1.Curcumin Induces Cycle Arrest of Colon Cancer HCT116 Cells via JAK1/STAT1/p21 Pathway
Tianshuo LI ; Zuowu XI ; Wenjie DONG ; Denghui SHI ; Yunrong LIU ; Zidong LIN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):74-82
ObjectiveTo investigate the effect of curcumin on the cycle arrest of human colon cancer HCT116 cells and decipher the possible molecular mechanism. MethodThe methyl thiazolyl tetrazolium (MTT) method was employed to examine the effects of curcumin (0, 12.5, 25, 50, 75, 100 μmol·L-1) and 5-fluorouracil (5-FU, 600 μmol·L-1) on the proliferation of HCT116 cells at different time points (24, 48, 72 h). Flow cytometry was employed to examine the cycle of HCT116 cells treated with curcumin (0, 25, 50, 75 μmol·L-1) and 5-FU. Western blot was employed to determine the expression of proteins in the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 1 (STAT1) /cyclin-dependent kinase inhibitor 1A (p21) pathway in HCT116 cells. The binding of STAT1 to p21 promoter region was detected by chromatin immunoprecipitation (ChIP). Small interfering RNA (siRNA) was employed to measure the role of STAT1 in regulating the expression of p21 and that of JAK1 in regulating the activation of STAT1 by Western blot and cellular immunofluorescence, respectively. ResultCompared with the blank group, the HCT-116 cells treated with curcumin and 5-FU showed decreased viability (P<0.05), increased proportions of cells in the G0/G1 phase (P<0.05), decreased proportions of cells in the S phase and G2/M phase (P<0.05), down-regulated protein level of phosphorylated p21 (P<0.05), and up-regulated protein level of p21 (P<0.05). Compared with the curcumin group, the p21 siRNA+ curcumin group presented decreased proportion of cells in G0/G1 phase (P<0.05). Compared with the blank group, curcumin elevated the level of phosphorylated STAT1 (p-STAT1) (P<0.05). Compared with the curcumin group, the curcumin + STAT1 siRNA group showcased up-regulated protein level of p21 in HCT116 cells (P<0.05). The mechanism study showed that curcumin treatment enhanced the enrichment of STAT1 in the p21 promoter region (P<0.05) compared with the blank group. Compared with the blank group, curcumin up-regulated the level of phosphorylated JAK1 (p-JAK1) (P <0.05). Compared with the curcumin group, the curcumin + STAT1 siRNA group demonstrated up-regulated protein levels of p-STAT1 and p21 in HCT116 cells (P<0.05). ConclusionCurcumin may induce the cycle arrest of human colon cancer HCT116 cells by activating the JAK1/STAT1/p21 signaling pathway.
2.Prediction model related to 6-year risk of frailty in older adults aged 65 years or above in China
Jinhui ZHOU ; Li QI ; Jun WANG ; Sixin LIU ; Wenhui SHI ; Lihong YE ; Zhenwei ZHANG ; Zenghang ZHANG ; Xi MENG ; Jia CUI ; Chen CHEN ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Epidemiology 2024;45(6):809-816
Objective:To develop a prediction tool for 6-year incident risk of frailty among Chinese older adults aged 65 years or above.Methods:Data from the Chinese Longitudinal Healthy Longevity Survey from 2002 to 2018 was used, including 13 676 older adults aged 65 years or above who were free of frailty at baseline. Key predictors of frailty were identified via the least absolute shrinkage and selection operator (LASSO) method, and were thereafter used to predict the incident frailty based on the Cox proportional hazards regression model. The model was internally validated by 2 000 Bootstrap resamples and evaluated for the performance of discrimination and calibration using the area under the receiver operating characteristic curve (AUC) and calibration curve, respectively. The net benefit of the developed prediction tool was evaluated by decision-curve analysis.Results:The M( Q1, Q3) age and follow-up time of the participants were 81.0 (71.0, 90.0) years and 6.0 (4.1, 9.2) years, respectively. A total of 4 126 older persons (30.2%) were recorded with frailty incidents during the follow-up, with the corresponding incidence density of 41.8/1 000 person-years. A total of 15 key predictors of frailty were selected by LASSO, namely, age, sex, race, education years, meat consumption, tea drinking, performing housework, raising domestic animals, playing cards or mahjong, and baseline status of visual function, activities of the daily living score, instrumental activities of the daily living score, hypertension, heart disease, and self-rated health. The prediction model was internally validated with an AUC of 0.802, with the max Youden's index of 0.467 at a risk threshold of 19.0%. The calibration curve showed high consistency between predicted probabilities and observed proportions of frailty events. The decision curve indicated that higher net benefits could be obtained via the prediction model than did strategies based on intervention in all or none participants for any risk threshold less than 59%, and the model-based net benefit was estimated to be 0.10 at a risk threshold of 19.0%. Conclusions:The herein developed 6-year incident risk prediction model of frailty, based on easily accessible questionnaires and physical examination variables, has good predictive performance. It has application potential in identifying populations at high risk of incident frailty.
