1.The RNA binding protein QKI can promote gastric cancer by regulating cleavage of EMT-related gene transcripts to form circRNAs
Yi-Shuang CUI ; Xuan ZHENG ; Ya-Nan WU ; Yi-Han YAO ; Jun WANG ; Zi-Qing LIU ; Guo-Gui SUN
Chinese Pharmacological Bulletin 2024;40(8):1462-1473
Aim To study the proliferation,invasion and migration ability of Quaking(QKI)in gastric cancer(GC)via elucidating the molecular mechanisms associated with QKI in the occurrence and development of GC through bioinformatics.Methods Differential expression analysis of QKI was performed across vari-ous human cancer samples by merging data from the TCGA and GTEx databases.The correlation was ana-lyzed between QKI protein expression and tumor muta-tion burden(TMB)score,microsatellite instability(MSI)score,and ESTIMATE score,and the correla-tion was also explored between QKI protein expression and overall survival(OS),disease free survival(DFS),and progression free survival(PFS).EMT related genes that could encode DECircRNAs were ob-tained through bioinformatics analysis to construct a QKI-EMT-circRNAs regulatory network.The differenti-ally expressed circRNAs and EMT related genes in TMK1 cells were verified.The proliferation,invasion and migration ability of the QKI was studied by using the knockdown system.Results QKI was differential-ly expressed in the vast majority of tumors and was closely related to TMB,MSI,and tumor microenviron-ment(TME);QKI emerged as a high-risk factor for predicting OS,DFS,and PFS in individuals with com-mon human cancers.QKI regulated the splicing of 6 EMT related gene transcripts to form eight circRNAs,all of which were significantly associated with the prog-nosis of gastric cancer patients.Cell experiments showed that compared to normal gastric epithelial cells,only hsa_ccirc_0004015,CALD1,and CDK14 were down-regulated in TMK1 cells.Knocking down QKI inhibited the proliferation,invasion and migration ability of TMK1 cells.Conclusion QKI exerts regu-latory control over the transcription of six EMT-related genes,resulting in the formation of circRNAs,thereby promoting the pathogenesis and progression of GC.QKI is highly expressed in TMK1 cells,and knock-down of QKI can inhibit the proliferation,invasion and migration ability of TMK1 cells.
2.Regulation of Mitochondrial Metabolic Adaptation in Thermogenic Adipocytes
Xuan CUI ; Ting SHI ; Dong-Ning PAN
Chinese Journal of Biochemistry and Molecular Biology 2024;40(7):897-906
With the rapid development of economy and the improvement of human living standard,vari-ous metabolic disorders such as obesity,type 2 diabetes mellitus and non-alcoholic fatty liver disease have become important public health problems in China.Thermogenic adipocytes are rich in mitochondria and uncoupling protein 1(UCP1),which maintain mammalian core body temperature through the consump-tion of triglycerides and glucose and non-shivering thermogenesis.Since activated thermogenic adipocytes are believed to possess anti-obesity and anti-diabetes potential,they have attracted considerable research interests.Mitochondria,as highly functionally conserved organelles in thermogenic adipocytes,respond to alterations in thermogenic capacity through metabolic adaptation in the process of thermogenic activa-tion or inactivation.However,the dysfunction of mitochondrial metabolic adaptation in thermogenic adi-pocytes may result in thermogenic defects and even systemic metabolic disorders.Here,we summarize the recent progress in mitochondrial remodeling in thermogenic adipocytes,including mitochondrial dy-namics,phospholipid and cristae remodeling,and regulation of mitochondrial ROS and oxidative stress.The relevant regulatory factors are summarized,which will provide new insights into how mitochondria maintain thermogenic capacity in thermogenic adipocytes,aiming to help the development of pharmaceuti-cal drugs to activate adaptive thermogenesis for fighting against metabolic diseases.
3.In Vitro Amplification of NK Cells from Feeder Layer Cells Expressing IL-21
Zhen-Zhao XU ; Xue-Hua ZHANG ; Ling-Ping ZHAO ; Gao-Hua LI ; Tian-Tian CUI ; Xiao-Ling WANG ; Xuan LI ; Ru-Ge ZANG ; Wen YUE ; Ya-Nan WANG ; Guo-Xin LI ; Jia-Fei XI
Journal of Experimental Hematology 2024;32(5):1578-1584
Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P<0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.
