1.Identification of a JAK-STAT-miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions.
Songyang LI ; Yongjie LIU ; Xiaofeng YIN ; Yao YANG ; Xinjia LIU ; Jiaxing QIU ; Qinglan YANG ; Yana LI ; Zhiguo TAN ; Hongyan PENG ; Peiwen XIONG ; Shuting WU ; Lanlan HUANG ; Xiangyu WANG ; Sulai LIU ; Yuxing GONG ; Yuan GAO ; Lingling ZHANG ; Junping WANG ; Yafei DENG ; Zhaoyang ZHONG ; Youcai DENG
Acta Pharmaceutica Sinica B 2025;15(4):1922-1937
The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.
2.Relationship between AT1-AA levels in uterine fluid and the thickness of endometrium in infertile women with chronic endometritis
Jiahui ZHOU ; Guifang YANG ; De SONG ; Yinan ZHANG ; Yao CHEN ; Xuemin LI ; Yana YU ; Yuhui SHI ; Wenli ZHU ; Xiaoli YANG
Chinese Journal of Obstetrics and Gynecology 2025;60(7):520-527
Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.
3.Experimental Evaluation of the Clinical Laboratory ELISA Assay Using A Randomization Quality Control Method for Indoor Quality Control
Zhijun GAO ; Jianjun LI ; Yin CAI ; Yana REN ; Mengchen XIE ; Lan ZHENG ; Guoping ZHOU
Journal of Modern Laboratory Medicine 2025;40(3):199-202
Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P<0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285~5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031~1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P>0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.
4.Effects of Moving Pattern on Dipping Thickness Distributions in Polymer Heart Valve
Haiyang WEI ; Zheng LI ; Qianwen HOU ; Yana MENG ; Liangwei ZHU ; Enhui HAN ; Jianjun HU ; Jianye ZHOU
Journal of Medical Biomechanics 2025;40(4):1012-1019
Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7%reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.
5.Relationship between AT1-AA levels in uterine fluid and the thickness of endometrium in infertile women with chronic endometritis
Jiahui ZHOU ; Guifang YANG ; De SONG ; Yinan ZHANG ; Yao CHEN ; Xuemin LI ; Yana YU ; Yuhui SHI ; Wenli ZHU ; Xiaoli YANG
Chinese Journal of Obstetrics and Gynecology 2025;60(7):520-527
Objective:To investigate the relationship between the level of angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) in the uterine fluid and the thickness of endometrium in infertile women with chronic endometritis.Methods:A case-control study was conducted to select 122 patients who underwent hysteroscopy and endometrial tissue biopsy at Assisted Reproduction Center, Taiyuan Central Hospital due to infertility from March 2023 to January 2024 as the study subjects. According to the results of hysteroscopy and endometrial tissue biopsy, the patients were divided into 52 cases in the infertility group with normal endometrium (NE infertility group) and the chronic endometritis combined with infertility group (CE infertility group) with 70 cases. Enzyme-linked immunosorbent assay was used to detect the level of AT1-AA in uterine fluid of the two groups. General clinical data, AT1-AA absorbance value of uterine fluid and uterine related indexes of the two groups were analyzed, and the correlations between AT1-AA level and the variation of indexes were analyzed.Results:Gravidity (median: 1 vs 1; Z=7.029, P=0.030) and parity (median: 0 vs 0; Z=12.258, P=0.002) in CE infertility group were higher than those in NE infertility group. There was AT1-AA in the uterine fluid, and the level of AT1-AA in CE infertility group was significantly higher than that in NE infertility group (median: 2.07 vs 1.44; Z=3.099, P=0.029). The endometrial thickness of CE infertility group was lower than that of NE infertility group (median: 6.0 vs 7.0 mm; Z=-2.179, P=0.029), and there were no statistical differences in other indexes between the two groups (all P>0.05). Further correlation analysis showed that there were no correlation between the level of AT1-AA in uterine fluid and parity, endometrial thickness, gravidity in NE infertility group (all P>0.05). However, the level of AT1-AA in uterine fluid of CE infertility group was positively correlated with parity (Spearman′s r=0.339, P=0.004), and negatively correlated with endometrial thickness (Spearman′s r=-0.499, P<0.001), but not correlated with gravidity ( P>0.05). Conclusions:AT1-AA is present in the uterine fluid of infertile women. The elevated level of AT1-AA in uterine fluid of infertile women with CE is related to the thinning of the endometrium.
