Hypoxic adipose stem cell-derived exosomes carrying high-abundant USP22 facilitate cutaneous wound healing through stabilizing HIF-1α and upregulating lncRNA H19.

Hypoxic preconditioning has been recognized as a promotive factor for accelerating cutaneous wound healing. Our previous study uncovered that exosomal lncRNA H19, derived from adipose-derived stem cells (ADSCs), plays a crucial role in orchestrating cutaneous wound healing. Herein, we aimed to explore whether there is a connection between hypoxia and ADSC-derived exosomes (ADSCs-exos) in cutaneous wound healing. Exosomes extracted from ADSCs under normoxic and hypoxic conditions were identified using transmission electron microscope (TEM) and particle size analysis. The effects of ADSCs-exos on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8, EdU, wound healing, and tube formation assays. Expression patterns of H19, HIF-1α, and USP22 were measured. Co-immunoprecipitation, chromatin immunoprecipitation, ubiquitination, and luciferase reporter assays were conducted to confirm the USP22/HIF-1α/H19 axis, which was further validated in a mice model of skin wound. Exosomes extracted from hypoxia-treated ADSCs (termed as H-ADSCs-exos) significantly increased cell proliferation, migration, and angiogenesis in H2O2-exposed HUVECs, and promoted cutaneous wound healing in vivo. Moreover, H-ADSCs and H-ADSCs-exos, which exhibited higher levels of H19, were found to be transcriptionally activated by HIF-1α. Mechanically, H-ADSCs carrying USP22 accounted for deubiquitinating and stabilizing HIF-1α. Additionally, H-ADSCs-exos improved cell proliferation, migration, and angiogenesis in H2O2-triggered HUVECs by activating USP22/HIF-1α axis and promoting H19 expression, which may provide a new clue for the clinical treatment of cutaneous wound healing.

The efficacy and safety of apatinib plus capecitabine in platinum-refractory metastatic and/or recurrent nasopharyngeal carcinoma: a prospective, phase II trial.

BACKGROUND: Previous studies have shown that monotherapy with apatinib, an oral tyrosine kinase inhibitor, has promising efficacy for treating recurrent or metastatic (RM) nasopharyngeal carcinoma (NPC) patients. In this study, we aimed to assess the efficacy and safety of apatinib combined with capecitabine as a second-line therapy or beyond for treating RM-NPC patients who failed the first-line platinum-based chemotherapy. METHODS: In this single-arm, phase II study, we enrolled RM-NPC patients who had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The sample size was determined using Simon's two-stage design. All patients were administered with apatinib 500 mg once daily and capecitabine 1000 mg/m2 twice per day on days 1-14 of each 21-day cycle. The primary endpoint was the objective response rate (ORR), and the secondary endpoints comprised disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: We enrolled 64 patients from September 2018 to August 2020. The ORR and DCR were 39.1% (95% CI, 27.1-52.1) and 85.9% (95% CI, 75.0-93.4), respectively. The median DoR was 14.4 months (95% CI, 7.8-21.0). As of April 20, 2021, the median follow-up duration was 12.0 months. The median PFS was 7.5 months (95% CI, 5.0-10.0) and the median OS was 15.7 months (95% CI, 11.3-20.1). The most common toxicities of any grade were anemia (75.0%), hand-foot syndrome (65.6%), and proteinuria (64.0%). Grade 3-4 toxicities were observed in 36 (56.3%) patients, with hypertension (14.1%), mucositis (12.4%), and fatigue (10.9%) most commonly observed. CONCLUSIONS: Apatinib plus capecitabine shows promising efficacy as a second-line treatment option in pretreated platinum-refractory RM-NPC patients. Dose selection of this combination needs further investigation considering the toxicity. TRIAL REGISTRATION: Chi-CTR1800017229.

A therapeutic role of exosomal lncRNA H19 from adipose mesenchymal stem cells in cutaneous wound healing by triggering macrophage M2 polarization.

