1.KRT19 enhances the proliferation and chemoresistance of breast cancer cells by upregulating CDK1
Haiyun QIAN ; Fenghe CUI ; Jiangping HUANG ; Xianghui WANG ; Shengwei MA
Journal of Chinese Physician 2017;19(2):210-213
Objective To explore the role and mechanism of keratin 19 (KRT19) in breast cancer.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine KRT19 levles in 35 cases of breast cancer tissues and normal tissues.The correlation between KRT19 levels and clinical property of breast cancer was analyzed.Meanwhile,the expression levels of KRT19 in several breast cancer cells and mammary epithelial cell Michigan cancer foundation (MCF)-10A were evaluated by qRT-PCR assay.Over-expressed and knocked-down KRT19 in breast cancer ceils,3-(4,5-dimenthylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was performed to detect the proliferation and chemosensitivity of these cells.The ability of forming colon of these breast cancer cells with treated KRT19 was studied via colony-forming unit assays.Western blot assay was performed to determine expression levels of ceil cycler related proteins.Results KRT19 was upregulated in breast cancer tissues comparing to normal tissues.KRT19 was positively related to tumor node metastasis (TNM) stage and distant metastasis of breast cancer.Similarly,KRT19 was highly expressed in breast cancer cells compared to mammary epithelial cell MCF-10A.The proliferation and colony-forming ability was significantly enhanced in MCF-7 cell with o,verexpressed KRT19.MTS assay showed that chemosensitivity of MCF-7 cells with overexpression of KRT19 was much more remarkably reduced than the control group.However,knocking down KRT19 in breast cancer cells MDA-MB-231 got the opposite results.Western blot assay suggested that KRT19 could obviously upregulated cyclin-dependent kinase 1 (CDK1) but not p27 expression levels.Conclusions KRT19 was upregulated in breast cancer tissues and was positively related to TNM stage and distant metastasis of breast cancer.KRT19 can significantly enhance proliferation and chemoresistance of breast cancer cells via upregulating CDK1.
2.The relationship between gene polymorphism and serum expression of interleukin-10 with intracranial aneurysm
Deming SHAO ; Hong QIU ; Xiangdong YU ; Xianghui MA ; Yunchao LI ; Yujue WANG
Tianjin Medical Journal 2016;44(9):1112-1114,1115
Objective To analyze the associations of the interleukin-10 (IL-10) promoter-1082G/A and-819C/T single nucleotide polymorphism (SNP) and serum level of IL-10 with intracranial aneurysm (IAs). Methods The polymerase chain reaction (PCR) and DNA direct sequencing methods were used to detect IL-10 gene promoter district two SNP site,-1082G/A and-819C/T genotype frequency and allele frequency in 206 patients with IAs and 187 controls. Chi-square test was used to analyze differences between two groups. The serum level of IL-10 was analyzed by ELISA, and t-test was used to analyze significant differences between two groups. Results There were significant differences in genotypes of GG and GA+AA, as well as the alleles G and A, in-1082G/A locus between IAs group and control group (P<0.01). There were higher frequencies of genotype GA+AA and the allele A in IAs group than those in control group (P<0.01). There was higher risk of suffering IAs in patients with genotype GA+AA (OR=4.137, 95%CI:2.476-6.914) and the allele A (OR=3.368, 95%CI:2.476-4.583). There were higher frequencies of the genotype CT+TT and the allele T in-819C/T locus in IAs group than those of control group (P<0.01). There was higher risk of suffering IAs in patients with genotype CT+TT (OR=3.393, 95%CI:1.952-5.900) and the allele T (OR=3.764, 95%CI:2.730-5.192). The serum level of IL-10 was significantly lower in IAs group than that of control group (P<0.01). Conclusion The IL-10 promoter SNP influences the expression of IL-10. IL-10 promoter-1082G/A and-819C/T polymorphisms are correlated with the formation of IAs.
