Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

OBJECTIVE：To invest igate the medication regulation of Tibetan medicine prescription of Punica granatum seeds， and to analyze the pharmaceutical property of it in the treatment of “Sanweihuo”（Me drod gusm) dysfunction induced-related diseases. METHODS ：Using Clinical Notes of Tibetan Medicine ，Medicine Standard of the Ministry of Public Health ：Tibetan Medicine as standard ，Tibetan medicine prescriptions of P. granatum seeds recorded in Sibu Yidian ，Yuewang Yaozhen and other medical records were collected ，and TCMISS V 2.5 software was used to analyze main indication and medicine frequency statistically. The core medicine combinations of the prescriptions were analyzed with Apriori algorithm （support degree ≥50％， confidence degree ≥90％)，and medication regulations were analyzed. Tibetan medicine “Ro Nus Zhu rJes ”vector model was used to analyze the properties of Tibetan medicine prescription of P. granatum seeds in the treatment of high frequency diseases ，and K-means cluster analysis was carried out for seventeen effectiveness. RESULTS ：A total of 300 Tibetan medicine prescriptions of P. granatum seeds were collected ，involving 104 kinds of main indications ，among which frequency of 18 kinds of indications was more than or equal to 10 times，including“non-indigestion syndrome ”（Ma Zhu ba) （76 times)，“wood cloth disease ”（Smug po) （46 times)，“edema”（Chu nad) （34 times)，etc. Totally 322 kinds of Tibetan medicines were involved. Among them ，21 flavors were more than or equal to 50 in frequency ，including Piper longum （192 times)，Amomum kravanh （164 times) and Carthamus tinctorius（134 times)，etc. Fifty-six core combinations were obtained ，mainly including P. granatum seeds-P. longum （192 times)， P. granatum seeds-A. kravanh （164 times) and P. granatum seeds-C. tinctorius （134 times). The prescriptions （13 pieces) with six flavors as pungent ，sweet and sour ，and with prominent medicinal properties such as roughness ，heat and dry effects could be used to treat “non-indigestion syndrome ”，and then included into type Ⅰ. The prescriptions （13 pieces) with six flavors as bitter ，sweet and pungent ，and with prominent medicinal properties such as cooling ，dull and heavy effects could be used to treat “wood cloth disease”，and then included into type Ⅱ. The prescriptions （11 pieces) with six flavors as sweet ，sour and pungent ，and with prominent medicinal properties such as dull ，heavy and moistening effects could be used to treat “edema”，and then included into type Ⅲ. CONCLUSIONS ：Tibetan medicine P. granatum seeds is often used in combination with the isothermal medicines such as P. longum ，A. kravanh . P. granatum seeds are also commonly found in cool prescriptions ，revealing that Tibetan medicine pays attention to “Sanweihuo”while treating diseases ，which embodies the academic thought of Tibetan medicine that “there is cooling in temperature ，and there is temperature in cooling ”.