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.

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.

Diabetic retinopathy(DR)is a common ocular chronic microvascular complication of diabetes mellitus and is the leading blinding fundus disease in people over 40 years of age.Current studies have shown that neuroglial vascular u-nit(NGVU)injury causes a variety of characteristic fundus changes in DR patients,including exudation,cotton wool spots,microangioma,bleeding,and neovascularization.Recent studies have confirmed that retinal NGVU injury in DR pa-tients occurs before retinal microangiopathy and is closely related to impaired visual function,so NGVU is expected to be a potential therapeutic target for the prevention and treatment of early DR in the future.In this paper,the research progress on the relationship between NGVU and DR treatment is reviewed,intending to provide new research directions for the pre-vention and intervention of early DR progression.

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.

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.

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.

[Abstract] Objective: To construct and verify the anti-tumor activity of chimeric antigen receptor (CAR) modified NK-92 cells (CAR-NK-92 cells) targeting prostate stem cell antigen (PSCA) in cervical cancer. Methods: Lentiviral vector expressing CAR targeting PSCA was constructed, and PSCA CAR-NK-92 cells were obtained by lentivirus transfection. The expression of PSCA in human cervical cancer cells was determined by Flow cytometry and Western blotting. The killing effect of PSCA CAR-NK-92 cells against cervical cancer cells was verified by co-incubation of effector and target cells in vitro, and the tumor inhibitory ability of PSCA CAR-NK-92 cells was verified with the nude mice xenograft model in vivo. Results: PSCA CAR-NK-92 cells were successfully constructed. PSCA was highly expressed in human cervical cancer Hela and MS751 cells (all P<0.01). In vitro co-incubation results showed that PSCA CAR-NK-92 cells could lyse PSCA+ cervical cancer transplanted tumor in a dose-dependent manner. In vivo anti-tumor data showed that PSCA CAR-NK-92 cells significantly inhibited the growth of cervical cancer cells compared with NK-92 cells transfected with vehicle vectors (P<0.01). In addition, PSCA CAR-NK-92 cells could effectively infiltrate tumor tissues and promote the secretion of anti-tumor cytokines TNF-α and IFN-γ (all P<0.01). Conclusion: The CAR-NK-92 targeting PSCA shows good anti-tumor effect on PSCA+ tumor cells both in vitro and in vivo, and has potential to be a therapeutic strategy for cervical cancer.

Objective To investigate the relationship between prothrombin fragment 1+2 (F1+2) and peripherally inserted central catheter (PICC) associated thrombosis in cervical cancer patients, and provide certain clinical basis of early prevention in peripherally inserted central catheter associated thrombosis in cervical cancer patients. Methods One hundred and forty cervical patients with PICC were enrolled in this study, and they were divided into thrombosis group (35 patients) and non-thrombosis group (105 patients). The level of F1+2 was examined using enzyme-linked immunoassay, and was analyzed according to the clinic features. Results The level of F1+2 was correlated with clinical stage (r = 0.640, P = 0.004);but was not correlated with age, type of tumor and concurrent radiochemotherapy (P>0.05). The level of F1+2 in thrombosis group was (520.343 ± 121.759) pmol/L, in non- thrombosis group was (388.361 ± 104.873) pmol/L, and there was significant difference (P =0.001). The multi-factors Logistic analysis showed that the level of F1+2 (OR=1.011, P=0.001) and age (OR = 21.025, P = 0.031) were independent risk factors for the PICC associated with thrombosis in cervical cancer. Conclusions The level of F1+2 is closely related with clinical stage and PICC associated thrombosis, and it is an independent risk factor for the PICC associated with thrombosis in cervical cancer.

Objective To investigate the application value of extracorporeal extended field radiotherapy in locally advanced cervical cancer. Methods A total of one hundred and twenty patients with stage IIB?IVA cervical cancer in the First Affiliated Hospital of Hebei North University from June 2012 to June 2014 were randomly divided into two groups:the control group and the observation group,each with 60 cases. The routine concurrent chemoradiotherapy was adopted in the control group. The observation group was treated with extracorporeal extended field radiotherapy combined with concurrent chemotherapy. The patients have been followed up for three years. The total efficacy rate,toxicity reaction,local progression free survival time ( PFS) and survival rate of the two groups were compared. Results The total efficacy rate in the observation group was significantly higher than that of the control group ( 88. 3%( 53/60 ) vs. 73. 3%( 44/60 ) , χ2 = 4. 357, P=0. 037),while the incidences of toxicity reaction in the two groups were 18. 3%(11/60) and 16. 7%(10/60), the difference was not statistically significant (χ2=0. 058,P=0. 810) ,the percentages of I and II degree in the two groups were 3. 4%( 2/60 ) and 3. 4%( 2/60 ) , the difference between the two groups was not statistically significant (Z=0. 000,P=1. 000). The PFS value in the observation group was significantly longer than that of the control group ( 25. 6 months vs. 13. 8 months,χ2 = 25. 624, P= 0. 000 ) , and the survival rate in the observation group improved significantly ( 53. 3%( 32/60 ) vs. 33. 3%( 20/60 ) , the difference was statistically significant (χ2 = 4. 887, P= 0. 027 ) . Conclusion Extracorporeal extended field radiotherapy is safe and effective in the treatment of locally advanced cervical cancer.

Objective To explore the feasibility and value of preservation of left colonic artery (LCA) in dealing with inferior mesenteric artery (IMA) in laparoscopic anterior resection of rectal carcinoma.Methods The clinical data of 72 cases of laparoscopic anterior resection of rectal carcinoma from April 2010 to October 2013 were retrospectively analyzed including 32 cases with preservation of LCA (observation group) and 40 cases without preservation of LCA (control group).The blood loss,operative time,postoperative exhaust time,terminal ileum stoma,the number of lymph nodes removed around the root of IMA,the rate of lymph node metastasis around the root of IMA and prognosis were compared between two groups.Results There was no significant difference in the blood loss,operative time,postoperative exhaust time,terminal ileum stoma,the number of lymph nodes removed around the root of IMA,the rate of lymph node metastasis around the root of IMA between two groups (P ＞ 0.05).No case in observation group needed to free the splenic flexure of colon and to make the terminal ileum stoma,while 3 cases in control group needed to free splenic flexure of colon because of blood supply disorder in the proximal intestine (P =0.046),and 4 cases underwent terminal ileum stoma following anastomosis (P =0.042).No anastomotic leakage occurred in observation group,while 2 cases of anastomotic leakage occurred in control group(P =0.090).After followed up for 6-48 months,no significant difference was found in local recurrence and liver metastasis in two groups (P ＞ 0.05).Conclusion Laparoscopic anterior resection of rectal carcinoma with preservation of LCA in dealing with IMA can effectively retain the blood supply of proximal intestine.