1.LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway
Xirui FAN ; Zhilin QI ; Yuanjie DENG ; Zihan YANG ; Li SUN ; Guohao LI ; Juanjuan LIANG ; Fei WU ; Liwen YUAN
Journal of Southern Medical University 2024;44(10):2033-2043
Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.
2.LncRNA MAGI2-AS3 enhances cisplatin sensitivity of non-small cell lung cancer cells by regulating the miR-1269a/PTEN/AKT pathway
Xirui FAN ; Zhilin QI ; Yuanjie DENG ; Zihan YANG ; Li SUN ; Guohao LI ; Juanjuan LIANG ; Fei WU ; Liwen YUAN
Journal of Southern Medical University 2024;44(10):2033-2043
Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.
3.Inhibition of FoxO1 exerts a protective effect on diabetic cardiomyopathy rats by regulating JAK/STAT3 signaling pathway
Huilin LUO ; Zhilin WU ; Yunyun YANG
Chinese Journal of Diabetes 2024;32(9):689-694
Objective To investigate the impact of forkhead box O1(FoxO1)on oxidative stress andcardiomyocyte apoptosis in diabetic cardiomyopathy(DCM)rats through Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)pathway.Methods A total of 60 rats were divided into normal control group(NC),model group(Mod),FoxO1 agonist group(Res),FoxO1 inhibitor group(AS1842856)and FoxO1 inhibitor+AG490 group(AS1842856+AG490),with 12 rats in each group.DCM models were established in all groups except NC group.After successful modeling,they were given drugs,and the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-PX)were tested.HE and Masson staining were used to detect the pathological damage of myocardial tissue.TUNEL staining was used to observe myocardial apoptosis.Western blot was used to detect FoxO1,Bim,Bcl-2 related X protein(Bax),p-JAK1,p-JAK2,p-STAT3,JAK1,JAK2 and STAT3 proteins.Results Compared with NC group,the expressions of FBG,MDA,cardiomyocyte apoptosis rate,FoxO1 protein,Bax protein and Bim protein were increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 were increased in Mod group(P<0.05).Compared with Mod group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),while the expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 decreased in Res group(P<0.05).The expressions of HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT3/STAT3 increased(P<0.05),while FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein decreased in AS1842856 group(P<0.05).Compared with AS1842856 group,FBG,MDA,myocardial apoptosis rate,FoxO1 protein,Bax protein and Bim protein increased(P<0.05),and HR,LVEF,LVFS,GSH-PX,SOD,p-JAK1/JAK1,p-JAK2/JAK2,p-STAT3/STAT3 decreasedin AS1842856+AG490 group(P<0.05).Conclusions Inhibition of FoxO1 may exert a protective effect on DCM rats by activating the JAK2/STAT3 pathway.
4.Efficacy of low molecular weight heparin-assisted plasma exchange in the treatment of hyperlipidemic severe acute pancreatitis
Jun WANG ; Biwen YUAN ; Li YANG ; Zhilin CAO ; Xin HUANG
China Pharmacist 2024;28(10):245-251
Objective To investigate the clinical efficacy of low molecular weight heparin (LMWH)-assisted plasma exchange (PE) in the treatment of patients with hyperlipidemic severe acute pancreatitis (HLSAP).Methods Patients with HLSAP diagnosed and treated in Leshan People's Hospital were retrospectively selected from January 2023 to April 2024 and their clinical data were analyzed.According to the diagnosis and treatment plans,they were divided into the control group (PE) and the study group (LMWH-assisted PE).The coagulation function[fibrinogen (Fib),thrombin time (TT),activated partial thromboplastin time (APTT) and prothrombin time (PT)],plasma specific viscosity,lipid levels[total cholesterol (TC),triglyceride (TG)],inflammatory factors[white blood cell count (WBC),erythrocyte sedimentation rate (ESR),C reactive protein (CRP),amylase (AMY) and lipase (LYP)]were compared before and after treatment between the two groups.The duration of continuous renal replacement therapy (CRRT),length of hospitalization and incidence of new organ dysfunction were compared between the two groups.Results A total of 105 HLSAP patients were included in the study,with 50 in the control group and 55 in the study group.Before treatment,there was no statistically significant difference in coagulation function,lipid levels,plasma specific viscosity and inflammatory factors between the two groups (P>0.05).After treatment,Fib,TC,TG,plasma specific viscosity,WBC,ESR,CRP,AMY and LYP were significantly lower in the study group than in the control group (P<0.05),while TT,APTT and PT were significantly higher than in the control group (P<0.05).The duration of CRRT,hospitalization time and incidence of new organ dysfunction were lower in the study group than in the control group (P<0.05).In terms of adverse reactions,no transfusion adverse reactions and serious complications occurred in both groups during the treatment period.Conclusion LMWH-assisted PE has a better effect in the treatment of HLSAP,which can improve the coagulation function,blood lipid levels and inflammatory factors of HLSAP patients,shorten the hospital stay and the duration of CRRT,and reduce the incidence of new organ dysfunction.
