Organoids are three-dimensional (3D) biological structures constructed in vitro by stem cells, which partially mimic the function of real organs. Brain organoids are an extremely important branch of organoid research. This technology can differentiate pluripotent stem cells into the required cell types in a 3D culture environment, and self-assemble into structural bodies, but it is currently unable to fully replicate the structural and physiological features of the real human brain. The maturity of brain organoids may form consciousness, which poses ethical issues such as determining moral status and informed consent in brain organoids research. This paper elaborated on the research progress and future development direction of brain organoids, and proposed multidimensional governance strategies for ethical issues faced in brain organoids research from the perspectives of ethical principles, ensuring public informed consent, and legal supervision. By exploring the above issues, reference will be provided for formulating ethical principles to guide the research and application of brain organoids in the future.

OBJECTIVE: To investigate the gene mutation occurved in AML patients with 29 kinds of fusion genes and 51 kinds of tumor gene. METHODS: Next-generation sequencing (NGS) was used to detected the 49 kinds of targeted gene. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutation were detected by DNA-based PCR and Sanger sequencing. Twenty-nine kinds of fusion genes were dected by multiplex nested RT-PCR. RESULTS: The total gene mutation rate was 91% (109/121) in all the 121 patients. On average, 2.1 mutated genes per patient were identified, among these 121 patients, coexistence of ≥ 3 mutations was frequent (34.7%). The most commonly mutated genes were NRAS (23.96%, n=29), followed by NPM1 (14.04%, n=17), CEBPA double mutations (14.04%, n=17), KRAS (11.57%, n=14)，FLT3-ITD (10.74%, n=13), CSF3R (10.74%, n=13), TET2 (9.92%, n=12) and IDH1 (9.1%, n=11). Overall, fusion genes were detected in 47 (37.3%) patients, including AML/ETO (n=12), CBFβ/MYH11 (n=11), PML/RARa (n=12), MLL rearranagement realated mutation MLL-X (n=10). TLS/ERG (n=1) and DEK/CAN (n=1) in an order of decreasing frequency. Patients with normal karyotype (NK)- AML exhibited more mutations in CEBPA, NPM1, TET2, RUNX1 and IDH1, comparing with abnormal karyotype patients. KRAS mutation in abnormal kayotype patients was significantly higher than that in normal kayotype patients (P=0.014). TP53 mutations were predominantly associated with complex cytogenetics (P=0.199). KRAS mutations were more frequent in core binding factor (CBF) acute myeloid leukemia (AML) and 11q23/MLL rearrangement leukemia, compared with NK-AML (P=0.006 and 0.003, respectively). KIT mutations predominated in CBF-AML (P=0.006). JAK2V617F mutations were detected in two patients and co-occurred with AML-ETO fusions. CONCLUSION At least one mutation is observed in more than 90% patients. On average, more than 2 mutated genes per patient are identified. Some gene mutations are associated with gene rearrangement.
Chromosomal Proteins, Non-Histone ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Oncogene Proteins ; Poly-ADP-Ribose Binding Proteins ; Prognosis

Objective To explore the quantitative expression of estrogen receptor(ER),progesterone receptor(PR)in breast hyperplasia and its Clinical significance.Methods The expression of ER and PR was examined by immunohistochemical S-P method and quantitative analysis technique in 20 cases a piece of epithelial hyperplasia of usual type,atypical hyperplasia(mild,moderate,severe)and intraductal carcinoma,which contrasted with 20 cases of usual breast.Results The difference of the expression of ER and PR between usual breast or epithelial hyperplasia of usual type and atypical hyperplasia or intraductal carcinoma was significant(P50%,there was significant difference between moderate dysplasia and mild dysplasia,but no significant difference between moderate dysplasia and severe dysplasia,intraductal carcinoma.Conclusions The abnormal expression of ER and PR may be an early event in the progression of breast carcinoma,it could be used for early diagnosis of breast premalignancy and as a effective mark to monitor the prognosis.

Objective: To investigate the protective effect and mechanism of JXHG Decoction on alcoholic liver injury.Methods: Each group of mice were fed for 30 days.Then 50% alcohol used to establish hepatic injury in mice by intragastric administration.16 hours later, the levels of TNF-α, AST, ALT in serum and MDA, GSH, TG, Caspase-3, Caspase-8 in liver were measured accordingly.Results: JXHG Decoction could reduce the levels of TNF-α, AST, ALT, MDA, TG, Caspase-3, Caspase-8, NF-κB and increase GSH, while alleviated tissue necrosis and aelipose degeration of hepar.Conclusion: JXHG Decoction has favorable anti-effects on alcoholic liver injury.Its possible mechanisms are reducing the inflammatory reaction by depressing the expression of TNF-alpha and NF-kappa B in liver cells, and alleviating the hepatic cell apoptosis induced by Caspase-8 and Caspase-3.

Objective To investigate and evaluate the detection and the variety of histology type constituent of the thyroid malignant tumor before and after universal salt iodization.Methods 1011 clinical pathological data of thyroid malignant tumor confirmed pathologically from 1961 to 2000 was retrospectively analyzed.The detection rate of thyroid malignant tumor,the constituent ratios of each histology type and the changes of age and sex distribution in main types of thyroid malignant tumor were determined.Results The total detection rate of thyroid malignant tumor after universal salt iodization (USI) (0.69%) were obviously increased compared with before universal salt iodization(0.46%,P40 years old) than before USI(≤40 years old).The incidence rates of thyroid malignant tumor in female patients were higher than male patients before and after USI.Conclusion The proportion and average age of thyroid malignant tumor increases after USI.The histological types of thyroid carcinoma have changes after USI:the proportion of PC increases obviously,the proportion of FC decreases accordingly.The average age of thyroid malignant tumor sufferers tends to increase and the peak ages of PC,FC and UC raise after USI.

OBJECTIVE To investigate the effect of succinate dehydrogenase complex subunit A (sdha)gene on cell proliferation,cell cycle and apoptosis of mouse hepatic cell line BNL CL.2 cells. METHODS The BNL CL.2 cells were transfected by two kinds of sdha-shRNA lentivirus to knockdown sdha gene. The infection efficiency of BNL CL.2 cells infected with lentiviral vectors was analyzed by flow cytometry. The expression of sdha gene and SDHA protein was detected by real-time PCR and Western blotting,respectively. The effect of sdha gene on cell proliferation of BNL CL.2 cells was examined by growth curve,while cell cycle and apoptosis were analyzed by flow cytometry. RESULTS The infection efficiency of BNL CL.2 cells in sh-control group and in sdha-shRNA group was above 80%. Compared with sh-control group,the expression of sdha gene in BNL CL.2 cells infected with sdha-shRNA lentivirus was decreased by about 20 times(P<0.01),the expression of SDHA protein was decreased by about 10 times(P<0.01),and the growth rate was about 70%that of sh-control group(P<0.05). The cells were arrested in S phase,and the percentage of cells in S phase was 0.74 times that of sh-control group(P<0.01). The percentage of cells in G0/GI phase was 1.17 times that of sh-control group(P<0.01). The percentage of cells in G2/M was 1.37 times that of sh-control group(P<0.01). But there was no obvious difference in the apoptosis rate. CONCLUSION The reduced expression of SDHA protein can inhibit the proliferation of mouse hepatic cells,and the inhibitory mechanism may be cell cycle arrest. There is possibly no relationship between inhibition and cell apoptosis.