3.Co-delivery of CpG and antigen using hyaluronic acid bioconjugates-decorated nanoparticles to promote maturation and activation of dendritic cells
Mengmeng YAN ; Yijia LIU ; Xianghui ZHU ; Fengqiang CAO ; Hai WANG ; Guilei MA
International Journal of Biomedical Engineering 2018;41(5):373-379
Objective To study the maturation and activation effects of hyaluronic acid (HA) modified polymer nanoparticles co-delivering adjuvants and antigens on mouse bone marrow dendritic cells (BMDCs). Methods HA-modified polylactic acid-glycolic acid copolymer (PLGA) and cationic lipid DOTAP were used as nanocarriers (DOTAP-PLGA) to co-deliver adjuvant CpG with model antigen ovalbumin (OVA). In the drug-loaded nanocarriers, CpG was covalently bound to the surface of HA, and OVA was physically blended into DOTAP-PLGA nanocarriers. The nanoparticles were characterized by transmission electron microscopy and dynamic light scattering. The in vitro release of CpG and OVA in the nanoparticles was investigated. The uptake and distribution of nanoparticles in mouse BMDCs were studied by flow cytometry and laser scanning confocal microscopy. The maturation and cytokine expression of mouse BMDCs were evaluated by flow cytometry and enzyme-linked immunosorbent assay, respectively. Results The CpG-HA-OVA-PLGA nanoparticles loading CpG and OVA were prepared. The average particle size was (305.1±2.2) nm and the polydispersity index was 0.203. A core-shell structure of the nanoparticles modified by HA was clearly observed by transmission electron microscopy. Cellular experiment results showed that CpG-HA-OVA-PLGA nanoparticles could be efficiently uptaken by mouse BMDCs, and promote lysosomal release of CpG and cytoplasmic delivery of antigen OVA. Compared with free OVA group and free OVA+CpG group, the CpG-HA-OVA-PLGA nanoparticles significantly up-regulated the expression of co-stimulatory molecules CD86 and CD40 (all P<0.01), major histocompatibility complex I (MHC-I) (P<0.01), and cytokine tumor necrosis factor-α (TNF-α) (P<0.01). Conclusions HA-modified CpG and OVA nanoparticle co-delivery vectors can effectively promote the maturation and activation of dendritic cells, which provides a basis for the development of novel vaccine vectors for the co-delivery of antigens and adjuvants.
4.The application of deep hypothermic circulatory arrest in the surgical treatment of complex thoracoabdominal aortic aneurysm
Cong CUI ; Li ZHANG ; Xia GAO ; Xianghui ZHANG ; Kexiong SUN ; Changbo XIAO ; Gang WU ; Shen MA ; Yuxin CHEN ; Pingfan WANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(5):303-306
Objective To discuss the application of deep hypothermic circulatory arrest in surgical treatment of complex thoracoabdominal aortic aneurysms and its near-midterm effect.Methods The clinical data of 34 cases of thoracoabdominal aortic aneurysm in the center from August 2009 to June 2018 were analyzed retrospectively.All the patients underwent surgery under deep hypothermic circulatory arrest.There were 23 males and 11 females; aged 23 -67 years, mean(42.26 ±10.96) years old; Crawford type Ⅰ in 12 cases and Crawford type Ⅱ in 22 cases; aneurysms with a maximum diameter of 50 -120 mm, mean(65.26 ±16.09) mm;Marfan syndrome 15 cases, atherosclerosis 14 cases, aortic coarctation in 5 cases;22 cases of hypertension;28 cases of first aortic surgery, 6 cases of re-aortic surgery.Surgical transthoracic and abdominal incision, ext-racapsular approach, femoral artery and inferior vena cava intubation, deep hypothermic circulatory arrest technique to complete proximal anastomosis, arterial tube reconstruction of intercostal artery, abdominal organ blood supply artery and four The bifur-cated vessels were anastomosed, and the bifurcated vessels were anastomosed with the "Y"type artificial blood vessel trunk. The bilateral radial arteries were end-to-end anastomosis in the 10 mm artificial blood vessels of the "Y"type artificial blood vessels.Results There were no complications of cranial nerve system in the whole group , deep hypothermic circulatory arrest (17.68 ±4.88) min, ventilator assist time(34.88 ±16.04) hours, postoperative renal failure in 5 cases, after CRRT treat-ment After recovery, 1 case of paraplegia after operation, muscle strength recovered after cerebrospinal fluid drainage and de-compression, and 1 case died in the whole group, and died of multiple organ failure.The patients were followed up for 3 months to 5 years, and the results were satisfactory.The survivors did not die.The survivors did not die.However, 5 patients underwent thoracic aortic replacement under deep hypothermic circulatory arrest for the first time , and 4 patients underwent reo-peration because of distal vasodilation.The reconstructed intercostal artery occlusion occurred in 4 patients, but no paraplegia occurred.Conclusion When cross clamping the aorta is not feasible,it is safe to perform proximal anastomosis with deep hy-pothermic circulatory arrest.