5.Histopathological changes in secondary visual cortex and enhanced calcium activity in neurons being involved in microwave radiation-induced anxiety-like behavior
Zhihua FENG ; Ting PAN ; Ganghua HE ; Chenxu CHANG ; Zhilin CUI ; Meiying YANG ; Yanhui HAO ; Fengsong LIU ; Yang LI ; Hongyan ZUO
Chinese Journal of Radiological Medicine and Protection 2024;44(6):464-471
Objective:To clarify the effects of microwave radiation on anxiety-like behavior, the histomorphology of the secondary visual cortex, and calcium activity in neurons.Methods:36 C57BL/6N mice were selected and divided into control group and microwave radiation group according to the random number table method. In the simple behavioral testing, there were 8 mice in the control group and 7 mice in the radiation group. Combining fiber optic recording with behavioral experiments, there were 8 mice in the control group and 7 mice in the radiation group. Hematoxylin-eosin (HE) staining was conducted with 3 mice in each group. A high-power microwave simulated source in the X-band with a center frequency of 9.875 GHz and an average power density of 12 mW/cm 2 was used to irradiate the mice for 15 minutes, establishing a microwave radiation animal model. Then, anxiety-like behavior changes in the radiation group were identified using the open-field and elevated plus maze (EPM) tests. The effects of microwave radiation on the histomorphology of the secondary visual cortex were investigated using HE staining and optical microscopy. Based on the genetically encoded calcium imaging technique, as well as optical fiber recording combined with behavioral paradigms in the open field and the EPM, the changes of calcium activity in neurons in the V2M region of the secondary visual cortex were detected. Results:Compared to the control group, the radiation group showed a significant decrease in the frequency of exploring the central region of the open field and the open arm of the EPM ( t = 2.24, 3.10, P < 0.05). Furthermore, the radiation group exhibited the degeneration and apoptosis of some neurons in the secondary visual cortex, primarily manifested as pyknosis and deep staining, cell body shrinkage, and the slightly widening of perivascular space. Fiber optic recordings and behavioral experiments indicated that compared to the control group, mice in the radiation group exhibited significantly increased calcium activities in neurons of the secondary visual cortex when exploring the central region of the open field ( t = -2.75, P < 0.05) or the open arm of the EPM ( t = -2.77, -3.41, P < 0.05) compared to those before radiation after microwave exposure. Conclusions:Microwave radiation can induce anxiety-like behaviors and histopathological changes in the secondary visual cortex. Increased calcium activity in neurons of the secondary visual cortex is proved to be an important mechanism underlying the changes in anxiety-like behavior due to microwave radiation.
6.Analyzing and monitoring real-world clinical safety of ensartinib for the treatment of patients with ALK-positive non-small cell lung cancer
Xiaobin YUAN ; Yang WANG ; Min YANG ; Pengxiang WU ; Zhilin SHEN ; Yongbin MA ; Lieming DING
Journal of International Oncology 2023;50(3):150-156
Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.