BACKGROUND: Emerging evidence has figured out that adipose mesenchymal stem cells (ADSCs) promote wound healing. Exosomes, which act as main paracrine factors and contains various protein, lncRNA, and miRNAs, play a critical role in wound healing. Nevertheless, the mechanism remains to be elucidated. This study aims to identify the underlying mechanism of ADSCs-derived exosome (ADSCs-exos)-mediated wound healing. METHODS: ADSCs-exos were characterized using the transmission electron microscope, dynamic light scattering, and western blot. ELISA, RT-qPCR, flow cytometry, western blot, CCK-8 assay, transwell assay and tube formation were employed to validate the actions of ADSCs-exos harboring H19 in cell polarization, proliferation, migration and angiogenesis. The regulatory axis among H19, miR-130b-3p and PPARγ or STAT3 was confirmed by RNA pull-down, RIP assay and dual-luciferase reporter assays. RESULTS: ADSCs-exos harboring H19 promoted macrophage M2 polarization, thereby enhancing fibroblast proliferation, migration and endothelial cell angiogenesis. However, their promotive effects were disrupted within H19 depletion in ADSCs-exos. Additionally, miR-130b-3p, directly targeting PPARγ or STAT3, was identified to be a downstream effector to participate in H19-mediated biological effects. Moreover, ADSCs-exos carrying H19 modulated cutaneous wound healing via H19/miR-130b-3p -mediated macrophage M2 polarization in vivo. CONCLUSION: Collectively, ADSCs-derived exosomal H19 accelerates cutaneous wound healing via the miR-130b-3p/PPARγ/STAT3 axis, indicating potential therapeutic strategies for the treatment of wound healing.

LncRNA MALAT1 from human adipose-derived stem cell exosomes accelerates wound healing via miR-378a/FGF2 axis.

Aim: The effects of MALAT1 from human adipose-derived stem cell (ADSC) exosomes in skin wound healing were investigated. Material & methods: The viability, apoptosis and migration ability of human skin fibroblasts (HSFs) were evaluated by Cell Counting Kit-8 assay, flow cytometry and scratch assay, respectively. A mouse model was established to evaluate the role of exosomal MALAT1 in skin wound healing in vivo. Results: Human ADSC exosomes promoted the proliferation and migration of HSFs and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited HSF viability and migration, promoted HSF apoptosis and inhibited angiogenesis by upregulating miR-378a. Overexpression of miR-378a inhibited the migration and proliferation of HSFs by downregulating FGF2 expression. ADSC exosomes promoted skin wound healing by mediating MALAT1 in vivo. Conclusion: Exosomal MALAT1 accelerated skin wound healing by regulating the miR-378a/FGF2 axis, suggesting that MALAT1 might be used as a potential target for cutaneous wound treatment.

Skin wound healing is a process of synergistic action of multiple factors. Adipose-derived stem cells (ADSCs), a group of stem cells, are recruited into damaged tissues and secret several cytokines, which promote nascent tissue formation. ADSC-derived exosomes play crucial roles in wound healing as a paracrine vehicle for delivering chemokines, growth factors and RNAs to host cells. LncRNAs are involved in multiple physiological processes, including tissue repair. Furthermore, lncRNA MALAT1 is associated with endothelial cell migration and angiogenesis in different types of diseases. This study demonstrated that hADSC exosomes promoted the proliferation and migration of human skin fibroblasts and increased MALAT1 expression. MALAT1 silencing in human ADSCs inhibited human skin fibroblast viability and migration, promoted apoptosis and suppressed angiogenesis by upregulating miR-378a. miR-378a overexpression inhibited the phenotypic characteristics of human skin fibroblasts by downregulating FGF2. Exosomal MALAT1 appeared to accelerate skin wound healing by mediating the miR-378a/FGF2 axis.

