1.Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells
Meng-yang CHEN ; Rui-ping HUAI ; Dan-ni YANG ; Li-jie LEI ; Qiu-lin PU ; Li-li XIONG
Acta Pharmaceutica Sinica 2024;59(2):368-373
This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (
2. Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT
Shi-Qin YIN ; Rui-Han WANG ; Gui-Xuan YOU ; Si-Yi YANG ; Ying-Qiu YANG ; Rui-Han WANG ; Lei ZHANG ; Lei ZHANG
Acta Anatomica Sinica 2024;55(1):82-87
Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.
3.Cytoplasmic light-chain immunofluorescence combined with FISH in bone marrow smears to detect cytogenetic abnormalities in multiple myeloma
Yu SHI ; Hui YANG ; Rui GUO ; Zhen GUO ; Jianyong LI ; Yujie WU ; Hairong QIU
Chinese Journal of Hematology 2024;45(6):566-570
Objective:To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) .Methods:42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ].Results:In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively ( P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively ( P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion:The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.
4.Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients
Rui ZHENG ; Zifeng LIU ; Zhuanggui CHEN ; Xuekun HUANG ; Peiying FENG ; Huijun QIU ; Yaxin LU ; Jingjing CHEN ; Yana ZHANG ; Jianrong ZHANG ; Qintai YANG
Chinese Journal of Preventive Medicine 2024;58(6):791-798
Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.
5.The Optimal Storage Condition and Storage Time of Umbilical Cord Blood from Collection to Preparation
Rui GUO ; Jun-Ye YANG ; Ya-Bin ZHANG ; Xue-Ping HE ; Yong ZHANG ; Jun-Ling HAN ; Wen-Ling YANG ; Lu-Gui QIU
Journal of Experimental Hematology 2024;32(2):577-582
Objective:To explore the optimal storage condition and time of umbilical cord blood from collection to preparation.Methods:Collect cord blood samples from 30 healthy newborns,with each new born's umbilical cord blood was divided into two parts on average.One part was stored in cold storage(4 ℃)and the other was stored at room temperature(20-24 ℃).Samples were taken at 24,36,48,60 and 72 h,respectively,total nucleated cells(TNC)count and TNC viability was analyzed.Flow cytometry was used to detect the ratio of viable CD34+cells to viable CD45+cells and viability of CD34+cells,and colony-forming unit-granulocyte-macrophage(CFU-GM)count was performed by hematopoietic progenitor cell colony culture.The change trend of each index over time was observed,and the differences in each index was compared between cold storage and room temperature storage under the same storage time.Results:The TNC count(r4℃=-0.9588,r20-24℃=-0.9790),TNC viability(r4℃=-0.9941,r20 24 ℃=-0.9970),CD34+cells viability(r4℃=-0.9932,r20-24℃=-0.9828)of cord blood stored in cold storage(4 ℃)and room temperature storage(20-24 ℃)showed a consistent downward trend with the prolongation of storage time.The percentage of viable CD34+cells(r4℃=0.9169,r20-24 ℃=0.7470)and CFU-GM count(r4℃=-0.2537,r20-24℃=-0.8098)did not show consistent trends.When the storage time was the same,the TNC count,TNC viability,CD34+cells viability and CFU-GM count of cord blood stored in cold storage were higher than those stored at room temperature.Under the same storage time(24,36,48,60 or 72 h),TNC viability in room temperature storage was significantly lower than that in cold storage(P<0.001),but TNC count,percentage of viable CD34+cells and CFU-GM count were not significantly different between room temperature storage and cold storage.When stored at room temperature for 24 h and 36 h,the viability of CD34+cells was significantly lower than that in cold storage(P<0.001,P<0.01),when the storage time for 48,60 and 72 h,there was no significant difference in the CD34+cells viability between room temperature storage and cold storage.Conclusion:It is recommended that cord blood be stored in cold storage(4 ℃)from collection to preparation,and processed as soon as possible.
6.Diagnosis and Risk Stratification of Acute Myeloid Leukemia,Myelodysplasia-Related
Hui YANG ; Rui GUO ; Yu SHI ; Chun QIAO ; Yan WANG ; Yu-Jie WU ; Hai-Rong QIU
Journal of Experimental Hematology 2024;32(5):1372-1376
Objective:To analyze the clinical and genetic characteristics of acute myeloid leukemia,myelodysplasia-related(AML-MR)patients and evaluate their prognostic risk stratification,to guide clinical treatment decisions and improve understanding of the biological characteristics and disease progression.Methods:The study analyzed cellular and molecular genetic information of 307 AML-MR patients,diagnosed based on clinical history,bone marrow morphology,cytogenetics,and molecular genetic abnormalities.The risk stratification followed the 2022 ELN guidelines.Results:57 cases(18.6%)met the AML-MR diagnostic criteria based on morphology and clinical history,110 cases(37.2%)met the AML-MR diagnostic criteria based on cytogenetic results,and 210 cases(74.5%)met the AML-MR diagnostic criteria based on molecular testing results.Among different type of mutations,ASXL1 mutation was the most frequent,followed by SRSF2 and BCOR mutations.Except for 2 cases with incomplete data that could not be classified.263(86.2%)of the 305 patients were classified as poor prognosis,20(6.6%)were classified as good prognosis group,and 22(7.2%)were classified as intermediate prognosis group.Conclusion:Molecular genetic information plays a crucial role in diagnosing AML-MR,highlighting the importance of genetics in diagnosis and prognosis.Most AML-MR patients fall into poor prognosis categories,necessitating early intensive and targeted therapy for better survival outcomes.