7.Clinical study on modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding with failure of the spleen to control blood vessels syndrome
Wenbo LIU ; Yizhou WANG ; Shimin CHEN ; Hui YANG ; Yu HUANG ; Lingling YAN ; Zhilin ZHANG
International Journal of Traditional Chinese Medicine 2023;45(2):154-159
Objective:To investigate the clinical efficacy of modified Guipi Decoction combined with omeprazole in the treatment of acute non-variceal upper gastrointestinal bleeding (ANVUGIB) with failure of the spleen to control blood vessels syndrome.Methods:Prospective cohort study. A total of 120 patients from January 2018 to December 2021 Taihe County Hospital of Traditional Chinese Medicine with ANVUGIB of failure of the spleen to control blood vessels syndrome were selected, and the patients were divided into observation group and control group according to the random number table method, with 60 cases in each group. The control group was treated with a large dosage of proton pump inhibitor (omeprazole injection was injected intravenously first, and then omeprazole enteric coated tablets were taken); the observation group took Guipi Decoction on the basis of the control group, and both groups were treated for 7 days. TCM syndrome score, Hemoglobin (Hb) and hematocrit (HCT) levels were measured by colorimetry before and after the treatment. BUN was detected by urease glutamate dehydrogenase method. Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) levels were detected by immunoturbidimetry. The adverse reactions during treatment were recorded and the clinical efficacy was evaluated.Results:Two patients in the observation group and two patients in the control group dropped out of the study. After treatment, the scores of main symptoms, secondary symptoms and total scores in the observation group were lower than those in the control group ( t values were respectively 10.73, 4.45, 7.98, P<0.05). After treatment, the levels of HCT [(41.25 ± 5.03)% vs. (38.19 ± 5.26)%, t=2.95], Hb [(81.09 ± 5.23) g/L vs. (78.39 ± 5.37) g/L, t=2.74] in the observation group were higher than those in the control group ( P<0.01), and BUN [(4.38±0.96) mmol/L vs. (5.39 ± 1.13) mmol/L, t=5.19] was lower than that in the control group ( P<0.01); PT [(12.48 ± 0.67) s vs. (13.22 ± 0.73) s, t=5.69], APTT [(24.66 ± 2.29) s vs. (27.78 ± 2.04) s, t=7.75] were lower than those in the control group ( P<0.01), and FIB [(3.68 ± 0.62) g/L vs. (3.41 ± 0.74) g/L, t=2.13] level was higher than that in the control group ( P<0.05). The total effective rate of the observation group was 93.1% (54/58), and that of the control group was 79.3% (46/58), with statistical significance ( χ2=4.64, P=0.031). During the treatment, the incidence of adverse reactions in the control group was 3.4% (2/58), while that in the observation group was 1.7% (1/58), without statistical significance ( χ2=0.34, P=0.559). Conclusion:High-dosage omeprazole treatment with the addition of internal administration of Guipi Decoction can significantly improve coagulation function, correct the signs and symptoms associated with insufficient blood volume in the body circulation, improve hemostatic efficiency, and reduce the risk of bleeding in patients with ANVUGIB, without increasing the risk of patient safety with the drug.