5.The efficacy of external application of the Yuying powder combined with the Huanglian Shangqing pill in the treatment of subacute thyroiditis with cervical anterior pain as the main complaint and its impact on serum pain factors and oxidative stress levels
Xianghui YU ; Xiaoya REN ; Gengliang ZHANG ; Fengmei MA
Journal of Chinese Physician 2023;25(10):1490-1495
Objective:To analyze the clinical efficacy of the Yuying powder combined with the Huanglian Shangqing pill for the treatment of subacute thyroiditis (SAT) with cervical anterior pain as the main complaint, as well as its impact on serum pain factors and oxidative stress levels in patients.Methods:A prospective selection of 100 SAT patients with anterior cervical pain as the main complaint admitted to the Hebei Provincial Hospital of Traditional Chinese Medicine from January 2020 to May 2022 was conducted. They were randomly divided into two groups, with 50 patients in each group. The control group was treated with sustained-release diclofenac sodium tablets, while the observation group was treated with external application of the Yuying powder and internal administration of the Huanglian Shangqing pill. After 2 weeks of continuous treatment, the analgesic efficacy and adverse drug reactions of both groups were observed. The analgesic onset time of two groups of anterior cervical pain was compared. Two simplified McGill pain questionnaires before and after treatment [the SF-MPQ scores, including Pain Rating Index (PRI), Visual Analog Scale (VAS), and Current Pain Intensity (PPI) ], were compared; the traditional Chinese Medicine Syndrome Score, Serum Pain Factors levels [ tumor necrosis factor (TNF)- α, interleukin-1 β(IL-1β), prostaglandin E 2 (PGE 2), and nitric oxide (NO) ] and oxidative stress indicators [the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) ] were also compared. Results:The total effective rate of analgesia in the observation group [98.00%(49/50)] was significantly higher than that in the control group [82.00%(41/50)] ( P<0.05). The analgesic onset time in the observation group was significantly shorter than that in the control group ( P<0.05). After treatment, the scores of various components (PRI, VAS, PPI) and traditional Chinese medicine syndrome scores in the two groups of SF-MPQ were significantly reduced compared to before treatment (all P<0.05); and the decrease was more significant in the observation group (all P<0.05). After treatment, the serum levels of TNF -α, IL-1β, PGE 2, and NO in both groups significantly decreased compared to before treatment (all P<0.05), and the levels of serum pain inducing factors in the observation group were significantly lower than those in the control group (all P<0.05). After treatment, both groups showed a significant decrease in serum MDA content (all P<0.05), and a significant increase in serum SOD and GSH-Px levels (all P<0.05); And the improvement was more significant in the observation group (all P<0.05). The incidence of adverse reactions in the observation group [4.00%(2/50)] was lower than that in the control group [16.00%(8/50)] ( P<0.05). Conclusions:The overall efficacy of external application of Yuying powder combined with oral administration of Huanglian Shangqing pill in the treatment of SAT with cervical anterior pain as the main complaint is definite, and its effect may be related to significantly downregulating the expression level of serum related pain inducing factors in patients and reducing the level of oxidative stress in the body.