4.Construction of a screening index system to identify preferred countries in China's international vaccine cooperation
Yin-Ge WU ; Yu-Xuan CUI ; Yang-Mu HUANG
Chinese Journal of Health Policy 2024;17(9):60-67
Objective:This study aims to develop a country prioritization index system for China's international vaccine cooperation,providing a screening tool and referenceindicators.Method:Based on the PESTEL analysis model,the indicator system was preliminarily determined through literature review and expert interviews.Additional expert consultations were conducted to refine and finalize this system.The weight of the indicators was determined using the Analytic Hierarchy Process(AHP).Result:A comprehensive screening index system for identifying preferred countries in China's international vaccine cooperation has been established.This indicator system covers 5 factors including economy,politics,society,technology,law,and regulations,with 15 secondary indicators and 34 tertiary indicators subdivided.Legal and regulatory factors received the highest weight(0.48),followed by economic(0.23),political(0.15),social(0.095),and technological(0.045).The authority of the experts and the coordination of their opinions were both deemed satisfactory.All judgment matrices in the AHP passed the consistency tests,affirming the reliability of the indicator weight results.Conclusion:The study has established an evidence-based and reliable index system for prioritizing countries in China'sinternational vaccine cooperation,providing references for the selection process.
5.Epidemic status of drinking-tea type endemic fluorosis in Inner Mongolia Autonomous Region in 2022
Xiaojuan YANG ; Yijun LIU ; Na CUI ; Xuan WANG ; Zili CHANG ; Chengxiang ZHAO ; Zhenlin LI
Chinese Journal of Endemiology 2024;43(6):461-466
Objective:To investigate the epidemic status of drinking-tea type endemic fluorosis (fluorosis for short) in Inner Mongolia Autonomous Region (Inner Mongolia for short), and to provide theoretical basis and basic data for formulation and evaluation of prevention and control measures.Methods:From May to October 2022, a cross-sectional survey was conducted in key areas (168 administrative villages in 6 leagues or cities) identified in the 2019 regional census with tea drinking habits, daily per capita intake of tea fluoride > 3.5 mg, and patients with skeletal fluorosis. The drinking condition of brick tea in 10 households of each administrative village was investigated, and the brick tea samples were collected to detect fluoride level. The prevalence of dental fluorosis in children aged 8 - 12 and skeletal fluorosis in adults aged 16 and older was investigated, and urine samples of patients with skeletal fluorosis were collected to detect urinary fluoride levels.Results:Totally 98.40% (1 657/1 684) of the households in the surveyed areas had a habit of drinking brick tea, with an annual per capita consumption of brick tea and a daily per capita intake of tea fluoride of 5.07 kg and 5.38 mg, respectively. The qualified rate of fluoride level in brick tea samples was 55.64% (922/1 657), the average fluoride level of all other brick tea varieties exceeded the national standard limit (300 mg/kg) except for black brick tea (291.08 mg/kg). Totally 2 747 children aged 8 to 12 were examined, with a detection rate of 13.91% (382/2 747) for dental fluorosis. The disease was mainly mild. There was no statistically significant difference in the detection rate of dental fluorosis among different age groups (χ 2 = 5.53, P = 0.238). Totally 71 708 adults aged 16 and older were examined, and the detection rate of skeletal fluorosis was 1.02% (734/71 708). Patients were mainly aged between 50 and 70 years old, and the condition in each age group was mainly mild. Totally 715 urine samples of skeletal fluorosis patients were collected and tested, and 55.24% (395/715) of the urine samples had fluoride levels higher than 1.6 mg/L. Conclusions:In Inner Mongolia, the proportion of high fluoride brick tea in endemic areas of drinking-tea type fluorosis is high. The detection rates of dental fluorosis in children and skeletal fluorosis in adults are relatively high. The prevention and control situation of drinking-tea type fluorosis is still serious.
