Lung cancer remains one of the most prevalent and lethal malignancies worldwide. The advancement of its precise diagnosis and therapeutic development urgently requires in vitro models that can highly recapitulate the pathophysiological characteristics of human tissues. Organ-on-a-chip has emerged as a novel technological platform that integrates microfluidic engineering, biomaterials, and other engineering strategies with organoid culture. This platform enables precise control over the cellular microenvironment, thereby closely mimicking the three-dimensional structure and physiological functions of human organs in vitro. Organ-on-a-chip systems demonstrate significant advantages in cancer research, developmental biology, and disease modeling, as they not only preserve the heterogeneity and pathological features of patient samples but also support co-culture of various cell types to reconstruct the tumor microenvironment (TME). However, standardized construction methods and integrated analytical strategies for this technology in lung cancer research remain to be further refined. This review systematically elaborates on the key technical principles of organ-on-a-chip and its recent advances in lung cancer modeling, drug screening, and immunotherapy research. It aims to provide a theoretical foundation and technical perspective for promoting the deeper application of organ-on-a-chip in precision medicine and translational research for lung cancer.
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Humans ; Lung Neoplasms/drug therapy* ; Organoids/drug effects* ; Lab-On-A-Chip Devices ; Animals ; Tumor Microenvironment

Objective:To compare the differences in the safety, efficacy and protective effects of rabies vaccine using the current pre-exposure prophylaxis schedule in China (0-7-21 or 28) and the newly recommended immunization program of WHO (0-7), aiming to provide data support for modifying the related content of Technical Guideline for Human Rabies Prevention and Control. Methods:The mice were randomly divided into five groups, namely 0-7-21 group (3-injection regimen), 0-7 group (2-injection regimen), 0-14 group, 0-21 group and control group, according to the current 3-injection regimen (0-7-21) in China and the 2-injection regimen (0-7) recommended by WHO. The survival status of the mice was observed. The mice were weighed every five days to compare the safety of different immunization procedures. Rabies virus neutralizing antibodies (RVNA) were detected 7, 14, 21, 28 and 35 d after the initial immunization. On day 35, the mice in each group were challenged with lethal dose of CVS-11 rabies virus to evaluate the protective effects of different pre-exposure immunization procedures.Results:There was no significant difference in weight gain of mice after vaccination. The positive rate of RVNA was 100% in all immunized groups from day 14, which could provide complete protection to mice. There was a significant difference in RVNA levels between 0-7-21 and 0-7 groups at 35 d( P<0.05), but there was no statistical difference at other time points ( P>0.05). RVNA level had a significant difference between 0-7 and 0-21 groups at 21 d and 35 d ( P<0.05). There was no statistical difference in RVNA level between other groups at each time point ( P>0.05). In the protective test, the survival rates of mice in all immune groups were 100%. Conclusions:The current 3-injection pre-exposure immunization procedure for rabies vaccine (0-7-21) and the newly recommended 2-injection immunization procedure (0-7) had similar efficacy and protective effects in animal tests. In view of the cost saving and better compliance of the 2-injection immunization procedure, it was recommended that relevant departments should conduct clinical trials as soon as possible to promote the implementation of this program.

Objective:To establish a rabies virus CVS-11 challenge model in BALB/c mice through intramuscular or intracerebral injection.Methods:The CVS-11 strain propagated in BSR cells with a titer of 2.7×10 7 FFU/ml was serially diluted 10 -1-10 -7 times to infect 4-week-old female mice through intramuscular or intracerebral injection. The morbidity and mortality of mice were observed after virus challenge. Moreover, brain tissues of all challenged mice were subjected to direct immunofluorescence assay (DFA) and reverse transcription polymerase chain reaction (RT-PCR) to analyze the cause of death. The median lethal doses (LD 50) in mice under different challenge methods were determined. Mouse challenge models were established to evaluate the immunoprotective effects of four domestically available rabies vaccines on mice after CVS-11 exposure. Results:BALB/c mice developed typical neurological symptoms and died 6-12 d after intracerebral challenge and the LD 50 was 18.3/0.1 ml. The mice intramuscularly challenged with CVS-11 showed clinical symptoms on 8-15 d and the LD 50 was 2.7×10 5/0.1 ml. DFA results showed that specific yellow-green fluorescence appeared in the brain tissue prints of all dead mice. RT-PCR results showed that all amplified products showed bright bands at about 250 bp. These results suggest that rabies virus infection was the cause of death in mice. The protective effect test results of four different rabies vaccines on the market without immunoglobulin application showed that the survival rate of mice after exposure to one of the vaccines was 50%, and the survival rates of mice immunized with the other three vaccines were all 30%. The above results indicated that the four rabies vaccines provided partial protection for mice exposed to CVS-11 without the use of rabies passive immunization preparations. Conclusions:This study established rabies virus CVS-11 challenge models in BALB/c mice under different challenge methods and provided a technical platform for related research on rabies and rabies vaccines.