1.Role of circCCDC138 in early malignant transformation of human lung epithelial cells induced by carbon black nanoparticles
Runfeng LI ; Lichun MA ; Shulin QIN ; Wen LIU
Journal of Environmental and Occupational Medicine 2025;42(4):475-481
Background With the large-scale production and application of carbon black nanoparticles (CBNPs), occupational and general exposure is obviously increasing. Related studies have shown that exposure to CBNPs can induce oxidative stress, inflammation, and DNA damage. Objective To establish a CBNPs-induced malignant transformation (C-BEAS-2B) model of human lung epithelial cells (BEAS-2B) and explore the role and mechanism of circCCDC138 in the malignant transformation process. Methods At 0, 10, 20, 40 and 80 μg·mL−1 CBNPs concentrations, cell viability was detected by CCK8 assay. BEAS-2B cells were exposed to 20 mg·mL−1 CBNPs for three months, and a malignant transformation model of BEAS-2B induced by CBNPs was constructed. The migration and invasion abilities of the cells were detected by cell scratch and Transwell assays. The expressions of circ-CCDC138 in BEAS-2B and C-BEAS-2B were detected by qRT-PCR, and its stability was verified by a digestive resistance test. A cell model with interference or overexpression of circCCDC138 was constructed, and the expression of circCCDC138 in the cells was detected by quantitative reverse transcription-PCR. The cell cycle and apoptosis were determined by flow cytometry. Western blot was used to analyze the expression of p53 protein. Results The CBNPs used in the experiment were spherical particles with a chain-like structure. In the 20 μg·mL−1 CBNPs group, the reduction in the viability of BEAS-2B cells was relatively small (10%). Compared with the control cells, the 20 μg·mL−1 CBNPs group showed more obvious cell migration and invasion at 24 h and 48 h, indicating that the exposure to CBNPs induced early malignant transformation of BEAS-2B cells (P<0.01). The circCCDC138 expression in C-BEAS-2B was upregulated in a time-dependent manner after exposure to CBNPs. Compared with the C-BEAS-2B cells, the C-BEAS-2B cells over-expressing circCCDC138 exhibited arrested S phase progression (36.9%) and apoptosis resistance (P<0.01), along with down regulation of p53 protein expression in the cells (P<0.01), while the C-BEAS-2B cells interfering with circCCDC138 showed the opposite results (P<0.01). Conclusion BEAS-2B cells exposed to CBNPs (20 μg·mL−1) have significantly enhanced migration and invasion abilities, showing early malignant transformation characteristics. In addition, circCCDC138 is highly expressed in C-BEAS-2B cells with RNase R digestive resistance and increases in a time-dependent manner with CBNPs exposure. More importantly, circCCDC138 may promote the induction of malignant transformation of cells by inhibiting p53 protein expression.
2.Comparison of vault measurements by Scansys, Pentacam, CASIA and Arcscan after ICL implantation
Bo ZHANG ; Hao WANG ; Chenjiu PANG ; Wenwen DU ; Zaohe SUN ; Jin LI ; Yuwei GU ; Shulin WANG ; Qi FAN
Chinese Journal of Experimental Ophthalmology 2024;42(4):354-360
Objective:To evaluate the consistency of the Chinese three-dimensional anterior visual field analysis system (Scansys), the anterior segment analyzer (Pentacam), the frequency-domain anterior segment optical coherence tomography system (CASIA SS-1000), and a new ultra-high frequency digital ultrasound scanning system (Arcscan Insight100) to measure central vault after implantable collamer lens (ICL) implantation in myopic eyes with crystalline lenses.Methods:A diagnostic test study was conducted.Fifty-six myopic patients (56 eyes) who underwent ICL V4c implantation from June to December 2019 were included.Scansys, Pentacam, CASIA and Arcscan were used to measure the central vault after surgery.The vault measurements were compared.Correlations between the measurements of the four instruments were analyzed using Pearson correlation analysis, and consistency comparisons were analyzed using the Bland-Altman method.