6.A cross-sectional study of renal injury in human immunodeficiency virus infection/acquired immunodeficiency syndrome patients after antiviral therapy in Henan Province
Xuan YANG ; Zhongfeng CUI ; Chaoyang LIU ; Lin ZHANG ; Quanxi LI ; Yujiao NIU ; Xue ZHANG ; Xiaohua ZHANG ; Zhaoyun CHEN ; Qiong LI ; Jinjin LIU ; Yan SUN
Chinese Journal of Infectious Diseases 2024;42(7):395-402
Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.
7.Extracorporeal shock wave combined with stretching training for treatment of chronic plantar fasciitis: a randomized control study
Yonggang DOU ; Qiuyu CHEN ; Dayong XIANG ; Xuan LI ; Zhijin JIANG ; Zhuang CUI
Chinese Journal of Orthopaedic Trauma 2024;26(8):651-656
Objective:To investigate the clinical efficacy of extracorporeal shock wave (ESWT) combined with stretching training in the treatment of chronic plantar fasciitis.Methods:A prospective case-control study was conducted to include the patients with chronic plantar fasciitis who had been admitted to Department of Orthopaedic Trauma, Nanfang Hospital, Southern Medical University from June 2021 to June 2022. A SPSS random number generator was used to randomize the patients into an experimental group (receiving treatment with ESWT combined with stretching training) and a control group (receiving stretching training only). Shear wave elastography (SWE) was used to quantitatively evaluate the elastic modulus of the plantar fascia. The 2 groups were compared in terms of visual analogue scale (VAS) pain score, plantar fascia thickness, and elastic modulus of the plantar fascia in the patients at 12 weeks after treatment; the correlation between VAS pain score and elastic modulus of the plantar fascia was examined using Spearman analysis in the patients at 12 weeks after treatment.Results:This study included a total of 41 patients (52 feet), 20 males and 21 females with an age of (49.9±8.2) years. There were 16 left sides, 14 right sides and 11 bilateral sides affected. The course of the disease was 7.0 (6.0, 12.0) months. The 2 groups were comparable because there were no significant differences in the general data before treatment between them ( P>0.05). The VAS pain score at 12 weeks after treatment for the experimental group was 1.0 (1.0, 2.0) points, significantly lower than that for the control group [3.0 (2.0, 3.0) points] ( P<0.05). The elastic modulus of the plantar fascia at 12 weeks after treatment for the experimental group was (79.48 ± 17.65) kPa, significantly higher than that for the control group [(57.08 ± 14.16) kPa] ( P<0.05). However, there was no statistically significant difference between the 2 groups in the thickness of the plantar fascia at 12 weeks after treatment ( P>0.05). There was a significant correlation between VAS pain score and elastic modulus of the plantar fascia after 12 weeks of treatment ( r = -0.708, P<0.001). Conclusion:In the treatment of chronic plantar fasciitis, combination of ESWT and stretching training is more effective than stretching training only.
8.Analysis of potential categories of sexual behaviors among male students who have sex with men and the status of pre exposure prophylaxis use
Chinese Journal of School Health 2024;45(7):974-977
Objective:
To analyze the use of preexposure prophylaxis (PrEP) among male students who had sex with men (MSM) with different sexual behavior patterns using potential categories, so as to provide evidence for determining the use patterns of PrEP consistent with MSM.
Methods:
A questionnaire survey was conducted by proportional sampling method on MSM in 31 provincial administrative regions in mainland China from 20 October to 30 December 2021, a total of 1 040 students were selected for the study. Latent variable analyses were conducted on a total of seven sexual behavioral characteristics, including knowledge of sexual partner HIV infection, frequency of condom use, number of sexual partners, engaging in group sex, provision of commercial sex, use of sex aids, and history of sexually transmitted infections (STIs) in the past year. And demographic characteristics were analyzed by Logistic regression analysis. The rates of PrEP awareness, willingness to use and usage rate in different sexual behavior risk groups were investigated.
Results:
Student MSM could be divided into two potential category groups:a lowrisk behavior group (82.4%) and a highrisk behavior group (17.6%). The PrEP usage rate (15.8%) was higher in the highrisk behavior group, and the difference was statistically significant compared to the lowrisk behavior group (7.2%) (χ2=13.43, P<0.05). Student MSM residing in the northeast, south, and northwest of China, in the pilot city, and with a sex role of "0.5" (possible acceptance and insertion of sexual behavior) were more likely to be in the highrisk behavior group (OR=3.13, 3.07, 3.87, 2.22, 1.66, P<0.05).
