability in vitro. The average particle size of POD-NLC was 85.6∓10.25 nm, with a Zeta potential of 26.2∓4.1 mV and entrapment efficiency of POD of (88.56∓3.1)%. POD-NLC caused a significant inhibition of H8 cell proliferation in a concentration- and time-dependent manner. At an equivalent concentration, POD-NLC produced a stronger inhibitory effect on cell proliferation than POD. The inhibition rate of H8 cells after a 48-h exposure to POD-NLC and POD reached 95.8% and 65.6%, respectively, and at the highest concentration of 1 µg/ml, the IC(50) of POD-NLC and POD was 0.015 µg/ml and 0.13 µg/ml, respectively. Blank NLC did not obviously affect the proliferation of H8 cells. POD-NLC and POD both caused obvious increases in G(2)/M phase cell percentages and induced typical apoptotic changes of the cells, and their effects were comparable (P>0.05). CONCLUSION: Compared with POD, POD-NLC has more potent effect in inhibiting H8 cell proliferation and inducing cell apoptosis, suggesting its potential in the treatment of cervical HPV infection.

[Effect of imatinib at different concentrations on rat C6 glioma cell apoptosis and cell cycle].

OBJECTIVE: To investigate the effect of imatinib on rat C6 glioma cell apoptosis and cell cycle. METHODS: MTT assay was used to determine the OD value of C6 glioma cells following treatment with imatinib at different concentrations (0.156, 10 and 15 micromo/L) for 24, 48 and 72 h. The cell apoptosis was assayed by Hochest/PI staining and the cell cycle changes were analyzed by flow cytometry. RESULTS: Imatinib treatment resulted in increased number of apoptotic cells in a time- and dose-dependent manner. A 72-h treatment of the cells with imatinib at 10 and 15 micromo/L caused increased cell percentage in G(0)/G(1) phase to (68.53-/+0.83)% and (70.41-/+0.62)%, (P<0.01), decreased the percentage of G(2) phase cells to (14.48-/+0.12)% and (13.84-/+2.86)% (P<0.01), and decreased the percentage of S phase cells to (16.98-/+0.72)% and (15.78-/+2.28)%, respectively (P<0.01). CONCLUSION: Imatinib can induce apoptosis and affect the distribution of the cell cycle of C6 cells in vitro.

[Effects of podophyllotoxin solid lipid nanoparticles on proliferation and apoptosis of cervical carcinoma cells].

OBJECTIVE: To evaluate the anti-proliferative and apoptosis-inducing effect of podophyllotoxin solid lipid nanoparticles (PDP-SLN) in human cervical carcinoma cells in vitro. METHODS: Hela cells were treated with PDP and PDP-SLN at different concentrations (0.0005-5 micromol/L), and the proliferation of the cells was assessed using MTT assay and the apoptotic index was determined by flow cytometry. RESULTS: Both PDP and PDP-SLN showed obvious inhibitory effect on the cell proliferation in a dose- and time-dependent manner. At the same concentration, PDP-SLN produced stronger inhibitory effect on the cells than PDP, with IC50 24, 48, and 72 h after the cell exposure to PDP-SLN and PDP of 4.10, 0.65, 0.20 micromol/L and 9.2, 4.0, 1.3 micromol/L, respectively. Both PDP and PDP-SLN significantly induced the apoptosis of the Hela cell, and the apoptosis rates of the cells incubated in the presence of 0.5 micromol/L PDP-SLN reached 90.8% at 24 h and 94.2% at 72 h, significantly higher than the rate of cells incubated with PDP (64.1% at 24 h and 68.4% at 72 h, P<0.01). CONCLUSION: PDP-SLN can effectively suppress the proliferation and induce apoptosis of Hela cells in vitro.

[Treatment of recurrent condyloma acuminatum with solid lipid nanoparticle gel containing podophyllotoxin: a randomized double-blinded, controlled clinical trial].

OBJECTIVE: To observe the clinical efficacy and safety of podophyllotoxin delivered via solid lipid nanoparticle gel for topic treatment of recurrent condyloma acuminatum. METHODS: In a randomized double-blinded study, podophyllotoxin solid lipid nanoparticles gel and routine podophyllotoxin gel preparation was applied respectively for treatment of 97 volunteer patients with recurrent condyloma acuminatum. The therapeutic effect, condyloma acuminatum relapse following the treatment and adverse effect were evaluated. RESULTS: The wart clearance rate in the condyloma acuminatum patients in the first treatment course with podophyllotoxin solid lipid nanoparticle gel reached 97.1%, close to that with the routine preparation of 90.6%, but the nanoparticle preparation significantly reduced the recurrence rate and adverse effect (P<0.01). CONCLUSION: Podophyllotoxin delivered via solid lipid nanoparticle gel can effectively clear condyloma acuminatum and reduce its recurrence rate with only mild, tolerable adverse effect.