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). Written informed consent was obtained from each subject.Results:The central vault measurements by Scansys, Pentacam, CASIA and Arcscan were (481.8±191.6), (476.4±190.6), (619.3±207.5) and (534.0±221.2)μm, respectively, with a statistically significant overall difference ( F=143.301, P<0.001). The vault measurements by Scansys and Pentacam were significantly lower than CASIA and Arcscan, and Arcscan was lower than CASIA, with statistically significant differences (all at P<0.001). There were strong positive correlations in vault measurements between Arcscan and CASIA, Arcscan and Pentacam, Arcscan and Scansys, CASIA and Pentacam, CASIA and Scansys, Pentacam and Scansys ( r=0.982, 0.933, 0.931, 0.942, 0.941, 0.989; all at P<0.001). Intraclass correlation coefficients of vault measurements by Scansys, Pentacam, CASIA and Arcscan were 0.985, 0.975, 0.998, 0.992, respectively.The 95% limits of agreement of vault measurements differences were -170 to 0, 0 to 280, 0 to 280, -110 to 210, -100 to 220 μm, between CASIA and Arcscan, CASIA and Scansys, CASIA and Pentacam, Arcscan and Scansys, Arcscan and Pentacam, respectively, and the maximum absolute value of the difference was beyond the clinically acceptable range, showing poor agreement.The 95% limits of agreement of vault measurement difference was -60 to 50 μm between Scansys and Pentacam, showing a good agreement. Conclusions:The repeatability of the vault after ICL V4c implantation in myopic eyes measured by the four instruments is good.Among them, the vault measurements of Scansys and Pentacam are smaller, showing good consistency, and their results could be substituted for each other.The measurement of CASIA is the largest, followed by Arcscan, which have a large difference from each other, and their results can not be substituted for each other, which should be comprehensively analyzed with the actual situation in clinical work.
3.Thromboelastography and routine coagulation tests in the management of coagulation during ECMO therapy:a comparative study
Hao LI ; Sina LI ; Huini HUANG ; Ziji YANG ; Huiqiong XIE ; Ruixian LUO ; Shulin XIANG ; Hailan LI ; Zhuning MO
Chinese Journal of Blood Transfusion 2024;37(6):613-619
Objective To investigate the correlation and consistency between the parameters of thromboelastography(TEG)and routine coagulation tests,and to evaluate the application value of the two methods in heparin anticoagulation monitoring and coagulation function monitoring in patients receiving extracorporeal membrane oxygenation(ECMO)therapy.Methods A total of 138 patients who recieved ECMO in the Department of Critical Care Medicine of the People's Hospital of Guangxi Zhuang Autonomous Region from October 2021 to December 2022 were selected.A total of 317 pairs of ordinary TEG and heparinase-modified TEG(hmTEG)parameters measured simultaneously were analyzed for correlation and consis-tency with activated partial thromboplastin time(APTT),fibrinogen(Fib),and platelet count(Plt),and the parameters tested when ECMO was established and 24 hours after ECMO operation were compared.Results The correlation coefficient between R values and APTT of hmTEG(r=0.441,P<0.05)was lower than that of ordinary TEG(r=0.547,P<0.05).The parameters α-Angle and K value of ordinary TEG were not correlated with Fib(P>0.05),while as for hmTEG,the correla-tion was 0.359(P<0.05)and-0.343(P<0.05),respectively.The correlation between MA value of hmTEG and Plt was 0.456(P<0.05),which was much lower than its correlation with Fib(r=0.715,P<0.05).APTT and hmTEG had moderate agreement in judging the anticoagulant effect of UFH(P<0.05).Plt at 24 hours after ECMO was significantly lower than that at establishment of ECMO(P<0.05).Fib,APTT and hmTEG parameters were not significantly different between the two groups(P>0.05).Conclusion The parameters of hmTEG can better reflect the real level of coagulation factors in patients receiving ECMO.The results of hmTEG and APTT are complementary to assess whether heparin in ECMO patients is over-dosed,and hmTEG has unique advantages.Routine coagulation tests and TEG cannot replace each other,and the combina-tion of them can achieve better anticoagulation and coagulation management.