8.Analysis on health-related quality of life of migrant workers with pneumoconiosis in Hunan Province
Zhilin YU ; Xiaoli LIU ; Dan YU ; Lehua YANG ; Xiongbin XIAO ; Zhongchun ZHAN ; Weirong DAI ; Li LI
China Occupational Medicine 2023;50(3):301-304
Objective To understand the health-related quality of life (HRQOL) of migrant workers with pneumoconiosis who received basic medical treatment in Hunan Province. Methods A total of 613 migrant workers with pneumoconiosis who received basic medical treatment and assistance in Hunan Province was selected as the study subjects using stratified random sampling method. The European Quality of Life-5 Dimensions (EQ-5D) questionnaire was used to assess their HRQOL. Results The abnormality of the five dimensions of the EQ-5D health description system, from high to low, were as follows: daily activities, mobility, pain/discomfort, anxiety/depression, and self-care, with the abnormal rates of 50.9%, 46.8%, 41.1%, 21.0%, and 14.5%, respectively. The visual analogue scale (VAS) score of EQ-5D was (63.5±18.6) points. Patients with stage Ⅲ pneumoconiosis had high abnormality in mobility, daily activities, and pain/discomfort compared with those with stage Ⅰ and Ⅱ disease (all P<0.02). Patients in stage Ⅱ and Ⅲ of pneumoconiosis had higher incidence of anxiety/depression compared with those with stage I disease (all P<0.02). Patients with complications in addition to pneumoconiosis had higher abnormality in mobility, self-care, and pain/discomfort compared to those with simple pneumoconiosis or those eligible for lung lavage treatment (all P<0.02). Patients with simple pneumoconiosis had a higher incidence of anxiety/depression compared with those eligible for lung lavage treatment (P<0.02). Patients with stage Ⅲ pneumoconiosis had lower average VAS scores compared with stage Ⅰ and Ⅱ patients (all P<0.02). Patients with simple pneumoconiosis or those with complications had lower average VAS scores compared with those eligible for lung lavage treatment (all P<0.05). Conclusion The HRQOL of pneumoconiosis patients among migrant workers needs improvement, especially for patients with stage Ⅲ disease and those with complications. This study indicates the need of optimizing policies, raising the hospitalization expense limit for critically ill patients with stage Ⅲ pneumoconiosis or with complications, and improving their HRQOL.
9.Kinesio taping methods for stroke survivors with shoulder-hand syndrome
Liang HUANG ; Huaan CAI ; Juan ZHANG ; Jinggui DENG ; Chan YI ; Jin LIU ; Lingling YANG ; Zhilin MA ; Wei LIU ; Xueqing TANG
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(11):994-998
Objective:To observe the effects of different kinesio taping methods on hand swelling, shoulder pain, upper limb motor function and ability in the activities of daily living of stroke survivors with shoulder-hand syndrome.Methods:Sixty stroke survivors with shoulder-hand syndrome were randomly divided into groups A, B, C and a control group, each of 15. In addition to routine rehabilitation training and drug treatment, as well as claw-shaped and I-shaped taping of the hand and wrist, group A received I-shaped kinesio taping, B received Y-shape and C received I-shape plus Y-shaped taping of the shoulder. Before and after 4 weeks, the drainage method was employed to calculate the difference in volume between the two hands. Their temperatures were also measured. The subjects reported shoulder pain using a visual analog scale (VAS). Upper limb motor functioning was quantified using Fugl-Meyer scores, and difficulties in the activities of daily living were evaluated using the modified Barthel index (MBI).Results:Before the treatment there were no significant differences among the four groups in terms of any of the measurements. Afterward the treatment, significant improvement was observed in the volume and temperature differences between hands, as well as in the VAS, FMA and MBI scores. After the treatment, group C′s average FMA score was significantly higher than those of the other groups. There was no significant difference in MBI scores among the four groups.Conclusions:Supplementing rehabilitation training with I-shaped plus Y-shaped kinesio taping can effectively reduce the volume and temperature differences between the hands, relieve shoulder pain, and improve effectiveness in the activities of daily living of persons with shoulder-hand syndrome after a stroke. Hand-claw and wrist-I taping also have some effect.
10.Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver by Remodeling the Liver Immune Microenvironment
Na YUAN ; Xiaoyan LI ; Meng WANG ; Zhilin ZHANG ; Lu QIAO ; Yamei GAO ; Xinjian XU ; Jie ZHI ; Yang LI ; Zhongxin LI ; Yitao JIA
Gut and Liver 2022;16(4):575-588
Background/Aims:
This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis.
Methods:
A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis.
Results:
Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration.
Conclusions
An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

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