3.Issues and Solutions for Symptom Efficacy Evaluation in the Big Data Era of Traditional Chinese Medicine
Xiaoyu ZHANG ; Sichao TIAN ; Liangzhen YOU ; Xi GUO ; Zhao CHEN ; Chunling LIU ; Nannan SHI ; Hongcai SHANG
Journal of Traditional Chinese Medicine 2024;65(8):792-795
Emphasizing symptom efficacy is an important manifestation of the personalized diagnosis and treatment of traditional Chinese medicine (TCM). However, in current clinical practice of TCM, there are challenges such as diverse symptom expressions, difficulty in standardization, inconsistent evaluation standards for symptom efficacy, lack of universal quantitative methods, and complexity in collecting complete and accurate symptom information. These issues hinder the full and effective utilization of symptom information. Addressing the current research status and existing problems of symptom terminology standardization, quantification and grading of symptom efficacy, and collection of symptom information, this paper proposes methodological strategies for effectively recording and utilizing TCM symptom efficacy information in the era of big data. These strategies include collecting TCM symptom information based on patient reporting, standardizing the evaluation of TCM symptom efficacy from measurement scales and evaluation dimensions, integrating TCM symptom efficacy evaluation into clinical diagnosis and treatment processes, and utilizing artificial intelligence technology to acquire and process TCM symptom efficacy information. TCM symptom efficacy evaluation strategies based on patient perspectives and artificial intelligence technology will help fully explore the value of data elements, promote the objective demonstration of the specific efficacy of TCM, and facilitate the discovery of effective patterns.
4.The First Application of Domestically Produced Self-expanding Transcatheter Aortic Valve Controllable Bending Delivery System in China
Yang CHEN ; Guoliang CHEN ; Di SONG ; Hongliang ZHANG ; Moyang WANG ; Guannan NIU ; Zheng ZHOU ; Qian ZHANG ; Qingrong LIU ; Zhenyan ZHAO ; Jie ZHAO ; Bin ZHANG ; Dejing FENG ; Wence SHI ; Jicheng XI ; Yongjian WU
Chinese Circulation Journal 2024;39(3):285-289
A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.
5.Maggot alleviates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation
Hong YAO ; Kedi LIU ; Chengzhao LIU ; Weihong LI ; Qi DAI ; Shi ZHAO ; Ziheng DING ; Hefei WANG ; Xiaojing GE ; Peifeng WEI ; Jialin DUAN ; Miaomiao XI
Journal of Southern Medical University 2024;44(11):2121-2130
Objective To explore the therapeutic mechanism of maggot for psoriasis-like lesions in mice from the perspective of immune stress and complement activation regulation.Methods Thirty-six male C57BL/6 mice were randomly divided into control group,model group,maggot(1.25%,2.5%,and 5%)groups,and Benvitimod(1%)group.Psoriasis-like lesions were induced by application of imiquimod cream,and the severity of skin lesions was assessed using the modified Psoriasis Area and Severity Index(MPASI)score.Auricular swelling of the mice was observed,and histopathological changes of the skin lesions were examined with HE staining.Scratching behavior of the mice was observed and the spleen index was calculated.Toluidine blue staining was used to detect mast cells in the skin lesions,and serum levels of IgG,IgM,the complements CH50,C1s,C3,C3a,C5 and C5a,and the inflammatory factors IL-23,IL-17A and TNF-α were determined with ELISA.Results In mice with imiquimod-induced psoriasis-like skin lesions,treatment with the maggot at the 3 doses significantly decreased MPASI score,alleviated auricular swelling and pathologies in the skin lesions,reduced scratching behaviors,spleen index,and the number of mast cells in the lesions.Treatment with high-dose maggot significantly lowered serum levels of IgG,C1s,C3a,C5a,IL-23,IL-17A and TNF-α and the levels of C1s,C3,C3a,C5 and C5a in the lesion tissue,and increased serum levels of CH50,C3,and C5.The therapeutic effect of maggot showed a dose-effect dependence.Conclusion Maggot can alleviate psoriasis-like skin lesions in mice by inhibiting immune stress and complement activation.