6.The effect of phased goal oriented liquid therapy on tissue perfusion and cognitive function in lung cancer patients undergoing radical surgery
Xianghui WANG ; Yongxue CHEN ; Xinbo WANG ; Xiaona WEI ; Manman MA ; Yan SUN ; Danqi REN ; Yanan LIU ; Yaning GUO ; Rui WANG
Journal of Chinese Physician 2024;26(1):43-47
Objective:To explore the effects of phased goal directed fluid therapy (GDFT) during anesthesia surgery on tissue perfusion and cognitive function in patients undergoing radical lung cancer surgery.Methods:A total of 108 lung cancer patients were prospectively selected and randomly divided into a control group and a study group using a random number table method. The control group received classical restrictive liquid therapy, while the study group received staged GDFT. We compared the surgical time, intraoperative blood loss, colloid fluid dosage, crystalloid fluid dosage, total output, and urine volume between two groups of patients; Two groups of patients were compared in terms of oxygenation index (OI), respiratory index (RI), central venous oxygen saturation (ScvO 2), lactate (Lac), central venous arterial carbon dioxide partial pressure difference (Pcv-aCO 2), oxygen supply index (DO 2I), and oxygen uptake rate (O 2ERe) before anesthesia induction (T 0), before single lung ventilation (T 1), 1 hour of single lung ventilation (T 2), immediate resumption of dual lung ventilation (T 3), 30 minutes of dual lung ventilation (T 4), and after surgery (T 5); The Mini Mental State Examination (MMSE) was used to evaluate the cognitive function scores of two groups of patients 1 day before surgery and 1 and 3 days after surgery, while recording the incidence of cognitive dysfunction (POCD) and pulmonary complications (including pulmonary infection, acute lung injury, pulmonary embolism, pulmonary edema, atelectasis, etc.) within 3 days after surgery. Results:The amount of crystal fluid and urine output in the research group was significantly lower than that in the control group, while the amount of colloidal fluid was significantly higher than that in the control group (all P<0.05). The OI of the study group T 1-T 5 was significantly higher than that of the control group, while the RI of T 2-T 5 was significantly lower than that of the control group (all P<0.05). The ScvO 2 of the study group T 1 to T 5 was significantly higher than that of the control group, and the Lac was significantly lower than that of the control group (all P<0.05); The MMSE scores of both groups of patients were significantly lower than those before surgery on day 1 and 3 after surgery, and the MMSE scores of the study group were significantly higher than those of the control group on day 1 and 3 after surgery (all P<0.05). The incidence of POCD within 3 days after surgery in the study group was 16.67%(9/54), lower than 37.04%(20/54) in the control group (χ 2=5.704, P=0.017); The incidence of pulmonary complications in the study group was lower than that in the control group (5.56% vs 22.22%, χ 2=4.955, P=0.026). Conclusions:The application of staged GDFT during anesthesia in patients undergoing radical lung cancer surgery can further improve tissue perfusion, improve microcirculation and oxygen supply-demand balance of systemic organs and tissues, including the brain, alleviate perioperative brain function damage, and reduce the occurrence of postoperative POCD compared to conventional liquid therapy.