Exosomal microRNA-125a-3p from human adipose-derived mesenchymal stem cells promotes angiogenesis of wound healing through inhibiting PTEN.

Angiogenesis plays a key in the process of tissue repair and wound healing. Human adipose-derived mesenchymal stem cells (HADSCs) have been found to act a promotion role during angiogenesis. Moreover, miR-125a-3p in HADSCs could promote the angiogenesis of HUVECs, but their specific mechanism in wound healing needs further study. Western blotting and qRT-PCR were used for detecting the protein and mRNA level, respectively. Exosomes were isolated successfully, and transmission electron microscope was used to identify exosomes. Angiogenesis, cell migration, and proliferation were detected with tube formation, wound healing, and MTT assays. The interactions of miR-125a-3p and PTEN were validated using dual-luciferase reporter assay. Animal model was used to evaluate the effect of miR-125a-3p on wound healing. HADSCs-exosome remarkably promoted the viability, migration, and angiogenesis of HUVECs. Knockdown of miR-125a-3p in HADSCs could inhibit the effect of HADSCs-exosome, while overexpression of miR-125a-3p could further promote the effect of HADSCs-exosome on HUVECs. MiR-125a-3p from HADSCs-exosome inhibited the expression of PTEN in HUVECs. Knockdown of PTEN promoted the viability, migration, and angiogenesis of HUVECs and reversed the effect of miR-125a-3p knockdown on HUVECs. Finally, miR-125a-3p from HADSCs-exosome could promote wound healing and angiogenesis in mice by inhibiting PTEN in mice wound granulation tissues. MiR-125a-3p from the HADSCs-exosome promoted the wound healing and angiogenesis, and these effects were achieved through regulating PTEN. This study may provide a new thought for the treatment and prevention of tissue repair.

Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis.

It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and ß-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/ß-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.

Effect of six-stitch pancreaticojejunostomy on pancreatic fistula: A propensity score-matched comparative cohort study.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most common and severe complication after pancreaticoduodenectomy (PD). Despite the development of numerous anastomotic surgical techniques to minimize CR-POPF, more than 30% of patients who undergo PD develop CR-POPF. Herein, we propose a novel pancreaticojejunostomy (PJ) technique and evaluate its efficacy and safety compared to traditional PJ. METHODS: This retrospective study enrolled 164 consecutive patients who underwent PJ after PD between January 2012 and June 2017. Of them, 78 (47.6%) underwent traditional PJ and 86 (52.4%) underwent six-stitch PJ. The primary outcome was CR-POPF at 1-month follow-up defined according to the revised 2016 International Study Group on Pancreatic Fistula definition. To adjust for baseline differences and selection bias, patients were matched by propensity scores, which left 63 patients with traditional PJ and 63 with six-stitch PJ. RESULTS: Compared to patients who underwent traditional PJ (mean age 56.2 ± 9.4 years), patients who underwent six-stitch PJ (mean age 57.4 ± 11.4 years) had a lower CR-POPF rate. The risk of CR-POPF among patients who underwent six-stitch PJ was decreased by 81.7% after adjustment for age, sex, body mass index, and disease severity compared to patients who underwent traditional PJ. Additionally, the surgery time was reduced from 29 min for traditional PJ to 15 min for six-stitch PJ (P <0.001). Adverse effects such as abdominal fluid collection, abdominal bleeding, and wound infection were similar between two groups. CONCLUSION: Six-stitch PJ may be an effective and efficient PJ technique for patients who undergo PD surgery.

The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats

Abstract Objective To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment.

Aptamer-conjugated PEGylated quantum dots targeting epidermal growth factor receptor variant III for fluorescence imaging of glioma.

