Acylphloroglucinol-monoterpene meroterpenoids from Eucalyptus tereticornis and their inhibitory activity against ATP citrate lyase.

Five undescribed enantiomeric pairs of acylphloroglucinol-monoterpene meroterpenoids ((+)-/(-)-eucateretins A-E) resolved by chiral-phase HPLC were obtained from the leaves of Eucalyptus tereticornis Smith, along with nine known analogues. Their structures were elucidated by spectroscopic methods and ECD calculations. This is the first report of meroterpenoid enantiomers from this plant. Some of the isolates, (-)-eucateretin A, (+)-/(-)-eucateretins E, 7'α-eucalrobusone X, eucalrobusone X, and robustadial B, exhibited inhibitory effects on ATP citrate lyase, and 7'α-eucalrobusone X significantly suppressed the hepatocyte lipogenesis.

Letrozole + Ziwu Liuzhu Transcutaneous Electrical Acupoint Stimulation Improves Ovulation-Induced Pregnancy Rate in Obese Women with Polycystic Ovary Syndrome: A Prospective Cohort Study.

Objective: This study investigated the effect of letrozole with/without meridian-infusion percutaneous electrical stimulation on the rates of ovulation-induced pregnancy in patients with obese polycystic ovary syndrome (obPCOS). Materials and Methods: Patients with obPCOS, ages 20-40, each with a body mass index (BMI) ≥24 kg/m2, and/or waist circumference ≥80 cm, and at least 1 side tubal patency were enrolled at the Guangdong Women and Children Hospital, Guangzhou, China. They were divided into 2 groups: ZLT [Ziwu Liuzhu + transcutaneous electrical acupoint stimulation] and control. Baseline conditions and pregnancy status were collected for all patients. Multivariate Cox regression analysis and sensitivity analysis of propensity score matching (PSM) were performed for the groups after multiple interpolations. Results: From July 2021 to September 2022, 345 patients with obPCOS were recruited: 53 cases/69 cycles in the ZLT group and 292 cases/396 cycles in the control group. The 2 sets of baselines were flush. The anovulatory cycle rates were: ZLT, 2.89% (2/69); and control, 1.77% (7/396); P > 0.05. Multifollicle growth-cycle rates were: ZLT, 0% (0/69); and control, 0.76% (3/396); P > 0.05. Multivariate COX regression analysis showed adjusted hazard ratio (aHR) 95% confidence interval (CI): 2.11 (1.19, 3.73); P = 0.011. Multivariate Cox regression analysis with multiple imputation showed aHR 95% CI: 2.11 (1.19, 3.73); P = 0.013. In the overweight group (24-28 kg/m2), the pregnancy rate of the control and ZLT groups were 20.2% and 32.3%, respectively, aHR 95% CI: 1.76 (0.87,3.55); P = 0.113. In the obese cohort (≥ 28 kg/m2), the control and ZLT groups, pregnancy rates were 10.7% and 27.3%, respectively, aHR 95% CI: 3.46 (1.21, 9.92); P = 0.021; (Pfor interaction = 0.369). The caliper value was set as 0.2 for BMI and antral-follicle count, and PSM was performed at 1:1, aHR 95%CI: 2.45 (1.01, 5.96); P = 0.048. Conclusions: Letrazole + ZLT had a positive effect on ovulation-induced pregnancy rates in patients with obPCOS.

Evaluation of short-term (16-week) effectiveness and safety of guselkumab in patients with psoriasis: A prospective real-life study on the Chinese population.

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

Prevalence and risk factors of severe postpartum hemorrhage: a retrospective cohort study.