7.Prospective cohort study of the association of cardiovascular disease with triglyceride glucose index and triglyceride glucose-related indicators
Shulin WANG ; Xianghui ZHANG ; Heng GUO ; Jia HE ; Xinping WANG ; Rulin MA ; Shuxia GUO
Chinese Journal of Epidemiology 2023;44(12):1943-1949
Objective:To investigate the association of cardiovascular diseases (CVD) with triglyceride glucose index (TyG) and TyG-related indicators in Uyghur populations of The Xinjiang Production and Construction Corps.Methods:Based on the cohort of the Uygur population of The Xinjiang Production and Construction Corps, 11 833 study subjects were included. The Kaplan-Meier method was used to estimate the cumulative incidence of CVD in each quartile of TyG and TyG-related indicators. Cox proportional hazards regression model was used to evaluate the relationship between TyG and CVD, TyG-related indicators and CVD. Framingham CVD risk score model (Framingham model) was used to evaluate whether the addition of TyG and TyG-related indicators could improve the predictive ability of the model. The potential mediating role of the TyG in the association between obesity and CVD was examined through mediation effect analysis.Results:The average age of the subjects was (37.00±13.67) years-old, and 51.0% were male. The median follow-up time was 5.67 years, with 1 288 CVD events. The cumulative incidence of CVD increased with the increase of TyG and TyG-related indicators quartiles, and compared with the Q1 group, the risk of CVD in the Q4 group of TyG, TyG-BMI, and TyG-WHtR increased by 20% ( HR=1.20, 95% CI: 1.01-1.42), 77% ( HR=1.77, 95% CI: 1.46-2.16) and 68% ( HR=1.68, 95% CI: 1.36-2.09), respectively. After adding TyG, TyG-BMI, and TyG-WHtR to the Framingham model, respectively, the model's area under the curve, net reclassification improvement, and integrated discrimination improvement were improved. In the association between BMI, WHtR, and CVD, the proportion of mediating effects mediated by the TyG index was 10.55% and 11.50%. Conclusions:Elevated levels of TyG and TyG-related indicators were strongly associated with the risk of CVD in the Uyghur population of The Xinjiang Production and Construction Corps, with TyG-BMI being the most closely correlated with CVD. Early monitoring of TyG-BMI helps identify high-risk groups of CVD.
8.Incidence and influencing factors of non-alcoholic fatty liver disease among rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps
Caiyin LI ; Shuxia GUO ; Yu LI ; Heng GUO ; Rulin MA ; Xianghui ZHANG ; Xinping WANG ; Yunhua HU ; Keerman MULATIBIEKE ; Shipeng GAO ; Jia HE
Chinese Journal of Epidemiology 2024;45(8):1149-1157
Objective:To investigate the incidence characteristics and influencing factors of non-alcoholic fatty liver disease (NAFLD) in rural Uyghur ethnic group residents in Xinjiang Production and Construction Corps and to provide scientific evidence for early identification and prevention of NAFLD for residents.Methods:A total of 10 158 participants were included from the Xinjiang Uygur ethnic group population cohort. A prospective cohort study and Cox proportional hazards regression model analysis were used to explore the influencing factors and clustering of NAFLD, and the dose-response relationship between related biochemical indicators and the risk of NAFLD was studied using a restricted cubic spline.Results:The cumulative incidence rate of NAFLD was 6.9%, and the incidence density of NAFLD was 12.06/1 000 person-years. The incidence density of NAFLD in females was higher than in males (14.72/1 000 person-years vs. 9.17/1 000 person-years, P<0.001). The incidence density of NAFLD gradually increased with age in the total population, both men and women (all P<0.001). In the general population, an education level of junior high school or above was a protective factor for NAFLD, while older age, divorce, widowhood, overweight, obesity, hypertension, increased glomerular filtration rate, decreased HDL-C, increased LDL-C, and increased ALT were risk factors for NAFLD. Estimated glomerular filtration rate (eGFR), HDL-C, LDL-C, and ALT were non-linearly correlated with the incidence of NAFLD, and there was a significant dose-response relationship between them. Only 19.1% of residents had no NAFLD risk factors; over 80.9% had ≥1 NAFLD risk factors. The risk of NAFLD increased with the number of risk factors. Conclusions:The incidence of NAFLD in rural Uygur ethnic group residents in Xinjiang Production and Construction Corps was relatively low, but most residents had one or more risk factors for NAFLD. Prevention and control of NAFLD in this population cannot be ignored. In addition, people of older age, divorced or widowed, low education level, overweight or obese, hypertension, and abnormal eGFR, HDL-C, LDL-C, and ALT were the high-risk groups of NAFLD that need to be paid attention to in this population.