The extent of resection is a significant prognostic factor in glioma patients. However, the maximum safe resection level is difficult to determine due to the inherent infiltrative character of tumors. Recently, fluorescence-guided surgery has emerged as a new technique that allows safe resection of glioma. In this study, we constructed a new kind of quantum dot (QD)-labeled aptamer (QD-Apt) nanoprobe by conjugating aptamer 32 (A32) to the QDs surface, which can specially bind to the tumors. A32 is a single-stranded DNA capable of binding to the epidermal growth factor receptor variant III (EGFRvIII) specially distributed on the surface of glioma cells. To detect the expression of EGFRvIII in human brain tissues, 120 specimens, including 110 glioma tissues and 10 normal brain tissues, were examined by immunohistochemistry, and the results showed that the rate of positive expression of EGFRvIII in the glioma tissues was 41.82%, and 0.00% in normal brain tissues. Besides, the physiochemical properties of QD-Apt nanoparticles (NPs) were thoroughly characterized. Biocompatibility of the NPs was evaluated, and the results suggested that the QD-Apt was nontoxic in vivo and vitro. Furthermore, the use of the QD-Apt in labeling glioma cell lines and human brain glioma tissues, and target gliomas in situ was also investigated. We found that not only could QD-Apt specially bind to the U87-EGFRvIII glioma cells but also bind to human glioma tissues in vitro. Fluorescence imaging in vivo with orthotopic glioma model mice bearing U87-EGFRvIII showed that QD-Apt could penetrate the blood-brain barrier and then selectively accumulate in the tumors through binding to EGFRvIII, and consequently, generate a strong fluorescence, which contributed to the margins of gliomas that were visualized clearly, and thus, help the surgeons realize the maximum safe resection of glioma. In addition, QD-Apt can also be applied in preoperative diagnosis and postoperative examination of glioma. Therefore, these achievements facilitate the use of tumor-targeted fluorescence imaging in the diagnosis, surgical resection, and postoperative examination of glioma.

27 T ultra-high static magnetic field changes orientation and morphology of mitotic spindles in human cells.

Purified microtubules have been shown to align along the static magnetic field (SMF) in vitro because of their diamagnetic anisotropy. However, whether mitotic spindle in cells can be aligned by magnetic field has not been experimentally proved. In particular, the biological effects of SMF of above 20 T (Tesla) have never been reported. Here we found that in both CNE-2Z and RPE1 human cells spindle orients in 27 T SMF. The direction of spindle alignment depended on the extent to which chromosomes were aligned to form a planar metaphase plate. Our results show that the magnetic torque acts on both microtubules and chromosomes, and the preferred direction of spindle alignment relative to the field depends more on chromosome alignment than microtubules. In addition, spindle morphology was also perturbed by 27 T SMF. This is the first reported study that investigated the cellular responses to ultra-high magnetic field of above 20 T. Our study not only found that ultra-high magnetic field can change the orientation and morphology of mitotic spindles, but also provided a tool to probe the role of spindle orientation and perturbation in developmental and cancer biology.

Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway.

The study aimed to investigate the protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats (SHRs) through the Cys-C/Wnt signaling pathway. Thirty SHRs were randomly divided into cardiac hypertrophy, low- and high-dose tanshinone IIA groups. Ten Wistar-Kyoto rats were selected as control group. The systolic blood pressure (SBP), heart weight (HW), left ventricular weight (LVW) and body weight (BW) of all rats were recorded. HE staining and qRT-PCR were applied to observe the morphology of myocardial tissue and mRNA expressions of COL1A1 and COL3A1. ELISA and Western blotting were used to measure the serum asymmetric dimethylarginine (ADMA), nitric oxide (NO) and cardiac troponin I (cTnI) levels, and the expressions of the Cys-C/Wnt signaling pathway-related proteins, eNOS and Nox4. Compared with the cardiac hypertrophy group, the SBP, HW/BW, LVW/BW, swelling degree of myocardial cells, COL1A1 and COL3A1 mRNA expressions, serum cTnI and ADMA levels, and the Cys-C/Wnt signaling pathway-related proteins and Nox4 expressions in the low- and high-dose tanshinone IIA groups were decreased, but the endothelial NO synthase (eNOS), phosphorylated eNOS (Ser1177) and NO expressions were increased. No significant difference was found between the low- and high-dose tanshinone IIA groups. Our study indicated a protective effect of tanshinone IIA against cardiac hypertrophy in SHRs through inhibiting the Cys-C/Wnt signaling pathway.