BACKGROUND: Although maternal deaths are rare in developed regions, the morbidity associated with severe postpartum hemorrhage (SPPH) remains a major problem. To determine the prevalence and risk factors of SPPH, we analyzed data of women who gave birth in Guangzhou Medical Centre for Critical Pregnant Women, which received a large quantity of critically ill obstetric patients who were transferred from other hospitals in Southern China. METHODS: In this study, we conducted a retrospective case-control study to determine the prevalence and risk factors for SPPH among a cohort of women who gave birth after 28 weeks of gestation between January 2015 and August 2019. SPPH was defined as an estimated blood loss ≥1000 mL and total blood transfusion≥4 units. Logistic regression analysis was used to identify independent risk factors for SPPH. RESULTS: SPPH was observed in 532 mothers (1.56%) among the total population of 34,178 mothers. Placenta-related problems (55.83%) were the major identified causes of SPPH, while uterine atony without associated retention of placental tissues accounted for 38.91%. The risk factors for SPPH were maternal age < 18 years (adjusted OR [aOR] = 11.52, 95% CI: 1.51-87.62), previous cesarean section (aOR = 2.57, 95% CI: 1.90-3.47), history of postpartum hemorrhage (aOR = 4.94, 95% CI: 2.63-9.29), conception through in vitro fertilization (aOR = 1.78, 95% CI: 1.31-2.43), pre-delivery anemia (aOR = 2.37, 95% CI: 1.88-3.00), stillbirth (aOR = 2.61, 95% CI: 1.02-6.69), prolonged labor (aOR = 5.24, 95% CI: 3.10-8.86), placenta previa (aOR = 9.75, 95% CI: 7.45-12.75), placenta abruption (aOR = 3.85, 95% CI: 1.91-7.76), placenta accrete spectrum (aOR = 8.00, 95% CI: 6.20-10.33), and macrosomia (aOR = 2.30, 95% CI: 1.38-3.83). CONCLUSION: Maternal age < 18 years, previous cesarean section, history of PPH, conception through IVF, pre-delivery anemia, stillbirth, prolonged labor, placenta previa, placental abruption, PAS, and macrosomia were risk factors for SPPH. Extra vigilance during the antenatal and peripartum periods is needed to identify women who have risk factors and enable early intervention to prevent SPPH.

Potential of utilization of albumin as a delivery module in cancer model.

PURPOSE: This study compared the potential of 2 nanoparticles, namely albumin and gold nanoparticles, for the specific delivery of 99mTC- resveratrol in colon cancer. The aim of adding radioactive tag (99mTC) to resveratrol was to utilize it for imaging purposes. METHODS: We compared the potential of albumin loaded 99mTC- resveratrol with gold nanoparticles loaded 99mTc-resveratrol for tumor specific delivery. Twenty male Wistar rats were used for the formation of colon cancer model. Both delivery molecules were tested for tumor specific delivery. RESULTS: The results showed efficient delivery of 99mTC-resveratrol with albumin in comparison to gold nanoparticles, as confirmed by single-photon emission computed tomography (SPECT). CONCLUSIONS: Albumin is a superior molecule for the efficient delivery of 99mTC- resveratrol at tumor sites in comparison to gold nanoparticles.

[Quality characterization analysis of single decoction and merger decoction of Baihu and Guizhi].

To study the differences and similarities in pharmaceutical characterization and pharmacodynamic characterization between the single decoction and merger decoction of Baihu and Guizhi. The same technology parameters were used to prepare Baihu and Guizhi single decoticon and merger decoction extracts, and then the differences and similarities in pharmaceutical characterization were analyzed based on their HPLC fingerprint, content of index components, and the extraction content. The pharmacodynamic differences and similarities were analyzed by inflammatory model and pain model. There was no significant difference in HPLC chromatographic peak, but the peak area value reflected the difference of quantity to some extent. It was found that the peak value of single Rhizoma anemarrhenae and Cassia twig decoction was less than the peak of their merger decoction, but the peak value of single honey-fried Licorice root decoction was greater than the peak of merger decoction． The contents of neomangiferin, mangiferin and timosaponin B Ⅱ among index components as well as extraction content in merger decoction were higher than those in single decoction． The contents of liquiritin and glycyrrhizic acid as well as extraction content in merger decoction were lower than those in single decoction． There was no significant difference in the content of cinnamicacid and its extraction content between merger decoction and single decoction. According to the efficacy experiment, both of them showed significant anti-inflammatory and analgesic effects. However, the merger decoction showed faster anti-inflammation effect, and longer analgesic effect. It can be concluded that the merger decoction and single decoction of Baihu and Guizhi have the same material basis, and the merger decoction is better for the dissolution of the active ingredients in this recipe, and is more beneficial to the therapeutic effect.

[Effect of serum containing Xihuang pill on proliferation of human breast cancer cell line MDA-MB-435 and MCF-7 Cells].