[Arthroscopic surgery on traumatic anterior instability of shoulder].

OBJECTIVE: To study the principle of arthroscopic surgery and its clinical importance on the traumatic anterior shoulder instability. METHODS: From September 2002 to May 2005, 18 patients with injury history of 15 weeks averagely, were involved in the study. Twelve of the patients had a history of sports injuries, 5 had shoulder injuries during working time, and 1 had a traffic accident. Among them, 18 had shoulder pain, 15 had limitation of range of motion (ROM) of shoulder, 18 had positive apprehension test and 5 had positive speed test. Three patients had Hill-Satch lesion in X-ray. Double contrast CT: I degree: 1; II degree: 15; III degree: 2. On arthroscopic view, 18 had anterior glenoid labrum detachment, 4 had anterior capsular laxity, 4 had combined superior labral anterior posterior (SLAP) injury, 3 had free body, 2 had humeral head or glenoid cartilage lesion. Anterior glenoid labrum detachment in 18 patients was reduced and sutured by the fixed anchor technique, 3 had anterior capsule shrinkage, 2 had debridement of frayed long head tendon of biceps, and 2 had reattachment of the long head tendon of biceps outside the capsule. SLAP injuries were sutured in 3 and debridement of frayed superior labrum in 1. RESULTS: All of the patients were followed up with an average of 18 months (10 - 32 months). All the patients felt free of the pain of their shoulder, except one felt shoulder aching after strenuous exercise. The loss of the external-rotation of the operated shoulder was less than 20 degrees in 2 patients and the posterior extension was 10 degrees in 1 patient. One patient had a positive result of Apprehension Sign. UCLA score: 14 +/- 3 preoperatively, 32 +/- 5 postoperatively (t = 14.081, P < 0.01). All patients returned to pre-injured sports activities and original work. CONCLUSIONS: Traumatic anterior shoulder instability can obtain good effects when treated with the arthroscopic surgery of shoulder. Complete reduction, and reliable fixation of the anterior glenoid labrum complex is the key point. Fixation with the suture anchor is reliable and makes the operation simple.

[Preparation of stearic acid solid lipid nanoparticles containing podophyllotoxin].

OBJECTIVE: To improve the therapeutic efficacy and reduce the adverse effect of podophyllotoxin (PPT) by wrapping it in stearic acid solid lipid nanoparticles. METHODS: Stearic acid solid lipid nanoparticles containing podophyllotoxin was prepared using modified microemulsion technique, whose morphology was examined by transmission electron microscope. High-performance of liquid chromatography was employed to determine the entrapment efficiency of PPT in the nanoparticles. RESULT: The entrapment efficiency of PPT in the nanoparticles was 85.6% and the mean diameter of the particles was 56.5+/-25.8 nm. CONCLUSION: The stearic acid solid lipid nanoparticles has high entrapment efficiency for PPT and is homogeneous in size, which can be a promising targeted preparation for epidermal delivery.

Studies on the effects of fpf1 gene on Artemisia annua flowering time and on the linkage between flowering and artemisinin biosynthesis.

The flowering promoting factor1 ( fpf1) from Arabidopsis thaliana was transferred into Artemisia annua L. via Agrobacterium tumefaciens. The fpf1 gene was firstly inserted in the binary vector pBI121 under the control of CaMV 35S promoter to construct the plant expression vector pBIfpf1, then leaf explants of A. annua were infected with A. tumefaciens LBA4404 containing pBIfpf1, and induced shoots. Transgenic plants were obtained through the selection with kanamycin. PCR, PCR-Southern and Southern blot analyses confirmed that the foreign fpf1 gene had been integrated into the A. annua genome. RT-PCR and RT-PCR-Southern analyses suggested that the foreign fpf1 gene had expressed at the transcriptional level. Under short-day conditions, the flowering time of fpf1 transgenic plants was about 20 days earlier than the non-transformed plants; however, no significant differences were detected in artemisinin content between the flowering transgenic plants and the non-flowering non-transgenic plants. These results showed that flowering is not a necessary factor for increasing the artemisinin content, furthermore, there may be no direct linkage between flowering and artemisinin biosynthesis.