Aim To investigate the effects of leptin on ?1(Ⅰ) collagen mRNA expression and protein production, and the roles of Janus kinase/signal transducers and activators transcription(JAK/STAT) signaling transduction pathway in increased ?1(Ⅰ) collagen mRNA expression stimulated by leptin in activated hepatic stellate cells(HSCs).Methods Firstly, ?1(Ⅰ) collagen mRNA expression and protein production as well as JAK1 and STAT3 phosphorylation induced by leptin at different doses in a human HSC cell line, LX-2 were determined by RT-PCR, ELISA, and Western-blot.Secondly, the effects of JAK1 inhibitor AG490 on JAK1 phosphorylation and ?1(Ⅰ) collagen mRNA expression stimulated by leptin were detected by Western blot and RT-PCR. Thirdly, the roles of AG490 and transfection with STAT3 antisense oligonucleotide(STAT3-ASON) in STAT3 phosphorylation after leptin were detected by Western blot. Finally, the effect of transfection with STAT3-ASON on ?1(Ⅰ) collagen mRNA expression after leptin was measured by RT-PCR.Results Leptin increased ?1(Ⅰ) collagen mRNA expression and protein production in a dose-dependent manner in LX-2, reaching a maximal level at 80 ?g?L-1 leptin. In addition, phosphorylation of JAK1 and STAT3 after leptin exhibited a time-dependent effect. Besides, JAK1 inhibitor AG490 completely blocked JAK1 and STAT3 phosphorylation and increased in ?1(Ⅰ) collagen gene expression after leptin in LX-2. Transfection with STAT3-ASON blocked STAT3 phosphorylation and increased ?1(Ⅰ) collagen mRNA by leptin in LX-2.Conclusion Leptin had a direct action on liver fibrogenesis by stimulating ?1(Ⅰ) collagen mRNA expression and protein production in activated HSC, and JAK/STAT signaling transduction pathway was involved in the process. JAK1 inhibitor AG490 and transfection with STAT3-ASON blocked the transduction pathway effectively in LX-2. Leptin may be an important factor in the development of hepatic fibrosis. Activated JAK1 and STAT3 signaling in human HSC line provided a novel molecular target for therapeutic intervention of liver fibrosis.

Papillary thyroid carcinoma is one of the most common thyroid cancer subtypes. Although papillary thyroid carcinoma can be treated effectively with excision, microwave ablation, radioactive iodine and hormone replacement therapy, these ways are inefficient in reducing its morbidity, mortality and recurrence rates. Therefore, it is very important to seek the molecular mechanism of the occurrence and development of papillary thyroid carcinoma, to provide effectively early diagnosis, accurate treatment and better long-term prognosis for papillary thyroid carcinoma patients. This paper summarizes the molecular regulatory mechanisms of non-coding RNAs and their related signaling pathways in the occurrence and development of papillary thyroid carcinoma, in order to provide evidence for continued research of biomarkers for papillary thyroid carcinoma.

ObjectiveTo describe the neuropsychological development screening of 0‒2 years in Tongzhou from 2017 to 2021 so as to understand the status and trend of developmental delay （DD）. MethodsAnnual report data of 21 community health service centers in Tongzhou District from 2017 to 2021 were clustered， Chi square test was used to analyze the differences in positive rate and DD rate of children aged 0‒2 years with different ages and household registration， and Chi square trend test was used to analyze the linear trend of each age group and household registration. The Gesell test results in 762 children with developmental delay were analyzed， and Chi square test was used to compare the age distribution differences in gross motor， fine motor， language and personal-social behaviors. ResultsThe DD rate of children aged 0‒2 years in 2017‒2021 was 0.43％. A decreasing trend of DD rate in the 0‒ age group was observed （χ²=14.135， P<0.001）， while an increasing trend of DD rate in the 1‒ and <3 age groups was observed （χ²=5.375， P=0.020； χ²=5.558， P=0.018）. The DD rate of children aged 0‒2 years with Beijing household registration was higher （χ²=12.504， P<0.001）. The DD rate of gross motor was the highest in the 0‒ age group （64.60%）， the DD rate of language was the highest in the <3 age group （85.97%）， and a statistically significant difference of gross motor and language was separately found in the three age groups （χ²=183.061， P<0.001； χ²=78.450， P<0.001）. ConclusionAge and Beijing household registration are the influencing factors of DD for children aged 0‒2， and 0‒ years and <3 years are the critical periods for guidance and intervention to promote the development of gross motor and language abilities.

Objective : To investigate the regulatory effect of artemisinin derivative dihydroartemisinin ( DHA) on anti-tumor immune function of CD8 + T cells induced by non-small cell lung cancer ( NSCLC) cells . Methods: NSCLC A549 cells were divided into DMSO control group and DHA treatment group . A549 cells were treated with DMSO and DHA at different concentrations (25 , 50 and 100 μmol/L) , and the optimal concentration of DHA was selected to treat A549 cells for 0 , 24 , 48 and 72 h according to half maximal inhibitory concentrate (IC50 ) . CCK 8 method and colony formation test were used to detect the effect of DHA on the proliferation and colony formation ability of A549 cells . Peripheral blood mononuclear cells (PBMCs ) of healthy individuals were isolated by density gradient centrifugation . After monocytes were removed by adhesion method , A549 cells pretreated with mitomycin C were co cultured with PBMCs at 10:1 ratio . After 2 weeks , flow cytometry was used to detect the proportion of CD8 + T cells and the expression levels of perforin and granzyme B . Results : Compared with the control group , the proliferation inhibition rates of A549 cells increased after treatment with 25 , 50 and 100 μmol/L DHA for 24 h (P < 0.01) . The IC50 of DHA on A549 cells was 46.26 μmol/L. According to IC50 concentration analysis , the inhibi tion rates of A549 cells treated with 50 μmol/L DHA for 0 , 24 , 48 and 72h were 1 53% , 53.50% , 63.84% and 69.91% , and the cells inhibition rates of A548 cells increased compared with the previous ob servation time point , namely 0 , 24 and 48 h (P < 0.01) . The colony formation assay showed that the colony formation number of A549 cells in DHA treated group decreased compared with the control group (P < 0.01) . Flow cytometry results showed that compared with the control group , the proportion of CD8 + T cells induced by A549 cells in the co-culture system and the proportion of CD8 + T cells expressing perforin and granzyme B were higher in DHA pretreatment group(P < 0.01) . Conclusion DHA inhibits the growth of NSCLC cells and promotes anti tumor immune response of CD8 + T cells induced by NSCLC cells .

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People’s Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories’ results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample’s highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.