To study the effect of serum containing Xihuang pill on the proliferation of human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of Xihuang pill in resisting breast cancer. The serum of the rats was prepared by the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT-PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were detected by immunofluorescence. The rats with serum containing Xihuang pill could inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (P<0.05). The serum containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (P<0.05), and the ratio of Bcl-2/Bax was decreased (P<0.05). Meanwhile, the serum containing Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and decrease the expression of Bcl (P<0.05), but there was no significant difference between the expression of TP53mRNA and Bax protein expressions after the treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill can induce the apoptosis of human breast cancer cells, and the mechanism of estrogen receptor-negative breast cancer cell apoptosis may be induced by up-regulating the mRNA expression of TP53, which can induce the expression of Bax and promote the metastasis of Bax to mitochondria, and ultimately play the role of inducing apoptosis.

Effects of hyperbaric oxygen on hippocampal neuronal apoptosis in rats with acute carbon monoxide poisoning.

INTRODUCTION: Acute carbon monoxide (CO) poisoning causes serious health problems such as neuropsychological sequelae. This study aimed to investigate neuronal apoptosis and the effects of hyperbaric oxygen (HBO2) on different regions of the rat hippocampus after CO poisoning. METHODS: 90 mature male Sprague Dawley rats were randomly divided into three groups: the normal control group (NC group), the acute carbon monoxide-poisoned group (CO group) and the hyperbaric oxygen treatment group (HBO2 group). CO exposure included 0, 1, 3, 7, 14 and 21 treatment days, one exposure on the first day, and sacrifice on each of the following days. HBO2 exposure included treatment for 0, 1, 3, 7, 14 and 21 days, daily treatment after CO exposure, and sacrifice after the last HBO2 treatment on each of those days. Hematoxylin-eosin staining, immunohistochemical staining, immunofluorescence staining, and western blot analysis were performed to detect apoptosis in brain tissue samples. RESULTS: MMP-9 and caspase-3 were prominently increased by CO exposure and inhibited by HBO2 in the CA3 region in the hippocampus at one, three and seven days (immunohistochemical staining [IHC]: P ⟨ 0.05). Neu N and the ratio of Bcl-2/ BAX were prominently decreased by CO exposure and rescued by HBO2 in the CA3 region after seven days of treatment (IHC: P ⟨ 0.05). CONCLUSION: These findings indicated that neuronal apoptosis in the rat hippocampus could be induced by acute CO exposure, especially in the CA3 region. HBO2 could effectively inhibit neuronal apoptosis, especially in the CA3 region after seven days of treatment. The application of HBO2 to inhibit MMP-9 and apoptosis may contribute to brain recovery after acute CO poisoning.

BDNF-GSK-3ß-ß-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects of Morinda officinalis Oligosaccharides in Rats.

Background: Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear. Methods: Chronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3ß in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3ß, ß-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot. Results: We found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3ß by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3ß, and ß-catenin in the medial prefrontal cortex. Conclusion: Our findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3ß-ß-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.

Design, synthesis and cytotoxic activities of novel 2,5-diketopiperazine derivatives.

A series of novel N-1-monoallylated 2,5-diketopiperazine derivatives were designed, synthesized, and evaluated as cytotoxic agents against eight cancer cell lines by using CCK8 assay. These derivatives were substituted with methoxyphenyl groups at C-6 position, and various long alkyl side chains at C-3-position of the 2,5-diketopiperazine ring. The cytotoxic results showed that 4-methoxyphenyl group was better than 2-methoxyphenyl group as optimal substitutive group, while 3-methoxyphenyl group was not a suitable one. When the number (n value) of the methylene groups for the long alkyl side chain was 3 (compounds 1c and 3c), the derivatives had the strongest cytotoxicities. Compound 3c substituted with 4-methoxyphenyl group and pentylidene side chain exhibited strong activity (IC50 = 0.36-1.9 µM) against all cancer cell lines, and could obviously induce apoptosis of cancer cell line U937 at 1.0 µM after 48 h treatment.

ROS-Induced Nuclear Translocation of Calpain-2 Facilitates Cardiomyocyte Apoptosis in Tail-Suspended Rats.