6.Design of intelligent horizontal rotating cell culture device
Li-Fei YANG ; Ye-Rong QIAN ; Jun-Xi XIANG ; Ai-Hua SHI ; Xin LIU ; Sha-Sha WEI ; Yi LYU ; Peng LIU
Chinese Medical Equipment Journal 2024;45(9):41-45
Objective To develop an intelligent horizontal rotating cell culture device with high modularity,easy operation,easy disinfection,low cost and high stability.Methods The cell culture device consisted of a rotating culture module,a dirve module,a control module and control software,with the shells of all the modules being manufactured by 3D printing.The rotating culture module was composed of a tubular electrospun scaffold,a cell culture chamber,a magnetic coupling rotor and polypropylene pipeline;the drive module was made up of a N20 reduction motor and a magnetic coupling rotor;the control module included an ESP-8266 chip and a printed circuit board;the control software was developed with Blinker IoT platform and C++language.The device was used to culture human intrahepatic bile duct epithelial cells to verify its effects.Results Light microscopy and scanning electron microscopy images showed that a uniform and continuous cell layer was formed on the surface of the tubular electrospun scaffold.Conclusion The intelligent horizontal rotating cell culture device achieves uniform growth of cells on the inner surface of tubular electrospun scaffolds,and can be used as an effective platform for cell culture on tubular scaffolds.[Chinese Medical Equipment Journal,2024,45(9):41-45]
7.Observation of the efficacy of Vonoprazan dual therapy in the eradication of Helicobacter pylori
Shi-Ling WANG ; Dan-Ni CHEN ; Zhao LIU ; Zhao-Li MA ; Qiang LI ; Hong LU ; Min LIU ; Xi GOU ; Jun WANG ; Xiao-Chuang SHU ; Qian REN
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(3):265-269
Objective This paper intends to compare the efficacy and safety of high-dose dual regimens containing Vonoprazan and proton pump inhibitor in patients infected with Helicobacter pylori(H.pylori).Methods A prospective randomized controlled study was conducted.According to inclusion and exclusion criteria.,243 patients with H.pylori infection admitted to the Department of Gastroenterology,the First Hospital of Lanzhou University from February 2023 to December 2023 were enrolled as the research objects.They were randomly divided into two groups.The high-dose dual therapy containing Vonoprazan group(VPZ-HDDT group)was given Vonoprazan fumarate tablet 20mg twice daily plus amoxicillin 750 mg four times daily for 14 days and the high-dose combination group containing PPI(PPI-HDDT group)was given esomeprazole 40 mg twice daily plus amoxicillin 750 mg four times daily for 14 days.Patients were followed up and recorded by telephone or WeChat on the 7th and 14th day of starting treatment for drug intake and occurrence of adverse reactions.Patients were instructed to recheck the 13C or 14C urea breath test at least 1 month after the end of medication.Treatment by protocol(PP)analysis,modified intention to treat(mITT)and intention-to-treat(ITT)analysis were used for H.pylori eradication rates in both groups,and compliance and incidence of adverse reactions were compared between the two groups.Results The eradication rates of the VPZ-HDDT group and the PPI-HDDT group in the initial treatment were 94.0%and 88.5%(P=0.209)by PP analysis,and 91.8%and 87.5%(P=0.358)86.7%by mITT analysis,and 81.9%(P=0.377)by ITT analysis,respectively.In the retreated patients,the PP analysis and mITT analysis eradication rates in these two groups were consistent,87.0%and 84.2%(P=0.800),respectively,and 83.3%and 76.2%(P=0.550)by ITT analysis.For the refractory H.pylori patients,the PP analysis and mITT analysis eradication rates in these two groups were also consistent,71.4%and 50.0%(P=0.429),and the eradication rates of ITT analysis were 62.5%and 50.0%(P=0.640),respectively.In different stratifications,the eradication rates of the VPZ-HDDT group were higher than those of the PPI-HDDT group,but the differences were not statistically significant.The incidence of adverse reactions and compliance of the VPZ-HDDT group and the PPI-HDDT group were similar,with no statistically significant differences.Conclusion Both two combination regimens can achieve clinically acceptable eradication rates(>85%)in the first-time treatment patients.For the retreated and refractory patients,the choice of vonoprazan is more beneficial.
8.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
9.Correlation between preoperative coronary angiography and postoperative acute kidney injury in cardiac surgery: A retrospective study in a single center
Changying ZHAO ; Yang YAN ; Tao SHI ; Yongxin LI ; Jing LI ; Wenyan LIU ; Miaomiao LIU ; Xinglong ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1820-1825
Objective To explore the relationship between preoperative coronary angiography and postoperative acute kidney injury (AKI) in cardiac surgery. Methods The clinical data of patients who underwent coronary angiography within 30 days before cardiac surgery in the First Affiliated Hospital of Xi’an Jiaotong University from January 2015 to April 2019 were retrospectively analyzed. Univariate analysis and multivariate logistic regression analyses were used to explore the relationship between the interval from preoperative coronary angiography to cardiac surgery and postoperative AKI. Results Finally 1 112 patients were collected, including 700 males and 412 females, with a median age of 61 (55, 66) years. The incidence of postoperative AKI was 40.8% (454/1 112), of which grade 2-3 AKI accounted for 11.9%. Multivariate analysis showed that age (OR=1.049, 95%CI 1.022-1.077, P<0.001), body mass index (OR=1.065, 95%CI 1.010-1.123, P=0.020) and time interval between preoperative coronary angiography and cardiac surgery within 24 hours (OR=1.625, 95%CI 1.116-2.364, P=0.011) were independent predictors of postoperative AKI. Patients who underwent coronary angiography within 24 hours before surgery had a 10.6% higher incidence of postoperative AKI compared to those who underwent angiography ≥24 hours before surgery (P=0.004). Patients who underwent valve surgery with or without coronary artery bypass grafting (CABG) had a higher risk of AKI than those who only underwent CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing coronary angiography within 24 hours before cardiac surgery did not prolong the length of ICU stay or hospital stay, nor did it increase the risk of death or renal failure after the operation. Conclusion Undergoing coronary angiography within 24 hours before cardiac surgery increases the risk of postoperative AKI.
10.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

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