Although cisplatin is a widely used chemotherapeutic agent, it is severely toxic and causes irreversible hearing loss, restricting its application in clinical settings. This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity. Here, we established in vitro and in vivo ototoxicity models of cisplatin-induced hair cell loss, and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death. In addition, we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA, which may act as a critical linker between the cyclic GMP-AMP synthesis-stimulator of interferon genes (cGAS-STING) pathway and the pathogenesis of cisplatin-induced hearing loss. H-151, a specific inhibitor of STING, reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo. This study underscores the role of cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
Cisplatin/toxicity* ; Animals ; Nucleotidyltransferases/antagonists & inhibitors* ; Membrane Proteins/antagonists & inhibitors* ; Signal Transduction/drug effects* ; Mice ; Hair Cells, Auditory, Inner/pathology* ; Antineoplastic Agents/toxicity* ; Mice, Inbred C57BL ; Hearing Loss/metabolism* ; Male ; Ototoxicity/metabolism*

The human serum proteome is closely associated with the state of the body. Endogenous peptides derived from proteolytic enzymes cleaving on serum proteins are widely studied due to their potential application in disease-specific marker discovery. However, the reproducibility of peptidome analysis of endogenous peptides is significantly influenced by the proteolytic enzymes within body fluids, thereby limiting the clinical use of the endogenous peptides. We comprehensively investigated the N and C terminus of endogenous peptides using peptidomics. The cleavage site patterns of the N and C terminus and adjacent sites from all the identified endogenous peptides were highly conserved under different sample preparation conditions, including long-term incubation at 37°C and pretreatment with repeated freeze-thaw cycles. Furthermore, a distinguishable cleavage site pattern was obtained when a different disease serum was analyzed. The conserved cleavage site pattern derived from proteolytic enzymes holds potential in highly specific disease diagnosis.
Carcinoma, Hepatocellular ; blood ; diagnosis ; Chromatography, High Pressure Liquid ; Chromatography, Reverse-Phase ; Humans ; Liver Neoplasms ; blood ; diagnosis ; Mass Spectrometry ; Nanotechnology ; Peptide Hydrolases ; metabolism ; Peptides ; blood ; Protein Structure, Tertiary ; Proteome ; analysis ; Proteomics ; Silicon Dioxide ; chemistry ; Time Factors

ObjectiveTo evaluate the effect of labor analgesia and the outcome of maternals and neonatals by applying the vitamin B6- folic acid mixture to combined with spinal-epidural analgesia(CSEA) in nulliparous women at latency.MethodsAll the 112 full-term nulliparous parturients were selected and divided into the treated group and controlled group.Nulliparous women in two groups received CSEA,with which the additional vitamin - folic acid mixture was used only in treatment group.The contrast between the analgesic effect in groups,and alalgesic effect-acting period,fentanyl Apgar score and newborn usage were compared between groups also.ResultsThe analgesic effect-acting period and fentanyl dosage in the treated group were significantly decreased.There was significant difference between the 2 ( P ＜ 0.05 ).ConclusionsIt could be effective applying vitamin B6- folic acid mixture at latency in nulliparous women based on CSEA,which could shorten the lumbar hemp effect-acting period and reduce fentanyl narcotic drugs dosage.

Objective To analyze the epidemiologieal features and treatment of brain injury in Chinese Wenchuan earthquake so as to provide the experiences for improving treatment level. Methods A total of 685 patients with earthquake-induced brain injury in the City of Deyang were collected to ana-lyze age, injury type, injury localization and treatment characteristics. Results Of large number of earthquake victims, the number of the patients with brain injury ranked the second place, mainly minor and moderate brain injuries involving scalp laceration for the most and skull fracture and extradural hema-toma for the next. As for the age distribution of the patients, young and middie-aged patients accounted for the most, for they were at school or at work when the earthquake happened. Obvious position distribu-tion features were found in depressed fracture of skull and extredural hematoma but not in the scalp lacera-tion. Depressed fracture of skull occurred mostly at forehead and occiput while extradural hematoma could be most seen at froutotemple. Most brain injuries were combined with other injuries. Mainly extremity and pelvic fractures. Conclusions Self-protection sense and measures during earthquake are very important for decreasing incidence and severity of brain injuries. The management of rospimtory tract in prehospital care should be strengthened to avoid asphyxia and hence raise the success rate of treatment.

The article discusses how to carry on case-based learning in the Marxist Philosophy Principle teaching.Case-based learning helps bring up students' ability in ponder,judgment,competition and innovation and is an important method that enhances students'ability to find,analyse and solve problems.It is also an important teaching method that strengthens the effect of Marxist philosophy Principle teaching.

The separation of anionic compounds by strong anion-exchange capillary electrochromatography (SAX-CEC) was carried out. It was found that the analytes could be absorbed onto the stationary phase, and this would lessen the retention factors (k) of the analytes, thus the column separation capability decreased. For the acidic compounds, k increased with increase of applied voltage. And the change of the applied voltage could provide different separation selectivity for the solutes. The separation with different eluent was studied. It showed that the logarithm of the capacity factor linearly decreased with increase of the logarithm of the ionic strength. The different retention behavior of the anionic compounds in SAX-CEC and CE was also studied