OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

Objective: To analyze the correlation between integrin β₁, focal adhesion kinase (FAK), extracellular signal-regulated kinase 1/2 (ERK1/2) of hypertrophic scar (HS) and post injury time in burn patients in scar remodeling stage. Methods: Thirty-four patients with 34 HS specimens admitted to Department of Burns and Plastic Surgery of Chengdu No.2 Hospital and Institute of Burn Research of the First Affiliated Hospital of Army Medical University (originally the Third Military Medical University) from May 2013 to April 2016 were recruited by convenient sampling method, and normal skin specimens were obtained from donor sites of another 6 patients from the above-mentioned departments who had scar resection and skin grafting for this cross-sectional and observational study. Vancouver Scar Scale (VSS) was used to assess the height, vascularity, pigmentation, and pliability of scars. Diasonograph was used to assess scar thickness. Immunohistochemical method was used to observe the expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar and normal skin. Correlations between the post injury time and the scar thickness, the post injury time and the expressions of integrin β₁, FAK, and ERK1/2 in epidermis of scar, the post injury time and the expressions of integrin β₁, FAK, and ERK1/2 in dermis of scar, the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar were analyzed by Pearson correlation analysis. Locally estimated scatterplot smoothing curve fitting line was used to demonstrate the non-linear regression relationship between the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar, the scar thickness and the post injury time. Results: (1) The total VSS score of scars of patients was (8.3±2.3) points, with height scored (2.2±0.7) points, vascularity scored (2.0±0.8) points, pigmentation scored (2.3±0.7) points, and pliability scored (1.9±0.7) points. The thickness of scar was (2.8±1.1) mm. (2) The expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar were more than those in normal skin. (3) There was significantly positive correlation between the scar thickness and the post injury time (r=0.39, P<0.05). There was significantly positive correlation between the expression of integrin β₁ in epidermis of scar and the post injury time (r=0.33, P<0.05). There were no significantly correlations between the expressions of FAK and ERK1/2 in epidermis of scar and the post injury time (r=-0.03, -0.04, P>0.05). There was significantly negative correlation between the expression of FAK in dermis of scar and the post injury time (r=-0.34, P<0.05). There were no significantly correlations between the expressions of integrin β₁ and ERK1/2 in dermis of scar and the post injury time (r=0.07, -0.23, P>0.05). There were significantly positive correlation between the expressions of integrin β₁, FAK, and ERK1/2 in dermis and those in epidermis of scar (r=0.70, 0.60, 0.64, P<0.01). (4) The expressions of integrin β₁, FAK, and ERK1/2 in dermis and epidermis of scar were changed from downtrend in 1 to 2 months post injury to uptrend in 2 to 3 months post injury, which reached the peak around 3 to 4 months post injury. Hereafter the expressions of mechanical signaling molecules in epidermis of scar were gradually declined, while the expressions of mechanical signaling molecules in dermis of scar were at a quite high level within half a year post injury. Scar thickness was steadily increased after 1 month post injury. Conclusions In scar remodeling stage of burn patients, the HS thickness increases continuously along with the increasing post injury time in the early stage of scar formation. The vulnerability of integrin β₁, FAK, and ERK1/2 of HS to external mechanical stimuli increases gradually within 4 months post injury.

The cochlea of children with congenital sensorineural hearing loss with normal inner ear structure was measured and analyzed by high-resolution temporal bone CT(HRCT) imaging technique,its application value before cochlear implantation was evaluated and the appropriate electrode was selected.We collected temporal bone HRCT images of 120 patients with congenital sensorineural hearing loss,according to gender divided into two groups,including 60 males and 60 females.We used the PACS software to measure the distance A(the largest distance from the round window to the lateral wall) and the distance H(height of the cochlea) and calculate the cochlear duct length. Reproducibility of these data were evaluated and the results between the different groups were compared.Measurement of parameter values between the intraobserver and interobserver showed great reproducibility. In the male children group,the measured values are shown as distance A［(8.55±0.31)mm］,distance H［(4.57±0.28)mm］and the cochlear duct length(CDL)［(27.59±1.23)mm］; and in the female children group, the measured values are shown as distance A［(8.45±0.32)mm］,distance H［(4.42±0.34)mm］and the cochlear duct length(CDL)［(27.20±1.17)mm.The A,H,and CDL of the male cochlea were greater than those of the female, the difference was statistically significant(<0.05).Measuring the distance A and distance H of the cochlea and calculating the cochlear duct length CDL can be used to select a suitable length of electrode or to customize a personalized electrode. This is a simple and effective assessment method before cochlear implantation..

OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.
Altitude ; Multiple Organ Failure/*diagnosis ; Prognosis ; ROC Curve ; Regression Analysis ; Respiratory Distress Syndrome, Adult/*diagnosis ; Severity of Illness Index

Background: Despite evidence supporting the safety of breast implants, some women associate their implants with adverse health effects and have called this syndrome “breast implant illness.” We sought to characterize breast implant illness symptoms and to report how implant removal affects their symptoms. Methods: An anonymous 20 question survey was administered to the Facebook group: “UTAH Breast Implant Illness” to characterize the symptoms these women attributed to their breast implants. Several questions allowed us to evaluate how implant removal affected women’s symptoms. Results: Of the 182 respondents, 97% report that implants negatively affect their health and 95% identify these symptoms with breast implant illness. Ninety-six percent of respondents had implants placed for cosmetic reasons and 51% had silicone implants. The most common symptoms associated with breast implant illness are brain fog (95%), fatigue (92%), joint pain (80%), and hair loss (74%). Sixty percent of respondents learned about breast implant illness from family/friends and/or social media platforms (56%), 40% of respondents had their implants removed, and 97% report relief of their symptoms post-removal (23% complete, 74% partial). Following explantation, there was a significant improvement in all but one reported symptom. An association was found between the number of symptoms reported prior to explantation and the number of symptoms resolving following explantation. Conclusions Breast implant illness is a syndrome characterized by fatigue, decreased focus, hair loss, and joint pain after the placement of breast implants. Nearly all patients report improvement of symptoms after implant removal. Significant efforts should be made to better understand breast implant illness and its etiology.

Background: Despite evidence supporting the safety of breast implants, some women associate their implants with adverse health effects and have called this syndrome “breast implant illness.” We sought to characterize breast implant illness symptoms and to report how implant removal affects their symptoms. Methods: An anonymous 20 question survey was administered to the Facebook group: “UTAH Breast Implant Illness” to characterize the symptoms these women attributed to their breast implants. Several questions allowed us to evaluate how implant removal affected women’s symptoms. Results: Of the 182 respondents, 97% report that implants negatively affect their health and 95% identify these symptoms with breast implant illness. Ninety-six percent of respondents had implants placed for cosmetic reasons and 51% had silicone implants. The most common symptoms associated with breast implant illness are brain fog (95%), fatigue (92%), joint pain (80%), and hair loss (74%). Sixty percent of respondents learned about breast implant illness from family/friends and/or social media platforms (56%), 40% of respondents had their implants removed, and 97% report relief of their symptoms post-removal (23% complete, 74% partial). Following explantation, there was a significant improvement in all but one reported symptom. An association was found between the number of symptoms reported prior to explantation and the number of symptoms resolving following explantation. Conclusions Breast implant illness is a syndrome characterized by fatigue, decreased focus, hair loss, and joint pain after the placement of breast implants. Nearly all patients report improvement of symptoms after implant removal. Significant efforts should be made to better understand breast implant illness and its etiology.

Objective To investigate the clinical characteristics and risk factors of intra- and post-operative reperfusion injury following surgical evacuation of epidural hematoma. Methods Clinical and radiographic data of 206 patients with cerebral herniation presented with an epidural hematoma and underwent surgical evacuation in our hospital from June 2009 to June 2015, were retrospectively analyzed; risk factors of intra- and post-operative reperfusion injury were analyzed by multi-factor and non-conditional Logistic regression analyses. Results A total of 12 patients with acute epidural hematoma and concurrent cerebral herniation developed reperfusion injury after hematoma evacuation; 7 patients (58.3%) were within 15-30 min after surgical evacuation intraoperatively and 5 patients (41.7%) were at an early stage within 6 h after operation. Local vascular cerebral edema, effusion, or even spot and patchy hemorrhage in the compressed cerebral parenchyma underneath the epidural hematoma were depicted by craniocerebral CT/MR imaging examination and further CT perfusion examination confirmed the local hyperperfusion-induced lesions. These 12 patients had an unsatisfactory clinical outcome with a high ratio of bad prognosis (58.3%, 7/12). Regression analyses indicated that the described surgical complication was significantly associated with duration of preoperative cerebral herniation (≥120 min, odds ratio [OR]=61.617, P=0.001), hematoma thickness (≥40 mm, OR=10.051, P=0.018). Conclusions Cerebral herniation longer than 120 min and hematoma thickness greater than 40 mm are high-risk factors associated with intra- and post-operative reperfusion injury. Controlled decompressive surgical strategy is helpful for a good recovery of cerebrovascular autoregulation function and thereby reduces the occurrence of reperfusion injury.