KIAA0247 suppresses the proliferation, angiogenesis and promote apoptosis of human glioma through inactivation of the AKT and Stat3 signaling pathway.

Gliomas are the most common and aggressive type of primary adult brain tumors. Although KIAA0247 previously is a speculated target of the tumor suppressor gene, little is known about the association between KIAA0247 and glioma. In this study, we clearly demonstrate that KIAA0247 expression is decreased in glioma and was negatively correlated with the histologic grade. Overexpression of KIAA0247 in glioma cells inhibits proliferation, angiogenesis and promoted apoptosis of human glioma cells in vitro. In contrast, knockdown of KIAA0247 increases the proliferation, angiogenesis and decreases apoptosis of these cells. In a tumor xenograft model, overexpression of KIAA0247 suppresses tumor growth of glioma cells in vivo, while KIAA0247 knockdown promotes the tumor growth. Mechanistically, overexpression of KIAA0247 is able to inhibit phosphorylation of AKT and Stat3 in glioma cells, resulting in inactivation of the AKT and Stat3 signaling pathways, this ultimately decreases the expression of PCNA, CyclinD1, Bcl2 and VEGF. Collectively, these data indicate that KIAA0247 may work as a tumor suppressor gene in glioma and a promising therapeutic target for gliomas.

Role of Liquid-based Cytology and Cell Block in the Diagnosis of Endometrial Lesions.

BACKGROUND: Liquid-based cytology (LBC) offers an alternative method to biopsy in screening endometrial cancer. Cell block (CB), prepared by collecting residual cytological specimen, represents a novel method to supplement the diagnosis of endometrial cytology. This study aimed to compare the specimen adequacy and diagnostic accuracy of LBC and CB in the diagnosis of endometrial lesions. METHODS: A total of 198 women with high risks of endometrial carcinoma (EC) from May 2014 to April 2015 were enrolled in this study. The cytological specimens were collected by the endometrial sampler (SAP-1) followed by histopathologic evaluation of dilatation and curettage or biopsy guided by hysteroscopy. The residual cytological specimens were processed into paraffin-embedded CB after LBC preparation. Diagnostic accuracies of LBC and CB for detecting endometrial lesions were correlated with histological diagnoses. Chi-square test was used to compare the specimen adequacies of LBC and CB. RESULTS: The specimen inadequate rate of CB was significantly higher than that of LBC (22.2% versus 7.1%, P < 0.01). There were 144 cases with adequate specimens for LBC and CB preparation. Among them, 29 cases were atypical endometrial hyperplasia (11 cases) or carcinoma (18 cases) confirmed by histology evaluation. Taking atypical hyperplasia and carcinoma as positive, the diagnostic accuracy of CB was 95.1% while it was 93.8% in LBC. When combined LBC with CB, the diagnostic accuracy was improved to 95.8%, with a sensitivity of 89.7% and specificity of 97.4%. CONCLUSIONS: CB is a feasible and reproducible adjuvant method for screening endometrial lesions. A combination of CB and LBC can improve the diagnostic accuracy of endometrial lesions.

Area disparity in children's perceptions of access to tobacco and cigarette purchasing experiences in Taiwan.