6.Experimental Evaluation of the Clinical Laboratory ELISA Assay Using A Randomization Quality Control Method for Indoor Quality Control
Zhijun GAO ; Jianjun LI ; Yin CAI ; Yana REN ; Mengchen XIE ; Lan ZHENG ; Guoping ZHOU
Journal of Modern Laboratory Medicine 2025;40(3):199-202
Objective To evaluate the application of ELISA randomized quality control,and continuously improve the laboratory testing capacity and quality assurance,in order to gradually improve the application of randomized quality control to the daily testing of ELISA.Methods Collected the quality control data of KEHUA HBsAg,compared the difference between randomized quality control data and immobilized quality control data.Group comparison of randomization quality control between rows and columns.The randomized quality control data were analyzed retrospectively and the quality control chart was established by using the randomized quality control data.Analyzed and compared the lost-control situation of randomized quality control and immobilized quality control.Results Randomized quality control S/CO value(2.831±0.343)and immobilized quality control S/CO value(2.651±0.260)in the same microplate,the difference between two was statistically significant(t=5.970,P<0.05).The differences between randomized quality control and immobilized quality control in columns 2 to 8 were statistically significant(t=2.285~5.536,all P<0.05).There were no statistically significant differences between randomized quality control and immobilized quality control in column 9 to 12(t=0.031~1.605,all P>0.05).There was no statistically significant difference in randomization quality control among all lines(F=0.858,P>0.05).The randomized quality control data was used to establish a quality control chart.Within the time range of the collected data,the randomized quality control was out of control for 6 times,all were greater than+3s,and the loss of control rate was 4.72%(6/127).Fixed position quality control lost control 9 times during the same period,all of which were greater than+3s,with a loss of control rate of 0.61%(9/1 481).Conclusion The randomized quality control has a greater possibility to reflect the factors affecting all the samples on the microporous plate.Random quality control can be used to find possible systematic errors in testing.Randomized quality control can gradually be fully applied to daily indoor quality control,but the loss of control rate and coefficient of variation may increase.
7.Baicalein inhibits lipopolysaccharide-induced microglial activation via the AKT/GSK3 β pathway
Yan ZHAO ; Hui XU ; Yana FU ; Yuanyuan YUE ; Xuejie CHAI ; Yongzheng LI
Chinese Journal of Neuroanatomy 2025;41(1):73-79
Objective:To investigate the effects of baicalein on the protein kinase B(AKT)/glycogen synthase kinase 3β(GSK3β)pathway and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in lipopolysaccharide(LPS)-activated BV2 microglial cells.Methods:BV2 microglial cells were cultured and divided into control group,LPS-induced group,and LPS+Baicalein group.Molecular docking was conducted to verify the bind-ing affinity of baicalein to AKT.Western blot and immunofluorescence staining were used to assess the expression and phosphorylation levels of AKT,GSK3β,TNF-α,and IL-1β in activated BV2 cells.Results:Baicalein exhibited a strong binding affinity for AKT.Western blot results showed that LPS stimulation led to increased TNF-α and IL-1 βexpression and decreased phosphorylation of AKT and GSK3β in BV2 cells(P<0.05).After Baicalein treatment,TNF-α and IL-1 β expression significantly decreased,while AKT and GSK3β phosphorylation levels increased compared to the LPS group(P<0.05).Immunofluorescence staining results were consistent with those of Western blot.Conclusion:Baicalein inhibits the expression of TNF-α and IL-1 β in activated microglia,potentially through activation of the AKT/GSK3β pathway.
8.Baicalein inhibits lipopolysaccharide-induced microglial activation via the AKT/GSK3 β pathway
Yan ZHAO ; Hui XU ; Yana FU ; Yuanyuan YUE ; Xuejie CHAI ; Yongzheng LI
Chinese Journal of Neuroanatomy 2025;41(1):73-79
Objective:To investigate the effects of baicalein on the protein kinase B(AKT)/glycogen synthase kinase 3β(GSK3β)pathway and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1 β)in lipopolysaccharide(LPS)-activated BV2 microglial cells.Methods:BV2 microglial cells were cultured and divided into control group,LPS-induced group,and LPS+Baicalein group.Molecular docking was conducted to verify the bind-ing affinity of baicalein to AKT.Western blot and immunofluorescence staining were used to assess the expression and phosphorylation levels of AKT,GSK3β,TNF-α,and IL-1β in activated BV2 cells.Results:Baicalein exhibited a strong binding affinity for AKT.Western blot results showed that LPS stimulation led to increased TNF-α and IL-1 βexpression and decreased phosphorylation of AKT and GSK3β in BV2 cells(P<0.05).After Baicalein treatment,TNF-α and IL-1 β expression significantly decreased,while AKT and GSK3β phosphorylation levels increased compared to the LPS group(P<0.05).Immunofluorescence staining results were consistent with those of Western blot.Conclusion:Baicalein inhibits the expression of TNF-α and IL-1 β in activated microglia,potentially through activation of the AKT/GSK3β pathway.