Objective: To investigate the association between three single nucleotide polymorphism (SNP) genes DRD2 (rs1800497, rs6275, and rs1799978) and the dosage used on methadone maintenance treatment (MMT). Methods: From the methadone maintenance treatment centers, 257 MMT patients were recruited to participate in a case-control study and divided into two groups-control groups under low dosage (n=89) and case (n=168) group with high dosage. Quanto software was used to estimate the sample size as 180. Information related to social-demographic status, history on drug use and medication were collected. And DRD2 SNPs were genotyped to explore the relationship between polymorphism of DRD2 gene and the dosage of methadone maintenance treatment. Results: Distributions of DRD2 rs6275 between different groups were significantly different. Patients carrying TC genotype needed lower dose of methadone when compared to the patients that carrying CC genotype counterparts (OR=0.338, 95% CI: 0.115-0.986). Patients that carrying C allele at rs6275 needed lower methadone dose than those that carrying genotype TT (OR=0.352, 95% CI: 0.127-0.975). Distributions of genotypes, alles in the other two SNPs (rs1800497, rs1799978) were not significantly different between groups under different dosages. Conclusion: DRD2 rs6275 was associated with dosage of methadone used for the MMT patients. However, no significant associations were found between rs1800497, rs1799978 and the dosage of methadone.
Alleles ; Case-Control Studies ; Drug Dosage Calculations ; Genotype ; Humans ; Methadone/therapeutic use* ; Opiate Substitution Treatment ; Opioid-Related Disorders/rehabilitation* ; Polymorphism, Single Nucleotide/genetics* ; Receptors, Dopamine D2/genetics*

Objective: To explore the reasons and factors associated with new psychoactive substances abuse among patients with access to methadone maintenance treatment (MMT). Methods: A well-developed questionnaire and urine tests were used to collect information about demographic characteristics, condition of MMT and drug abuse, family and social support of MMT clients. A 1∶1 matched case-control study was conducted, and conditional logistic regression model was used to identify factors associated with new psychoactive substances abuse. Results: A total of 212 (106 pairs) clients receiving MMT were recruited, and most of them were males (78.3%, 166/212), married or cohabitant (48.6%, 103/212) and unemployed (63.2%, 134/212). The average age of the clients was (45.1±7.2) years. The main types of abused new psychoactive substances were benzodiazepine (62.3%, 66/106) and methamphetamine (39.6%, 42/106). The proportion of abusing multi new psychoactive substances was 8.5% (9/106). Results from multivariate conditional logistic regression analysis indicated that using opioid drug during the past 6 months of MMT treatment might increase the risk of abusing new psychoactive substances (OR=3.25, 95%CI: 1.35-7.79), benzodiazepine (OR=3.25, 95%CI: 1.11- 9.47) and methamphetamine (OR=13.31, 95%CI: 1.12-158.01). Moreover, MMT for more than9 years reduced the risk of abuse of new psychoactive substances (OR=0.03, 95%CI: 0.01-0.21), benzodiazepine (OR=0.02, 95%CI: 0.00-0.36) and methamphetamine (OR=0.02, 95%CI: 0.00-0.69). Conclusion: Less new psychoactive substances abuse might be associated with longer duration of MMT treatment. And inappropriate support from family and friends might increase the risk of abusing new psychoactive substances in MMT clients, especially in clients who used opioid.
Adult ; Case-Control Studies ; China/epidemiology* ; Drug Users/statistics & numerical data* ; Humans ; Logistic Models ; Male ; Methadone/therapeutic use* ; Methamphetamine ; Middle Aged ; Opiate Substitution Treatment ; Prevalence ; Psychotropic Drugs/adverse effects* ; Substance Abuse Detection/statistics & numerical data* ; Substance Abuse Treatment Centers ; Substance-Related Disorders/epidemiology* ; Surveys and Questionnaires

The process of globalization increases the risk of global transmission of infectious diseases, resulting in pressure for country's prevention and control of imported infectious disease. Based on the risk assessment of disease importation and local transmission, a strategy that conducting importation prevention and routine prevention and control before the importation of disease and taking emergency control measures after the importation of disease was developed. In addition, it is important to take part in global infectious disease response action, aid the countries with outbreak or epidemic to actively decrease the risk of disease importation.
Communicable Diseases ; Communicable Diseases, Imported/transmission* ; Disease Outbreaks/prevention & control* ; Epidemics ; Global Health ; Humans ; Risk Assessment ; Travel