BACKGROUND: Adolescents who perceive easy access to tobacco are more likely to acquire cigarettes and experience smoking. This study assesses area disparities in perceptions of access to tobacco and cigarette purchasing experiences among schoolchildren. METHODS: Data on children's tobacco-related variables were obtained from the Control of School-Aged Children Smoking Study Survey in Taiwan. A stratified random sample of 65 primary schools was included. Polytomous logistic regression analyzed factors associated with tobacco accessibility and purchasing experiences. RESULTS: More than half of the children reported that tobacco retailers often or always sold cigarettes to them. Rural and mountainous children were more likely to have access to cigarettes (adjusted odds ratio [AOR] = 2.01 and 3.01, respectively) and have cigarette purchasing experiences (AOR = 3.06 and 13.76, respectively). Cigarette purchasing from retailers (AOR = 1.84) was significantly associated with children's perceptions of access to tobacco. The factors associated with cigarette purchasing experiences were families smoking (AOR = 8.90), peers smoking (AOR = 2.22), frequent exposure to entertainer smoking on TV and in films (AOR = 2.15), and perceived access to tobacco (AOR = 1.51). CONCLUSIONS: The health department should strictly enforce laws regarding retailers selling tobacco to underage, particularly in remote areas. Schools can reinforce tobacco-use prevention messages.

Analysis of influential factors associated with the smoking behavior of aboriginal schoolchildren in remote Taiwanese mountainous areas.

BACKGROUND: A disparity in smoking behavior exists between the general and minority populations residing in Taiwan's mountainous areas. This study analyzed individual and environmental factors associated with children's smoking behavior in these areas of Taiwan. METHODS: In this school-based study, data on smoking behavior and related factors for mountain-dwelling students were obtained from the 2008 and 2009 Control of School-aged Children Smoking Study surveys. A representative sample (N = 1239) from 26 primary schools was included. The association among 3 groups (never-, former-, and current-smokers) and the potential variables were simultaneously examined using unordered polytomous logistic regression analysis. RESULTS: Between 13% and 34% of ever-smokers reported that their first smoking experience was in third grade. More than 70% were found to have bought cigarettes and 87% reported that the tobacco retailers had sold them cigarettes. The significant factors for current-smokers were predisposing factors, ie, attitude toward smoking (adjusted odds ratio [AOR] = 1.21); reinforcing factors, ie, family smoked in front of me (AOR = 2.44), friends smoked in front of me (AOR = 16.24), and school staff smoked in front of me (AOR = 2.98); and enabling factors, ie, cigarette availability and accessibility (AOR = 2.16 and 2.42, respectively). A student's perceived punishment for smoking at school had a positive significant effect on the risk of being former-smokers (AOR = 1.57). CONCLUSION: The findings provide a basis for school and community to design and implement effective anti-smoking programs for remote mountain-based students to further reduce youth smoking.

Household secondhand smoke exposure of elementary schoolchildren in Southern Taiwan and factors associated with their confidence in avoiding exposure: a cross-sectional study.

BACKGROUND: Exposure to household Secondhand Smoke (SHS) poses a major health threat to children after an indoor smoking ban was imposed in Taiwan. This study aimed to assess the household SHS exposure in elementary school children in southern Taiwan and the factors associated with their avoidance of SHS exposure before and after the implementation of Taiwan's new Tobacco Hazards Prevention Act in 2009. METHODS: In this cross-sectional school-based study, data on household SHS exposure, avoidance of SHS and related variables was obtained from the 2008 and 2009 Control of School-aged Children Smoking Study Survey. A random sample of 52 elementary schools was included. A total of 4450 3-6 graders (aged 8-13) completed the questionnaire. Regression models analyzed factors of children's self-confidence to avoid household SHS exposure. RESULTS: Over 50% of children were found to have lived with a family member who smoked in front of them after the new law enacted, and 35% of them were exposed to household SHS more than 4 days a week. Having a positive attitude toward smoking (ß = -0.05 to -0.06) and high household SHS exposure (ß = -0.34 to -0.47) were significantly associated with a lower avoidance of SHS exposure. Comparing to girls, boys had lower scores in their knowledge of tobacco hazards; and this factor was significantly related to their SHS avoidance (ß = 0.13-0.14). CONCLUSIONS: The intervention program should enhance school children do actively avoid exposure to SHS in home settings, and more importantly, provide tobacco hazard knowledge to male students to avoid exposure to household SHS for themselves. The results also provide further evidence that Tobacco Hazards Prevention Act should perhaps be extended to the family environment in order to protect children from the hazards of household SHS exposure.