Conclusion
Student MSM in highrisk and lowrisk sexual differs in the behavior of PrEP, and targeted interventions should be implemented to promote the use of PrEP and reduce HIV infection in this population.
9.Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS
Chen-Shan LÜ ; Yi-Xuan CAO ; Xiao-Xi MU ; Hai-Yan CUI ; Tao WANG ; Zhi-Wen WEI ; Ke-Ming YUN ; Meng HU
Journal of Forensic Medicine 2024;40(1):30-36
Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.
10.Mendelian randomization study on the association between rheumatoid arthritis and osteoporosis and bone mineral density
Ruiqi WU ; Yi ZHOU ; Tian XIA ; Chi ZHANG ; Qipei YANG ; Xuan ZHANG ; Yazhong ZHANG ; Wei CUI
Chinese Journal of Tissue Engineering Research 2024;28(23):3715-3721
BACKGROUND:Many clinical research observations have indicated a close association between rheumatoid arthritis and osteoporosis as well as bone mineral density(BMD).However,it remains unclear whether there is a causal genetic relationship between rheumatoid arthritis and the development of osteoporosis and alterations of BMD. OBJECTIVE:To assess the potential causal relationship between rheumatoid arthritis and osteoporosis as well as BMD using a two-sample Mendelian randomization approach,provide meaningful insights from a genetic perspective into the underlying mechanisms and offer a reference for early prevention of osteoporosis and improvement in the progression of the disease. METHODS:We conducted a study using data from publicly available genome-wide association studies databases to identify single nucleotide polymorphisms associated with rheumatoid arthritis as instrumental variables(P<5×10-8).The main outcomes of the study included osteoporosis and BMD at five different sites,including total body BMD,lumbar spine BMD,femoral neck BMD,heel BMD,and forearm BMD.The inverse variance-weighted method was used as the primary analysis method to evaluate causal effects.Weighted median,simple median,weighted mode and MR-Egger regression were used as supplementary analyses.Causal relationships between rheumatoid arthritis and the risk of osteoporosis and BMD were assessed using odds ratios(OR)and 95%confidence intervals(CI).Heterogeneity was assessed using Cochran's Q test and horizontal pleiotropy was evaluated using MR-Egger intercept tests. RESULTS AND CONCLUSION:The inverse variance-weighted analysis demonstrated a positive association between genetically predicted rheumatoid arthritis and osteoporosis(OR=1.123,95%CI:1.077-1.171;P=4.02×10-8).Heterogeneity test(P=0.388)indicated no significant heterogeneity among the single nucleotide polymorphisms.MR-Egger intercept(P=0.571)tests did not detect horizontal pleiotropy,and sensitivity analysis showed no evidence of bias in the study results.There was no causal relationship between rheumatoid arthritis and BMD at the five different sites.The total body BMD(OR=1.000,95%CI:0.988-1.012;P=0.925),lumbar spine BMD(OR=0.999,95%CI:0.982-1.016;P=0.937),femoral neck BMD(OR=1.001,95%CI:0.986-1.016;P=0.866),heel BMD(OR=0.996,95%CI:0.989-1.004;P=0.419),and forearm BMD(OR=1.063,95%CI:0.970-1.031;P=0.996)indicated no significant association.MR-Egger intercept analysis did not detect potential horizontal pleiotropy(total body BMD:P=0.253;lumbar spine BMD:P=0.638;femoral neck BMD:P=0.553;heel BMD:P=0.444;forearm BMD:P=0.079).Rheumatoid arthritis may contribute to the development of osteoporosis through the interaction between chronic inflammation and bone formation,resorption,and absorption.Additionally,the use of glucocorticoids and the presence of autoantibodies(such as anti-citrullinated protein antibody)in patients with rheumatoid arthritis showed associations with osteoporosis.Future research should focus on monitoring systemic inflammatory markers,standardized use of glucocorticoids,and regular screening for osteoporosis risk in patients with rheumatoid arthritis.


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