7.Carnosine attenuates OGD/R damage to BV2 cells by inhibiting ROS/NLRP3/GSDMD-mediated pyroptosis
Rui-Li RAN ; Yu-Tong WANG ; Jun-Qiu SONG ; Jiang BIAN ; De-Wei WANG ; Xiao-Han JIANG ; Fu-Lin YOU ; Jing YANG
Chinese Pharmacological Bulletin 2024;40(11):2150-2158
Aim To investigate the protective effect of carnosine on BV2 cell damage induced by oxygen-glu-cose deprivation/reperfusion(OGD/R)and its role in mediating pyrodeath through the ROS/NLRP3/GSDMD pathway.Methods BV2 cells were randomly divided into the control group(Con),model group(OGD/R),carnosine group(OGD/R+CAR),inhibitor group(OGD/R+MCC950),and carnosine+inhibitor group(OGD/R+CAR+MCC950).The cell survival rate was detected by MTT assay.The release rate of lactate dehydrogenase(LDH)in cell supernatant was detected by microenzyme labeling method.Cell damage was as-sessed using Hoechst 33342/SYTOX Green staining.ROS levels in cells were detected by DCFH-DA.The nucleation level of NF-κB p65 was observed by immu-nofluorescence.The protein expression levels of NLRP3,ASC,cleaved caspase-1,and GSDMD-N were detected by Western blot.The levels of IL-1 β and IL-18 in the supernatant were detected by ELISA.Results Com-pared with Con group,the survival rate of cells in the OGD/R group was significantly reduced,LDH release was significantly raised,cell morphology was damaged,and the positive rate of SYTOX Green was significantly elevated with ROS level in cells.The fluorescence in-tensity of NF-κB p65 in the nucleus increased,and the protein expression levels of NLRP3,ASC,cleaved caspase-1,GSDMD-N increased significantly,and the levels of IL-1 β and IL-18 in the cell superserum in-creased significantly.Compared with the OGD/R group,the survival rate of cells in other groups in-creased significantly,the LDH release rate significantly decreased,and the cell damage was improved to a cer-tain extent.The positive rate of SYTOX Green and ROS production in cells significantly decreased,and the fluorescence intensity of NF-κB p65 in nucleus markedly decreased.The expression levels of related proteins and the levels of IL-1 β and IL-18 in cell super-natant significantly decreased.Conclusion Carnosine can protect BV2 cells from OGD/R-induced damage by inhibiting oxidative stress and NF-κB activation,then inhibiting NLRP3/GSDMD signaling pathway.
8.Improvement of sleep by Jiawei Tianwang Buxin Dan and its mechanisms in simulated model of plateau exposure in rats
Jiaying HUANG ; Jingcao LI ; Yongfang GU ; Yumeng LIU ; Renhong QIU ; Yang ZHANG ; Rui XUE ; Shuo LI ; Huajin DONG ; Yanxin WANG ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(6):401-409
OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.
9.Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients
Rui ZHENG ; Zifeng LIU ; Zhuanggui CHEN ; Xuekun HUANG ; Peiying FENG ; Huijun QIU ; Yaxin LU ; Jingjing CHEN ; Yana ZHANG ; Jianrong ZHANG ; Qintai YANG
Chinese Journal of Preventive Medicine 2024;58(6):791-798
Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.
10.Retrospective analysis of characteristics of acute poisoning cases over eight years in a Tertiary Hospital in Jiangxi Province
Yang LI ; Fen LIU ; Rui XU ; Zhiqiang QIU ; Bo YANG ; Xiaolong LUO ; Haiquan WU ; Liang HUANG
Chinese Journal of Emergency Medicine 2024;33(9):1297-1301
Objective:To explore the epidemiology and clinical characteristics of hospitalized patients with acute poisoning at the First Affiliated Hospital of Nanchang University in Jiangxi Province.Methods:Based on the electronic medical records management platform of the First Affiliated Hospital of Nanchang University, a retrospective analysis was conducted on hospitalized patients with acute poisoning based on ICD-10 disease codes from 2014 to 2021. The gender, age, residence, poison type, etiology, route of exposure, illness severity, diagnostic and therapeutic processes, hospital stay duration, and prognosis of patients were collected.Results:A total of 1 953 cases of acute poisoning were included, comprising 871 males (44.6%) and 1 082 females (55.4%). The age was (42.7±20.0) years, with 113 fatalities (5.8%). Urban residents accounted for 706 cases (36.1%) and rural residents for 1 247 cases (63.9%). The highest incidence occurred in the 41-60 age group. Suicide was the primary cause, constituting 1 318 cases (67.5%), followed by accidental ingestion or contact, with overdose being less frequent. Oral poison way was the predominant route (1 681 cases, 86.1%), followed by inhalation and contact. Pesticide poisoning was the predominant type of poisoning in this study, with 847 cases (43.4%), followed by drug poisoning and foodborne poisoning. Pesticide poisoning predominated among rural residents (79.2%), while drug poisoning was more prevalent among urban residents (53.5%).Conclusions:In this study, patients with acute poisoning exhibited predominantly female gender, hailed from rural areas, and primary etiology of poisoning was pesticide ingestion for suicidal intent. Targeted education and control measures should be carried out for the above high-risk areas, populations and poisons.

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