Isoproterenol (ISO) induced nuclear translocation of calpain-2 which further increased susceptibility of cardiomyocyte apoptosis in tail-suspended rats. The underlying mechanisms remain elusive. In the present study, the results showed that ISO (10 nM) significantly elevated NADPH oxidases (NOXs) activity and NOXs-derived ROS productions which induced nuclear translocation of calpain-2 in cardiomyocytes of tail-suspended rats. In contrast, the inhibition of NADPH oxidase or cleavage of ROS not only reduced ROS productions, but also resisted nuclear translocation of calpain-2 and decreased ISO-induced apoptosis of cardiomyocyte in tail-suspended rats. ISO also increased the constitutive binding between calpain-2 and Ca(2+)/calmodulin-dependent protein kinase II δB (CaMK II δB) in nuclei, concomitant with the promotion of CaMK II δB degradation and subsequent down-regulation of Bcl-2 mRNA expression and the ratio of Bcl-2 to Bax protein in tail-suspended rat cardiomyocytes. These effects of ISO on cardiomyocytes were abolished by a calpain inhibitor PD150606. Inhibition of calpain significantly reduced ISO-induced loss of the mitochondrial membrane potential, cytochrome c release into the cytoplasm, as well as the activation of caspase-3 and caspase-9 in mitochondrial apoptotic pathway. In summary, the above results suggest that ISO increased NOXs-derived ROS which activated nuclear translocation of calpain-2, subsequently nuclear calpain-2 degraded CaMK II δB which reduced the ratio of Bcl-2 to Bax, and finally the mitochondria apoptosis pathway was triggered in tail-suspended rat cardiomyocytes. Therefore, calpain-2 may represent a potentially therapeutic target for prevention of oxidative stress-associated cardiomyocyte apoptosis.

Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation.

AIMS: Increased fructose consumption predisposes the liver to nonalcoholic fatty liver disease (NAFLD), but the mechanisms are elusive. Thioredoxin-interacting protein (TXNIP) links oxidative stress to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation and this signaling axis may be involved in fructose-induced NAFLD. Here, we explore the role of reactive oxygen species (ROS)-induced TXNIP overexpression in fructose-mediated hepatic NLRP3 inflammasome activation, inflammation, and lipid accumulation. RESULTS: Rats were fed a 10% fructose diet for 8 weeks and treated with allopurinol and quercetin during the last 4 weeks. Five millimolars of fructose-exposed hepatocytes (primary rat hepatocytes, rat hepatic parenchymal cells [RHPCs], HLO2, HepG2) were co-incubated with antioxidants or caspase-1 inhibitor or subjected to TXNIP or NLRP3 siRNA interference. Fructose induced NLRP3 inflammasome activation and pro-inflammatory cytokine secretion, janus-activated kinase 2/signal transducers and activators of transcription 3-mediated inflammatory signaling, and expression alteration of lipid metabolism-related genes in cultured hepatocytes and rat livers. NLRP3 silencing and caspase-1 suppression blocked these effects in primary rat hepatocytes and RHPCs, confirming that inflammasome activation alters hepatocyte lipid metabolism. Hepatocellular ROS and TXNIP were increased in animal and cell models. TXNIP silencing blocked NLRP3 inflammasome activation, inflammation, and lipid metabolism perturbations but not ROS induction in fructose-exposed hepatocytes, whereas antioxidants addition abrogated TXNIP induction and diminished the detrimental effects in fructose-exposed hepatocytes and rat livers. INNOVATION AND CONCLUSIONS: This study provides a novel mechanism for fructose-induced NAFLD pathogenesis by which the ROS-TXNIP pathway mediates hepatocellular NLRP3 inflammasome activation, inflammation and lipid accumulation. Antioxidant-based interventions can inhibit the ROS-TXNIP pathway.

[A new neolignan from fruit of Solanum torvum].

One new neolignan identified as 2, 3-( trans) -dihydro-2-(4-hydroxy-3-methoxyphenyl) -3-[(beta-D-glucopyranosyloxy) methyl]-7-methoxybenzofuran-5-propenoic acid (1) and five known steroidal glycosides namely torvoside A(2), torvoside C(3), torvoside H(4), solanolactoside A (5), (25S)-6alpha-hydroxy-5alpha-spirostan-3-one-6-0-[alpha-L-rhamnopyranosyl-(1-->3-beta3)-beta-D-D-quinovopyr-anoside] (6) were isolated from the fruits of Solanum torvum. Their structures were elucidated on the basis of 1D, 2D NMR and MS spectroscopic analysis.

Reduction of prostate intrafractional motion from shortening the treatment time.