4.Clinic information,pathological,and imaging characteristics in 2 058 surgical patients with lung cancer from a single center
Bingqing LONG ; Zeng XIONG ; Shulin LIU ; Yuanda CHENG ; Min LI ; Weihua LIAO
Journal of Central South University(Medical Sciences) 2024;49(2):247-255
Objective:Lung cancer is characterized by its high incidence and case fatality rate.Factors related to population composition and cancer prevention programme policy have an effect on the incidence and diagnosis of lung cancer.This study aims to provide scientific support for early diagnosis and treatment of lung cancer by investigating the clinic information,pathological,and imaging characteristics of surgical patients with lung cancer. Methods:The data of 2 058 patients,who underwent surgery for lung cancer in the Department of Thoracic Surgery of Xiangya Hospital of Central South University from 2016 to 2019,were retrospectively collected to analyze changes in clinic information,pathological,and imaging characteristics. Results:From 2016 to 2019,the number of patients per year was 280,376,524,and 878,respectively.Adenocarcinoma(68.1%)was the most common pathological type of surgical patients with lung cancer.From 2016 to 2019,the proportion of adenocarcinoma was increased from 55.5%to 74.1%.The proportion lung cancer patients in stage IA was increased from 38.9%to 62.3%,and the proportion of patients who underwent sublobar resection was increased from 1.8%to 8.6%.The proportion of lymph node sampling was increased in 2019.Compared with the rate in 2016,the detection rate of nodules with diameter≤1 cm detected by CT before surgery in 2019 was significantly improved(2.0%vs 18.2%),and the detection rate of nodules with diameter>3 cm was decreased(34.7%vs 18.3%).From 2016 to 2019,the proportion of lesions with pure ground-glass density and partial solid density detected by CT was increased from 2.0%and 16.6%to 20.0%and 37.3%,respectively.The proportion of solid density was decreased from 81.4%to 42.7%. Conclusion:The number of lung cancer surgery patients is rapidly increasing year by year,the proportion of CT-detected purely ground-glass density and partially solid density lesions are increasing,the proportion of patients with adenocarcinoma is rising,the proportion of early-stage lung cancer is increasing,smaller lung cancers are detected in earlier clinical stage leading to a more minimally invasive approach to the surgical methods.
5.Improved immune response and anti-tumor effect of WT1 peptide emulsion adjuvant vaccine for acute myeloid leukemia
Yan YE ; Zelong ZHANG ; Baohang ZHU ; Shulin LIU ; Zhen SONG ; Qingpeng YUAN ; Yun YANG ; Haibo LI ; Quanmin ZOU ; Hao ZENG ; Hongwu SUN
Journal of Army Medical University 2024;46(9):1024-1033
Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P<0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P<0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P<0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P<0.05)and the proportion of specific CD8+T cells(P<0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5%,while all mice in the other groups had died(P<0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.
6.A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness
Jie LIU ; Shuang LI ; Fan YANG ; Tianyu LI ; Rui LI ; Yousuf WAHEED ; Chen MENG ; Shulin LI ; Kun LIU ; Yanshan TONG ; Haisheng XU ; Chuankuo TIAN ; Xinglei ZHOU
The Korean Journal of Internal Medicine 2024;39(3):488-500
Background/Aims:
Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness.
Methods:
Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks.
Results:
The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group.
Conclusions
For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.
7.The role of roxadustat in chronic kidney disease patients complicated with anemia
Jie LIU ; Fan YANG ; Yousuf WAHEED ; Shulin LI ; Kun LIU ; Xinglei ZHOU
The Korean Journal of Internal Medicine 2023;38(2):147-156
The incidence of chronic kidney disease (CKD) is increasing worldwide and the current prevalence rate is 13.4%. There are > 120 million CKD patients in China and this number is expected to increase. One of the main abnormalities in patients with CKD and kidney impairment is decreased synthesis of erythropoietin (EPO), which causes anemia and affects iron metabolism. The probability of developing is higher in anemia patients with CKD than in the general population, and the incidence increases as kidney function decreases. Deficient EPO production by the kidney is the most important cause of renal anemia. Notably, anemia in patients with CKD has multiple causes, such as bleeding caused by platelet dysfunction, iron deficiency due to digestive and absorption disorders of the gastrointestinal tract, and shorter red blood cell life. Anemia is also a leading cause of hospitalization in patients with CKD. A new oral medication to treat renal anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor called roxadustat (FG-4592), regulates iron metabolism and promotes erythropoiesis. This drug has a therapeutic effect on patients with CKD. Roxadustat showed advantages over EPO in clinical experiments. This review summarizes the mechanisms of action, clinical applications, effectiveness, and safety of roxadustat.
