BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

Medical equipment, as an important indicator of smart hospital evaluation, plays a vital role in hospital operations. To ensure the safe and efficient operation of medical equipment, a reasonable performance evaluation system is indispensable. This study introduces a platform based on Internet of Things (IoT) technology that connects medical devices and collects data, achieving standardized and structured data processing, and supporting online operational supervision. Through the Delphi method, a performance evaluation system for large medical equipment is constructed, including 4 primary indicators and 22 secondary indicators. DICOM data acquisition devices are used to achieve functions such as efficiency analysis, benefit analysis, usage evaluation, and decision-making support for medical equipment. The study is still in its early stages, and in the future, it is expected to integrate more types of equipment, achieve rational resource allocation, and significantly impact decision-making for the development of public hospitals.
Internet of Things ; Delphi Technique

Objective:To explore sex and rural-urban differences in the associations of different blood pressure levels with the risk of prediabetes.Methods:We used a multi-stage stratified cluster random sampling method to investigate 21 637 residents aged ≥18 years from 10 survey areas in Hubei province in 2020. The data on questionnaire, physical measurements, and laboratory indicators of the participants were collected. The associations of different blood pressure levels with risk of prediabetes by sex and regions were analyzed using multivariate logistic regressions after complex weighting.Results:A total of 16 111 subjects were included. The prevalence (95% CI) of prediabetes, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and IFG complicated with IGT were 25.1% (14.4%-35.9%), 12.7% (3.2%-22.1%), 8.1% (6.3%-9.8%), and 4.4% (2.3%-6.5%), respectively. After multivariate adjustment, the risk of prediabetes, IFG, IGT, and IFG complicated with IGT increased with the increment of blood pressure (both P for trend <0.05). The positive dose-response relationships between blood pressure levels and risk of prediabetes were also significant among male, urban, and rural residents (both P for trend <0.05), and the interactions between sex and blood pressure showed significant associations for risk of prediabetes and IGT (both P for interaction <0.05). Conclusions:Higher blood pressure levels were associated with an increased risk of prediabetes. The association with prediabetes was stronger in males, but no significant difference was found between urban and rural residents. More distinctive and effective prevention and control strategies should be developed for different populations.

Background Acute retinal ischemia anoxic injury is common in eye disorders,such as acute glaucoma,central retinal artery occlusion and ischemic optic neuropathy,etc.This will cause retinal ischemia anoxic injury and induce retinal ganglion cells (RGCs) death in addition.Endogenous cannabinoid (CB) and its receptors are involved in the central nervous system injury,ischemia,inflammation,and poisoning and other physiological and pathological process.Objective This study was to investigate the effect of CB on RGCs damage induced by oxygen-glucose deprivation (OGD).Methods The eyeballs were obtained from 6-week-old normal C57BL/6J mice to prepare retinal frozen sectionsand the expression and distribution of cannabinoid receptors (CB1R and CB2R) in RGCs was detected by immunofluorescence staining.The eyeballs of ten newborn C57BL/6J mice (postnatal 0-3 days) were obtained after immersed by 75％ alcohol and the retinas were isolated in preeooling DMEM for the primary culture of RGCs.The cells were identified by detecting the expression of Brn3a,a marker of RGCs,with immunofluorescence staining.Then the cells cultured for 14 days were divided into normal control group (in complete culture medium+95％ air+5％ CO2) and OGD group (in glucose-free medium+95％ N2 +4％ CO2 + 1％ O2) for 20 hours.The mitochondrial damage and RGCs morphology changed were evaluated by JC-1 staining to observe the mitochondrial membrane potential change.SR141716A (CB1R antagonist,1 μmol/L),SR144528 (CB2R antagonist,1 μmol/L) and 5 or 10 μmol/L WIN 55212-2 (CB1R and CB2R agonist) were added,and the survival rate of RGCs was assayed MTT.Results CBR was positively expressed in various layers of normal mouse retinas.The cells in the normal control group showed uniform size and polygon in shape with the long and thin axons,and the expression of Brn-3a was seen in the cells.However,in the OGD group,cell shrinkage and fragments were found and most of the axons disappeared.The expression of Brn-3a was evidently weakened.The fluorescence intensity of JC-1 was evidently weakened in the OGD group compared with the normal control group,showing the reduce of mitochondrial membrane potential.MTT assay showed that the survival rate of RGCs was (100.00± 13.87)％,which was significantly higher than (89.52-± 18.16)％ in the normal control group (q =8.065,P =0.008).The mean survival rates of RGCs were (116.63±22.21)％ and (112.61 ±19.02)％ in the cells treated by SR141716A and SR144528,and that in the normal cells was (89.52 ± 18.16)％ in the OGD group,with significant differences between SR141716A-or SR144528-treated cells and normal cells (q =29.780,17.391;both at P＜ 0.01).Conclusions Hypoxia and glucose-free up-regulate the expression of CB and activate CB pathway.Inhibition of activation CBR process has a neuroprotection effect under the Hypoxia and glucose-free condition.

Optogenetics is a novel technique which combines optics with genetics.Using genetic means,a selected opsin protein is ectopically expressed in target neurons,which are then stimulated by light to moderate the neuronal circuit,as a consequence to regulate the animal's behaviors.Retinal degeneration like retinitis pigmentosa and aged macular degeneration causes visual impairment and eventual blindness.Optogenetics techniques have opened the door to creating artificial photoreceptors in the remaining retinal circuits of retinal degeneration retinas via gene therapy.However,there are still limitations in optogenetics technique,for example,potential risk in virus infection,the choice of target cells and the low visual resolution of the experiment animal.It has been reported that vision was successfully restored to a certain extent in animal model using optogenetics technique.With higher photosensitivity of opsin protein,longer activation kinetics and higher transfection efficiency of virus vector,optogenetics techniques' application in ophthalmology will be improved.

Objective To compare the differences between electronic lesion of pyramidal tract and internal capsule hemorrhage in establishing spastic rat models.Methods Experimental animals were randomly assigned into three groups:electronic lesion group (EL),internal capsule hemorrhage group (ICH) and control group (CON,n=28).Seven,14,21 and 28 d after each treatment,the general conditions of the rats and behavioral tests on them were recorded; and the gastrocnemius Hoffman reflex (H reflex) was detected; and the percentage of type Ⅰ muscle fiber in quadriceps femoris were examined by skeletal muscle myosin ATP staining.Results Rats in EL group and ICH group showed significant differences in behavioral tests as compared with CON group (P＜0.05); the duration of symptoms of neurological deficit was significantly longer in EL group than the other two groups (P＜0.05).In contrast to CON group,the amplitude of gastrocnemius H reflex in EL group and ICH group was increased and the latency of H reflex was decreased with significant difference (P＜0.05),which could be observed till 28 d and 14 d,respectively,after each treatment.The percentage of type Ⅰ muscle fiber in quadriceps femoris EL and ICH groups was obviously increased as compared with that in CON group (P＜0.05),which persisted to 21 and 14 d,respectively,after each treatment.Meanwhile,rats in EL group showed significant differences in behavioral test,gastrocnemius H reflex and percentage of type] muscle fiber in quadriceps femoris as compared with ICH rats (P＜0.05).Conclusion The muscle tone of EL rats is higher,and lasts longer than that ofICH rats.