9.The relationship between triglyceride glucose index and risk of cardiovascular disease among Kazakh and Uygur population in Xinjiang: a retrospective cohort analysis
Linzhi YU ; Rulin MA ; Xianghui ZHANG ; Jia HE ; Heng GUO ; Yunhua HU ; Xinping WANG ; Lati MU ; Yizhong YAN ; Shuxia GUO
Chinese Journal of Preventive Medicine 2022;56(6):800-805
Objective:To analyze whether triglyceride-glucose (TyG) index is associated with increased risk of cardiovascular diseases (CVD) and the value of TyG index in predicting CVD risk among Kazakh and Uighur population of Xinjiang.Methods:In this study, 5 375 Kazakh and Uygur people of Xinyuan county and Jiashi county were selected as the research objects. Subjects were divided into four groups based on the quartile of the TyG index level. Cox regression model was used to analyze the association between TyG index with the risk of CVD. The dose-response relationship between TyG index and CVD risk was described by restricted cubic splines. The area under the receiver operating characteristic curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to estimate the value of TyG index for predicting CVD. Mediating effect analysis was conducted to analyze the mediating effect of TyG index in the association between body mass index and CVD.Results:The age of subjects was 41.06(30.11,53.00)years old, with 46.30%(2 489/5 375)was male. After multivariate adjustment, there was an increasing trend between the risk of CVD and the higher TyG index Ptrend<0.001, compared with subjects of TyG index in Q1, the HR (95% CI) of Q2, Q3, and Q4 groups was 1.53, 1.23 and 1.73, respectively. Restricted cubic splines showed that TyG index was the linearly associated with the risk of CVD. TyG index could improve the prediction ability of Framingham model for the risk of CVD (NRI=0.106, P=0.010; IDI=0.003, P=0.030). The mediating effect analysis showed that in the relationship between body mass index and CVD, the TyG index had a mediating effect ( P<0.001), and the ratio of mediating effect was 12.69%. Conclusion:TyG index is an independent predictor of CVD risk among kazakh and Uygur population in Xinjiang and has a good predictive value for the risk of CVD.
10.Expression of signal recognition particle 14 in hepatocellular carcinoma and its relationship with disease progression and patient survival
Huimin TIAN ; Dongmei TANG ; Meilin MA ; Xianghui FU
Journal of Zhejiang University. Medical sciences 2024;53(4):460-471
Objective:To investigate the expression of signal recognition particle 14(SRP14)in hepatocellular carcinoma(HCC)and its clinical significance.Methods:The data of SRP14 expression in HCC were obtained from bioinformatics study,and from investigation with quantitative reverse transcription polymerase chain reaction(qRT-PCR),immunohistochemical staining and Western blotting in clinical samples.The Kaplan-Meier analysis was used to determine the associations between SRP14 mRNA expression and the overall survival,progression-free survival,and disease-specific survival of HCC patients.The effect of SRP14 on the proliferation and migration of HCC cells were determined by EdU staining,MTS,Transwell and wound-healing assays.The potential mechanism for SRP14 regulating HCC was explored through Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analysis as well as qRT-PCR.Results:According to the data from GSE14520,TNMplot database and clinical samples,compared with paired tumor-adjacent tissues,non-paired tumor-adjacent tissues and normal tissues,the mRNA expression of SPR14 in HCC tissues was upregulated(all P<0.05).In clinical samples,compared with paired tumor-adjacent tissues,the protein expression of SPR14 in HCC tissues was increased(P<0.05).The increased mRNA expression of SRP14 was associated with good overall survival,progression-free survival,and disease-specific survival in HCC patients.SRP14 inhibited the proliferation and migration of HCC cells in vitro.According to the KEGG and GO enrichment analysis,in non-specific HCC,the genes co-expressed with SRP14 may predominantly regulate protein synthesis,processing,and transport,while in nonalcoholic fatty liver disease related HCC,the genes co-expressed with SRP14 could control multiple signaling pathways such as MAPK,cAMP,PI3K-Akt,and Wnt.Mechanistically,SRP14 up-regulated the mRNA expression of tumor suppressor gene GPRC5A in HCC cells(P<0.05).Conclusion:SRP14 may regulate HCC progression and influence patient prognosis.