8.Effect of botulinum toxin type A on children with odorihidrosis
Zeliang HE ; Julei ZHANG ; Jin LI ; Lingling LIU ; Chengliang ZHANG ; Yuanyuan YAO ; Zhenyang SUI ; Zeyi WU ; Shulin QIU ; Xiaodong LI
Chinese Journal of Medical Aesthetics and Cosmetology 2023;29(2):130-133
Objective:To investigate the effect of botulinum toxin type A on children with odorihidrosis.Methods:From March 2017 to February 2021, 121 children with odorihidrosis, including 48 males and 73 females, aged 13 to 17 (15.9±1.2) years, were admitted to the Burn and Plastic Surgery Department of the 980 Hospital of PLA. There were 24 cases in mild group, 50 cases in moderate group and 47 cases in severe group. Botulinum toxin A was injected into 20-50 points on each side, and 1 U was injected into each point. The total amount of botulinum toxin A was 50-100 U on both sides.Results:Three groups of children were evaluated for efficacy, 24 cases of mild group was significantly effective in 23 cases, accounting for 95.8%. In the moderate group, 46 (92.0%) of 50 cases showed obvious effect. 49 cases (98.0%) were effective; In the severe group, 40 cases (85.1%) showed obvious effect and 45 cases (95.7%) were effective. Three groups of children with different efficacy had no statistical significance ( P>0.05). The significant efficiency in mild and moderate groups was higher than that in severe group, and the difference was statistically significant ( P<0.05). Conclusions:Botulinum toxin type A is effective in the treatment of children with mild and moderate bromhidrosis, and is worthy of clinical application.
9.Small molecule inhibitors of RORγt for Th17 regulation in inflammatory and autoimmune diseases
Jiuping ZENG ; Mingxing LI ; Qianyun ZHAO ; Meijuan CHEN ; Long ZHAO ; Shulin WEI ; Huan YANG ; Yueshui ZHAO ; Anqi WANG ; Jing SHEN ; Fukuan DU ; Yu CHEN ; Shuai DENG ; Fang WANG ; Zhuo ZHANG ; Zhi LI ; Tiangang WANG ; Shengpeng WANG ; Zhangang XIAO ; Xu WU
Journal of Pharmaceutical Analysis 2023;13(6):545-562
As a ligand-dependent transcription factor,retinoid-associated orphan receptor γt(RORyt)that controls T helper(Th)17 cell differentiation and interleukin(IL)-17 expression plays a critical role in the pro-gression of several inflammatory and autoimmune conditions.An emerging novel approach to the therapy of these diseases thus involves controlling the transcriptional capacity of RORyt to decrease Th17 cell development and IL-17 production.Several RORyt inhibitors including both antagonists and inverse agonists have been discovered to regulate the transcriptional activity of RORyt by binding to orthosteric-or allosteric-binding sites in the ligand-binding domain.Some of small-molecule inhibitors have entered clinical evaluations.Therefore,in current review,the role of RORyt in Th17 regulation and Th17-related inflammatory and autoimmune diseases was highlighted.Notably,the recently developed RORyt inhibitors were summarized,with an emphasis on their optimization from lead compounds,ef-ficacy,toxicity,mechanisms of action,and clinical trials.The limitations of current development in this area were also discussed to facilitate future research.
10.Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis.
Yifei YANG ; Yi WANG ; Long ZHAO ; Fang WANG ; Mingxing LI ; Qin WANG ; Haoming LUO ; Qianyun ZHAO ; Jiuping ZENG ; Yueshui ZHAO ; Fukuan DU ; Yu CHEN ; Jing SHEN ; Shulin WEI ; Zhangang XIAO ; Xu WU
Chinese Herbal Medicines 2023;15(2):181-200
Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

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