Objective In this study ,we investigated the apoptosis of hair cell in the cochlea of age -related hearing loss(AHL) generated by ENU mutagenesis ,and to study a pan caspase inhibitor (z-VAD -FMK) which is to protect the cochlea hair cells from hearing loss induced by age-related hearing loss(AHL) .Methods Through z-VAD-FMK intraperitoneal injection and round window membrane (RWM) drug were delivered into the Cdh23 nmf308 nmf/nmf mice 5(postnatal days 2 -32) inner ear .ResuIts The results showed that the nmf308 mice with progressive hair cell loss along a base to apex gradient with age-related hearing loss .The cochlear OHCs reduced from 5% ~10% at 1 month to 100% at 3 month in the basal region .Substantial amounts of TUNEL -positive OHCs nuclei appeared at 1 month age ,and activated caspase-3 labeling demonstrated that most OHCs appeared at 2 months age .These suggested that DNA single strand break was attributed primarily to apoptosis of cochlear le_sions ,whereas in the later stage of lesion ,the expansion led to activation of caspase-3 activity reduced with further progression of nuclear condensation in age-related hearing loss .ConcIusion The addition of a pan caspase inhibitor (z -VAD -FMK ) significantly protected the cochlea against the hair cell loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD-FMK appeared to play a prominent role in age-related hearing loss media_ted hair cell death loss induced by apoptosis .Our study showed that aspase inhibitor ,Z-VAD -FMK appeared to play a prominent role in age-related hearing loss mediated hair cell death .

Objective To explore the dynamic change and clinical signiticance of plasma D-damer level in patients with cerebral hemorrhage and acute craniocerebral injury.Methods 50 patients with cerebral hemorrhage and 40 patients with acute craniocerebral injury were selected,The enzyme-linked immunosorbent assay (ELISA) was used to measure plasma D-dimer level in two groups of patients after onset,and the results were compared with 40 healthy controls.Results The levels of plasma D-dimer in the patients with cerebral hemorrhage were 1.59mg/L,2.10mg/L,1.03 mg/L,0.82mg/L at 3 h,6h,12h,2d after onset,which in the patients with acute craniocerebral injury were 1.61mg/L,2.02mg/L,1.01mg/L and 0.67mg/L,respectively.And the plasma D-dimer levels were 0.50mg/L,0.49mg/L,0.47mg/L,0.48mg/L in the control group at 3h,6h,12h and 2d after onset.The levels of plasma D-dimer in the patients with acute craniocerebral injury were significantly higher than those in the control group,and the differences were statistically significant (t =9.35,12.17,4.03,3.05,all P ＜ O.05).At 7d after onset,the D-dimer levels in the cerebral hemorrhage group and acute craniocerebral injury group were 0.53mg/L,0.55mg/L,respectively,which of the control group was 0.47mg/L,there was no statistically significant difference among the three groups(P ＞ 0.05).Conclusion Cerebral hemorrhage patients and acute craniocerebral injury patients have high coagulation and fibrinolytic activity in brief increase trend,dynamic observation of plasma D-dimer level in patients with cerebral hemorrhage and acute craniocerebral injury is helpful to determine courses,condition and evaluate prognosis.

With the continuous development and maturity of anti-tumor immunotherapy technology,im-mune checkpoint inhibitors as one of the main methods of immunotherapy were increasingly widely used in clinical tumor cases,bringing new hope for many advanced cancer patients with poor response to tradi-tional treatment,but at the same time,reported on adverse reactions of various organs related to this were also increasing,and the immune damage caused by them was harmful to patients,especially immune checkpoint inhibitor-associated pneumonia,immune checkpoint inhibitor-associated myocarditis and im-mune checkpoint inhibitor-associated encephalitis,which could even seriously endangered the lives of pa-tients.Therefore,it was necessary for clinicians to fully understand and master the mechanism,clinical characteristics,laboratory and imaging examination characteristics,diagnostic criteria and differential di-agnosis conditions,and treatment principles of adverse reactions that may be caused by immune check-point inhibitors,so as to find a more optimized anti-tumor treatment regimen and actively prepared for the treatment of possible immune-related adverse reactions.In this paper,we reported a case of immune checkpoint inhibitor-associated severe pneumonia,referred to the relevant guidelines,introduced its clinical features,laboratory and imaging findings,difficulties encountered in the diagnosis and treatment process,briefly analyzed the causes,and reviewed the possibility of immune-related pneumonia should be considered when respiratory symptoms occurred in patients receiving immunotherapy;the increased ratio of blood neutrophil count to lymphocyte count,and the increased ratio of eosinophil count to lymphocyte count could be used as indicators to indicate immune-related adverse reactions in patients;bronchoalveo-lar lavage fluid examination and bronchoscopy and lung biopsy were helpful for the diagnosis;when im-mune checkpoint inhibitor-associated severe pneumonia occurred,in addition to symptomatic and sup-portive treatment,adequate glucocorticoid-based immunosuppressive therapy should be given in time,and combined with cytokines monoclonal antibodies and other biological agents,immunoglobulin co-therapy,but the current indications for the use of biological agents were not fully clear,and the use of high-dose immunosuppressive drugs might cause the risk of severe infection.Therefore,according to the relevant literature and the findings in the process of clinical diagnosis and treatment,this paper proposed that the serum levels of IL-6,TNF-α,CRP and other inflammatory mediators in patients may be used as a quantitative indication to initiate biological agent therapy and accumulate experience for better solving similar problems in the future.