9.Effects of Moving Pattern on Dipping Thickness Distributions in Polymer Heart Valve
Haiyang WEI ; Zheng LI ; Qianwen HOU ; Yana MENG ; Liangwei ZHU ; Enhui HAN ; Jianjun HU ; Jianye ZHOU
Journal of Medical Biomechanics 2025;40(4):1012-1019
Objective To explore the impact of different moving patterns during the dip-coating process on thickness distributions of polymer heart valves.Methods Based on the volume of fluid(VOF)multiphase flow model,the Eulerian wall-film(EWF)model,and dynamic mesh technology,the dip-coating manufacturing process of polymer heart valves were numerically simulated.The effects of vertical,horizontal,and circular moving patterns on flow characteristics of the surface impregnation liquid and liquid film distributions under self-rotation conditions of the models were mainly studied.Subsequently,seven identical test points were set on each valve leaflet to collect thickness data,and the coefficient of variation(CV)was calculated to evaluate the uniformity of the liquid film thickness.Given that the vertical and horizontal patterns had fewer moving planes,limiting the optimization space,the circular pattern(45°)with richer moving planes was selected as the basis for optimization,and comparative analysis of numerical simulation was conducted.Results In the vertical pattern,the peak CV was 0.461 3;in the horizontal pattern,the CV was 0.060 8;and in the circular pattern,the CV at 30°,45° and 60° were 0.457 5,0.272 8,and 0.255 6,respectively.After optimization,the CV for the circular pattern(45°)decreased to 0.052 5,representing an 80.7%reduction compared to the pre-optimization value.Conclusions The moving patterns significantly affect the uniformity of dip-coating thickness distributions.The horizontal pattern demonstrates the best uniformity,while the vertical pattern shows the poorest uniformity.The CV for the circular pattern decreases as the angle increases,with its uniformity between that of the vertical and horizontal patterns.Optimization of moving pattern parameters based on simulation results has improved the uniformity of thickness distributions.
10.Relationship between angiotensin Ⅱ type 1 receptor autoantibody levels in follicular fluid and follicular development in patients with PCOS
Yana YU ; De SONG ; Guifang YANG ; Yao CHEN ; Yinan ZHANG ; Xuemin LI ; Jiahui ZHOU ; Yuhui SHI ; Xiaoli YANG
Chinese Journal of Reproduction and Contraception 2024;44(9):922-929
Objective:To investigate the presence of angiotensin Ⅱ type 1 receptor autoantibodies (AT1-AA) in follicular fluid, and to investigate the correlation between AT1-AA levels and follicular development in follicular fluid of infertile patients with polycystic ovary syndrome (PCOS).Methods:A case-control study was conducted on 182 infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) at the Center for Reproductive Medicine of Taiyuan Central Hospital from June 2021 to October 2022. There were 80 cases in the fallopian tube factor group (tubal factor group) and 102 cases in PCOS infertility group (PCOS group). Univariate analysis was performed for the general data, ovulation induction indexes and embryonic laboratory indexes of the two groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of AT1-AA in follicular fluid on the day of oocyte retrieval. Pearson or Spearman was used to analyze the correlation between AT1-AA level and follicle development indexes, and multiple linear regression was used to adjust for interfering factors to analyze the correlation between AT1-AA level and embryonic laboratory indicators. Results:Body mass index [BMI, (25.29±3.25) kg/m 2], antral follicle count [AFC, 24.00 (17.00, 24.00)], basal serum teststerone [0.50 (0.36, 0.79) μg/L] and anti-Müllerian hormone [AMH, 4.92 (2.57, 8.28) μg/L] in PCOS group were significantly higher than those in tubal factor group [(23.01±2.92) kg/m 2, P<0.001; 15.00 (10.25, 19.00), P<0.001; 0.38 (0.20, 0.59) μg/L, P=0.019; 3.06 (2.19, 4.89) μg/L, P=0.006]. Moreover, the AT1-AA P/N value in follicular fluid in PCOS group [4.24 (2.07, 8.89)] was significantly higher than that in tubal factor group [2.96 (1.86, 4.84), P=0.027]. In addition, the age of menarche in PCOS group [13.00 (12.00, 14.00) years] was earlier than that in tubal factor group [14.00 (13.00, 15.00) years, P=0.007]. Prolactin level [12.09 (9.65, 16.64) μg/L] was lower than that of tubal factor group [16.27 (12.86, 20.94) μg/L, P=0.002], and there were no statistical differences in other indexes between the two groups (all P>0.05). Correlation analysis showed that the level of AT1-AA in follicular fluid of PCOS patients was negatively correlated with oocyte retrieval rate ( r=-0.159, P=0.019). The results of multiple linear regression analysis showed that AT1-AA level in follicular fluid was negatively correlated with oocyte retrieval rate ( β=-0.598, P=0.028) and normal fertilization rate ( β=-0.527, P=0.022) after adjusting for confounding factors. Conclusion:The level of AT1-AA in follicular fluid in PCOS patients is significantly higher than that in patients with tubal infertility, and is negatively correlated with oocyte retrieval rate and normal fertilization rate.

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