Objective To analyze the detrimental effects of exposure to environmental noise alone and combined with carbon monoxide(CO)on spermatogenesis in male rats,investigate the underlying mechanisms involved in such damage,and evaluate the protective role of pterostilbene(PTE)against these adverse effects.Methods Sixty male SD rats(6～8 weeks old,weighing 200±10 g)were randomly divided normal control group(standard housing),sham-exposure control group(restraint stress only),noise exposure(85 dB),CO exposure(460 mg/m3),combined exposure(simultaneous exposure),and PTE intervention(80 mg/kg pretreatment),with 10 animals in each group.The rats were exposed daily for 2 h via a nose-only inhalation exposure system within a multifactorial environmental simulation chamber for 60 consecutive days.Sperm count and viability were measured after exposure.Histopathological changes of testicular tissues were observed with HE staining.qRT-PCR was used to measure stage-specific mRNA levels in germ cells.Serum sex hormone levels and adenosine triphosphate(ATP)concentrations in testes and sperm were detected.Transmission electron microscopy(TEM)was applied to observe the ultrastructural damage in the spermatocytes.Additionally,transcriptome sequencing was performed on testicular tissue,followed by bioinformatics analysis.Results Compared with the negative control group,the combined exposure group exhibited significant reductions in sperm viability and count(P<0.05),and developmental arrest of immature germ cells in the testicular tissue,with obviously less spermatogonia,spermatocytes,and round/elongated spermatids(P<0.01).Additionally,significantly reduced levels of reproductive-related hormones,such as gonadotropin-releasing hormone,follicle-stimulating hormone,luteinizing hormone and testosterone,and ATP levels in testes and sperm were observed in the mice after combined exposure(P<0.01),accompanied by mitochondrial rupture and cristae disruption in spermatocytes.Conversely,the PTE intervention group showed marked alleviation of these impairments,with parameters recovering almost to normal levels.Transcriptome sequencing identified biological processes related to reproductive development and ATP-dependent pathways as potential contributors to testicular injury induced by noise and CO exposure,with key genes including Nppa,Adm,Gnrh1,Ptafr,Atp13a5,Atp8b1,and LOC102555469.Conclusion Noise and CO exposure induce spermatogenic damage in rats,which may be related with energy metabolism and hormonal regulation,while PTE demonstrates significant protective effects against such reproductive impairments.

Objective: A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs). Methods: A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software. Results: No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the “any abuse” and “no abuse” groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679). Conclusion Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

HER2 gene is expressed in 20%-30% of breast cancer patients, and HER2 expression provides a new direction for treatment. However, breast cancer with positive HER2 still has a poor prognosis and is prone to recurrence and metastasis. Trastuzumab is a classic basic drug for anti-HER2 therapy. However, the problem of primary and acquired drug resistance of trastuzumab has attracted people's attention. Studies have found that the occurrence of insensitive and drug resistance mechanism is related to PD-L1 up-regulation on tumor cell surface. Therefore, a large number of studies on PD-1/PD-L1 inhibitor combined with trastuzumab were carried out to improve its sensitivity and drug resistance. This article reviews the preclinical and clinical studies on PD-1/PD-L1 inhibitors in breast cancer with positive HER2.

Objective To investigate the clinical outcomes of patients with locally advanced uterine cervical cancer (UCC) treated by 3-dimensional high dose rate-intracavitary brachytherapy (3D HDR-ICBT) combined with complementary applicator-guided external beam radiotherapy (EBRT).Methods A total of 120 patients pathologically diagnosed with locally advanced UCC (tumors with a maximum diameter≥6 cm or ≥5 cm complicated with eccentric tumor growth) treated with concurrent chemoradiotherapy (CCRT) from June 2010 to June 2015 were recruited.Five fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were performed.The prescribed dose for HR-CTV and IR-CTV was 7 Gy (D9o) and 5-6 Gy (D90).The rectum,sigmoid colon,bladder and adjacent small intestine were delineated as the organs at risk.Intensity-modulated radiation therapy (IMRT) was used for EBRT (45 Gy/ 25f) combined with cisplatin-based chemotherapy every three weeks (75 mg/m2).Results The median follow-up time was 46 months (14-96 months).The 5-year local control rate (LCR),disease-free survival (DFS),and overall survival (OS) were 92.8％,76.6％ and 81.0％,respectively.The incidence rate of grade Ⅰ-Ⅱ genitourinary and gastrointestinal acute toxicities were 57.8％ and 14.6％,whereas 8.1％ and 2.9％ for grade Ⅲ toxicities.The incidence rate of later grade Ⅰ-Ⅱ genitourinary and gastrointestinal toxicities were 8.4％ and 5.3％,and 0.97％ and 1.3％ for grade Ⅲ late toxicities.Conclusions The combination of HDR-ICBT with an applicator-guided IMRT (ICBT+IMRT) yields low incidence of severe adverse events,relatively high LC and OS rate for locally advanced UCC.It is an efficacious comprehensive treatment of locally advanced bulky UCC.

With population aging,the number of elderly subjects with frailty is increasing,and frailty can lead to adverse clinical outcomes.Early screening,early diagnosis and early prevention and treatment of frailty have important clinical significance.Due to increasing demand for early screening,early diagnosis and prognosis assessment,preliminary screening for frailty based on characteristic changes in specific proteomics may be a promising diagnostic strategy.At present,most research mainly focuses on skeletal muscle proteomics,inflammatory proteomics and vascular system proteomics.This review will summarize and analyze recent proteomic studies on protein profiles of frailty and non-frailty subjects.

Objective To investigate the role of high mobility group protein2(HMGA2)and E-Cadherin in the development of prostate cancer(PCa). Methods A total of 60 paraffln-embedded specimens of PCa were collected from patients who underwent operation in Dalian Central Hospital from 2008 to 2016.The expression lev-els of HMGA2 and E-Cadherin in the specimens were examined by immunohistochemical staining.The correlations between the expression of HMGA2 and E-Cadherin and clinical features such as age,Gleason score,invasion,me-tastasis and TNM stage were studied. Results The expression levels of HMGA2 in PCas were significantly higher than that in controls(χ2=51.818,P<0.01),but the positive expression levels of E-Cadherin in PCas were lower than that in controls(χ2=53.494,P<0.01).The positive expression of HMGA2 and the loss of E-Cadherin were confirmed in PCa accompanied by metastasis,seminal invasion,Gleason score>7 and stageⅢ~Ⅳ(P<0.05). Overexpression of HMGA2 was associated with down-regulation of E-cadherin(Spearman′s r=-0.569,P<0.01). Conclusions Up-regulation of HMGA2 and down-regulation of E-Cadherin are cooperatively correlated with the invasion and metastasis in PCa.