Hollow copper sulfide nanoparticles carrying ISRIB for the sensitized photothermal therapy of breast cancer and brain metastases through inhibiting stress granule formation and reprogramming tumor-associated macrophages

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Deafness Gene Screening and AABR in Children Hearing Loss Diagnose / 听力学及言语疾病杂志

Objective The aim of this study was to find out the carrying rate and the type of mutation of children deafness gene and discuss the significance of combined screening of deafness gene and hearing screening.Methods From October 2015 to December 2016,a total of 505 children from primary screening institutions were done with AABR hearing re-screening and deafness gene through blood filter paper by heel for gene sequencing at the hearing screening clinic of Hefei Maternal and Child Health Hospital.The 9 mutation sites of deafness genes included GJB2 (235delC,299delAT,176del16,35delG),GJB3 (538C＞T),SLC26A4 (IVS7-2A＞G,2168A＞G) and mitochondrial 12SrRNA (1555A＞G,1494C＞T).Results There were 69 children with deafness susceptibility genes in 505 cases and its overall carrying rate was 13.7％.There were 56 cases (81.16％)with GJB2 gene mutations,10 cases (14.49％) with SLC26A4 gene mutations,and 3 patients (4.35％) with mitochondrial 12SrRNA gene mutations.GJB3 gene mutations wer not detected.There were 376 who failed AABR rescreening out of 505.The total failure rate for AABR rescreening was 74.46％.Thirty-seven cases were examined with ABR out of 69 cases with deafness gene abnormal.32 cases (86.49％) had different degrees of hearing impairment.Conclusion GJB2 gene mutation was the highest carrying rate of deafness genes in this region,followed by SLC26A4 gene,less mitochondrial 12SrRNA gene mutations while GJB3 gene mutations was not detected.Hereditary deafness gene screening was a valid supplement for physical screening,the combination of both methods was helpful for early detection and intervention of deaf children.

Relationship between depressive symptoms and social capital,social networks among female migrant adolescents in Hefei / 中华疾病控制杂志

Objective Learn about prevalence of depressive symptoms and to determine the relationship of depressive symptoms with social capital and social networks among migrant female adolescents.Methods A cross-sectional survey was conducted among 329 single females selected by convenience sampling who were aged from 16 to 28 years old,having worked for from one month to ten years.Center for Epidemiologic Studies Depression Scale(CES-D) was used to evaluate the status of depressive symptoms that were sentenced by total score ≥20.Self-compiled items were applied to assess social capital with six aspects involving organizational characteristics,exclusion,etc.and social networks included size and density with score ranging from 1 to 15 and from 0 to 1 respectively.Results The prevalence of depressive symptom was 52.9% in participants.Working in restaurants(OR=0.554),being younger(OR=0.506),high scores of solidarity,trust and cooperation of neighborhood(OR=0.964,0.758) were associated with low risk of depressive symptoms.Conclusions Female migrant adolescents from rural to urban should be paid more attention to in depression prevention.Improving solidarity,trust and cooperation in neighborhood in city could probably decrease risk of their depressive symptoms.