Initial Progression-Free Survival after Non-First Line TKIs Therapy Potentially Guides Immediate Treatment after Its Failure in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: The standard therapy after failure of the initial non-first line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in advanced non-small cell lung cancer (NSCLC) has not yet been established. The aim of the current study was to identify whether the 2(nd) TKI treatment or chemotherapy (paclitaxel-containing or non-paclitaxel regimen) is the appropriate treatment for patients with NSCLC based on the efficacy of the initial TKIs. METHODS: Seventy-two advanced NSCLC patients who had accepted 2(nd) TKIs or chemotherapy immediately after failure of the initial TKIs in non-first line setting from May 1, 2004 to January 31, 2010 at the Sun Yat-sen University Cancer Center were enrolled. The primary endpoint [2(nd) progression-free survival (PFS)] and the second endpoint [overall survival (OS)] were compared among the 2(nd) TKI and chemotherapy groups as well as their subgroups. RESULTS: (1) Twenty-one patients were treated with 2(nd) TKIs, and 51 patients were administered chemotherapy after failure of the initial non-first line TKI treatment. There was nonsignificant difference in the responses (P=0.900) [2(nd) PFS (P=0.833) and OS (P=0.369)] between the 2(nd) TKI and chemotherapy groups. (2) In the 2(nd) TKI group, 9 patients exhibited PFS≥7 months. The initial TKI treatment group exhibited a longer 2(nd) PFS than the other 12 patients with an initial PFS<7 months (7 months vs. 2 months, P=0.019). However, these groups had nonsignificantly different OS (P=0.369). (3) In the chemotherapy group, patients with PFS<5 months exhibited longer 2(nd) PFS than those with PFS ≥ 5 months in the initial TKI treatment (3 months vs. 2 months, P=0.039). (4) In the chemotherapy group, patients treated with paclitaxel-containing regimen showed longer 2(nd) PFS than those treated with non-paclitaxel regimen (5 months vs. 2.3 months, P=0.043). CONCLUSIONS: Patients with PFS≥7 months or <5 months under the initial TKI treatment potentially benefit from the 2(nd) TKI treatment or chemotherapy immediately after failure of the non-first line TKIs. The paclitaxel-containing regimen may improve the 2(nd) PFS. However, more patient samples are urgently needed to validate these findings.

Short-term outcomes of cetuximab combined with standard chemotherapy as first line setting for Chinese patients with non-small cell lung cancer: a report of 12 cases.

Cetuximab combined with chemotherapy has been used to treat Non-small cell lung cancer (NSCLC) in recent years, however, the data from China was rare. This study was to summarize our experiences in treating NSCLC patients with cetuximab in the first line setting. From October 1st 2006 to Jun 30th 2010, twelve NSCLC patients were treated with cetuximab combined standard chemotherapy as first line setting in Sun Yat-sen University Cancer Center entered the study and the short-term efficacy and safety were analyzed. A total of 132 cycles of cetuximab treatment, with a median of nine cycles in the whole group were administered. The ORR was 41.7% (5/12), DCR was 83.3% (10/12), median TTP was 5.5 months (2-23), and median OS was 9 months (2-48) in the whole group. There were 75% (9/12) patients occurred acne-like rash within first 3 weeks, their ORR was 55.6% (5/9), DCR was 100% (9/9), however, ORR and DCR in patients who didn't occurred acne-like rash within first 3 weeks were 0 and 33.3% (1/3), the difference ORR between two group was insignificant (P = 0.091), however, DCR was significant different (P = 0.007). There no treatment-associated death and no cetuximab-associated discontinuation. The incidence of acne-like rash was 83.3% (10/12) and 75% (9/12) occurred within first 3 weeks, there were eight patients suffered side effects associated with chemotherapy. So we can draw a conclusion that the short-term outcome of cetuximab application in first line setting for patients with NSCLC were promising since the higher ORR and DCR, especially those occurred acne-like rash within the first 3 weeks, and the addition of cetuximab in this population was safe.