This study aims to quantify the reduction of the intrafractional motion when the prostate intensity modulated radiation therapy (IMRT) treatment time is shortened. Prostate intrafractional motion data recorded by the Calypso system for 105 patients was analyzed. Statistical distributions of the prostate displacements for the regular IMRT treatment and the first 1, 2, 3 and 5 min of the treatment were calculated and used for treatment margin estimation for all the selected patients. The treatment margins estimated for the first 1, 2, 3 and 5 min were compared with those for the regular IMRT treatment to quantify the reduction of the motion. If the treatment can be completed within 5 (3) min, the standard deviation of the prostate displacement could be reduced by up to 45% and the required treatment margins could be reduced to 1.2 (1.1), 0.9 (0.8), 2.2 (1.9), 1.9 (1.5), 1.9 (1.7) and 2.8 (2.4) mm from 1.5, 1.1, 2.8, 3.0, 2.4 and 3.9 mm in the left, right, superior, inferior, anterior and posterior directions, respectively. The same work was also performed for 19 of the 105 patients who exhibited the largest motion with 30% of their treatment time having 3D motion more than 3 mm. For this group of patients, the required margins change to 1.4 (1.2), 0.8 (0.8), 1.8 (1.6), 2.3 (1.8), 1.7 (1.5) and 3.4 (2.8) mm from 1.9, 1.2, 1.7, 3.7, 1.6 and 4.9 mm in the six directions when the treatment time is reduced to 5 (3) min. The intrafractional motion effects on prostate treatment are significantly smaller and the required margins can be therefore reduced when the treatment is shortened.

Decrease of renal aquaporins 1-4 is associated with renal function impairment in pediatric congenital hydronephrosis.

BACKGROUND: Renal aquaporins (AQP1-4) concentration is downregulated and is in proportion to the degree of hydronephrosis graded by ultrasound in pediatric congenital hydronephrosis (CH). However, the relationship between the expression of AQP1-4 with the changes of renal function impairment (RFI) evaluated by (99m)Tc-DTPA renal dynamic imaging is still unclear. This study aimed to investigate the relationship between AQP1-4 expression and degree of RFI in children with CH. METHODS: The expression of AQP1-4 was evaluated in 45 children with unilateral ureteropelvic junction obstruction (28 boys and 17 girls, average age: 28±10 months) and 15 children undergoing nephrectomy for nephroblastoma (8 boys and 7 girls, average age: 26±8 months) by immunoblotting and immunohistochemistry. Renal function was graded into mild and severe RFI by (99m)Tc-DTPA renal dynamic imaging. RESULTS: One-way analysis of variance with Bonferonni's correction showed a significantly reduced protein expression of AQP1-4 in the severe RFI group compared with those in both mild RFI group and controls (AQP1: 0.52±0.09 vs. 0.91±0.06 vs. 1.23±0.033; AQP2: 0.68±0.12 vs. 1.09±0.06 vs. 1.52±0.08; AQP3: 0.59±0.16 vs. 0.94±0.08 vs. 1.31±0.07; AQP4: 0.64±0.06 vs. 1.14±0.07 vs. 1.61±0.07; P<0.001, respectively). In kidneys with severe RFI, there was a reduction in the protein concentration of all four AQP isoforms which was more pronounced compared with those seen in kidneys with mild RFI and in the controls. CONCLUSION: AQP1-4 expression is reduced in proportion with the impairment degree of renal function graded by (99m)Tc-DTPA renal dynamic imaging in human CH.

[Application of the vacuum sealing drainage technique combined with skin flap in chronic ulcerative wounds].

OBJECTIVE: To explore the feasibility and efficacy of the vacuum sealing drainage (VSD) technique combined with skin flap for the treatment of chronic ulcerative wounds. METHODS: From June 2009 to Aug. 2011, the VSD technique combined with skin flap has been applied in the treatment of 15 patients with chronic ulcerative wounds caused by various reasons. The VSD was applied to the wound for 1-6 times. When infection was controlled and fresh granulation grew, skin flap was used to cover the wound. RESULTS: Flap necrosis happened in a small area at the distal end in one case, which healed after skin graft. All the other flaps survived with primary healing. The patients were followed up for 6-24 months postoperatively with no recurrence of infection. CONCLUSIONS: VSD combined with skin flap is an ideal choice for reconstruction of chronic ulcerative wounds. It has the advantages of low complications, reliable flap survival rate, and low infection recurrence.

Activation of BK(Ca) channels in zoledronic acid-induced apoptosis of MDA-MB-231 breast cancer cells.

BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro.

Uncertainties in IMRT dosimetry.

PURPOSE: The purpose of this study is to investigate some characteristics of the beam delivery system and their effects on the dose distribution of intensity-modulated radiation therapy (IMRT) and the results of patient-specific IMRT quality assurance (QA). These characteristics include the accelerator source distribution and multileaf collimator (MLC) geometry. METHODS: Monte Carlo dose calculations based on intensity maps that were built from the actual deliverable IMRT leaf sequences with and without considering the characteristics of the beam delivery system were performed in this study using in-house Monte Carlo software. The effect of the resolution of the intensity maps on the dose distribution was investigated first. The mean dose of the treatment target and the voxel doses in the high dose region of seven IMRT plans generated by different treatment planning systems for Varian 21EX and Siemens Primus linear accelerators were used for comparison and evaluation. RESULTS: The results show that a 0.2 x 0.2 mm2 or smaller pixel size is needed for the intensity maps for accurate IMRT dose calculation. The extrafocal source, MLC leaf thickness, leakage, tongue-and-groove structure, and the effective leaf offset can affect the mean dose by up to 1.5%, 4.5%, 5.6%, 5.3%, and 7.8%, respectively, when these factors are considered separately. They also cause significant uncertainties to the voxel dose with standard deviations up to 2.5%, 0.7%, 2.1%, 1.3%, and 5%, respectively. The overall effect on the mean dose is up to 8% and the standard deviation of the voxel dose uncertainty is up to 6.4% when all the effects are included. The maximum standard deviation is reduced to 4.6% if the voxel size of the dose calculation matrix is increased from 0.04 to 0.3 cm3 to make it comparable with the sensitive volume of the ionization chamber used for IMRT QA measurements. CONCLUSIONS: It can be concluded that the characteristics of the beam delivery system are the major contributors to the uncertainty of measurement-based IMRT QA because most of them are not fully considered in the currently available treatment planning systems.

[Repair of the large skin and vessel defect of upper arm with free anterolateral thigh flap].

OBJECTIVE: To explore an effective method for repairing the large skin and vessel defect of upper arm. METHODS: The large skin defect was repaired by the free anterolateral thigh flap. The vessel defect was reconstructed with the end branch of descending branch from lateral femoral circumflex artery, or the large muscular branch through bridge-like vascular anastomosis. RESULTS: Since 2003, 5 cases were treated. All the flaps survived completely with a soft tissue texture. They were followed up for 8-24 months. The cosmetic and functional results were both satisfactory with less morbidity in the donor sites. The blood supply of the flap and the end of extremities was not affected by weather. CONCLUSIONS: Anterolateral thigh flap is very suitable for large skin and vessel defect of upper arm.

Gains from real-time tracking of prostate motion during external beam radiation therapy.

PURPOSE: To study the gains from real-time tracking of prostate motion and threshold-based intervention and the feasibility of margin reduction for external beam radiation therapy of prostate cancer. METHODS AND MATERIALS: Prostate intrafractional motion data from 775 randomly selected treatment fractions (105 prostate patients) were analyzed. Statistical distributions of prostate intrafractional displacement from baseline were used for treatment margin calculation together with other geometrical uncertainties for all patients and a subset of 7 patient who exhibited the largest intrafractional motion. Compared with treatment without any intrafractional intervention, potential reductions in treatment margins were evaluated for treatments with 5-mm and 3-mm threshold-based intervention and four-dimensional (4D) treatments with and without prostate rotation correction. RESULTS: The percentage of time of prostate displacement from the baseline by 3 mm and 5 mm in any direction was 13.4% and 1.8%, respectively, for the general patient population. The ratios were 41% and 15% for the 7 selected patients. Reductions in the posterior margin were 0.2, 0.5, 1.3, and 3.1 mm from the original 7.7 mm, respectively, for 5-mm and 3-mm threshold-based treatments and 4D treatments with and without prostate rotation correction for all patients. They were 1.3, 1.9, 3.1 and 4.9 mm from the original 9.5 mm, corresponding to the 7 selected patients. The treatment margin reductions in other directions were even smaller. CONCLUSIONS: Real-time motion tracking and threshold-based intrafractional intervention may play a significant roll in treatment margin reduction for a small fraction of patients but not for the general patient population. Four-dimensional treatments with prostate rotation correction can reduce the treatment margin more significantly.