Second-hand smoke exposure and the factors associated with avoidance behavior among the mothers of pre-school children: a school-based cross-sectional study.

BACKGROUND: Second-hand Smoke (SHS) exposure is a significant public health problem that may be responsible for serious health hazards for child. This study aimed to examine the exposure status of SHS and the factors associated with SHS avoidance behavior among the mothers of pre-school children. METHODS: A cross-sectional study was used to obtain a sample of the mothers of pre-school children (n = 1,020) in 30 registered kindergartens in eastern Taiwan. Overall, 919 (a response rate of 90%) completed the questionnaires. Regression models were used to identify factors with respect to the avoidance behavior of SHS. RESULTS: The prevalence of exposure to SHS was 70% and 50% for the mothers and their children, respectively. After adjusting for other variables, mothers who were current smokers (ß = -0.260, p < 0.001), had spouses who smoked (ß = -0.060, p < 0.05), SHS exposure (ß = -0.138, p < 0.001), and/or children with exposure to SHS (ß = -0.084, p < 0.05) were found to be less likely to avoid SHS, whereas mothers with a high knowledge score about SHS (ß = 0.082, p < 0.01), positive attitudes (ß = 0.274, p < 0.001) and a high self-efficacy level in regard to the avoidance of SHS (ß = 0.397, p < 0.001) were observed to be more likely to avoid SHS. Regression analyses confirmed that the significantly factors associated with the avoidance behavior of SHS were self-efficacy, being a current smoker, and the attitude toward the avoidance of SHS to be that of 55.5% of the total variance explained (p < 0.001). CONCLUSIONS: The high prevalence rate of exposure to SHS for mothers and their children suggests that a well-designed future intervention program should be implemented in regard to pre-school children's mothers in order to prevent these mothers and their children from SHS exposure hazards, more particularly, to strengthen the knowledge base, to enhance self-efficacy and to foster a more positive attitude toward the avoidance of SHS in the mothers.

Heparinized chitosan/poly(γ-glutamic acid) nanoparticles for multi-functional delivery of fibroblast growth factor and heparin.

To improve blood supply following ischemic injury, angiogenic factors such as fibroblast growth factor (bFGF) that stimulate new blood vessel formation have been used for therapeutic angiogenesis in ischemic tissues. In this study, heparin-functionalized chitosan (CS)/poly(γ-glutamic acid) (γ-PGA) nanoparticles (HP-CS/γ-PGA nanoparticles) were prepared for multi-functional delivery of basic fibroblast growth factor (bFGF) and heparin. The mean particle sizes and bFGF loading efficiency increased with the increase of functionalized heparin contents. The HP-CS/γ-PGA nanoparticles were pH-sensitive that could sustain bFGF release at pH 񥌈 6.7 (simulate the pH of ischemia tissue) and were rapidly disintegrated at pH 7.4 (simulate the pH of repaired tissue). Sustained release of bFGF from the nanoparticles enhanced the proliferation of human foreskin fibroblast cells (HFF) and angiogenic tube formation by human umbilical vein endothelial cells (HUVEC), suggesting the retaining of bFGF mitogenic activity. Heparin, a traditionally used anticoagulant, could release from the disintegrated nanoparticles to maintain the anti-factor Xa activity in blood plasma, after increasing the pH value from 6.6 to 7.4. The nanocarriers for multi-functional delivery of bFGF and heparin developed in this study may be a potential therapeutic method for enhancing ischemic tissue regeneration and preventing blood vessel rethrombosis.