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.

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 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.

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.

Responses to sedatives, analgesics and muscle relaxants vary among patients under general anesthesia, which could be ascribed to the disparities of clinical characteristics and genetic factors of individuals. Accumulating researches have indicated that gene polymorphisms of the receptors, transporters and metabolizing enzymes associated with anesthetics play a considerable role in their efficacy. However, a systematically summarized study on the mechanisms of gene polymorphisms on pharmacodynamics and pharmacokinetics of anesthetics is still lacking. In this paper, the recent researches on pharmacogenomics of sedatives, analgesics and muscle relaxants are comprehensively reviewed, and the contributions and mechanisms of polymorphisms to the differences of individual efficacy of these drugs are discussed, so as to provide guidance for the formulation of a rational anesthesia regimen for patients with various genotypes.

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.

Objective To evaluate the effect of thoracoscope assisted intercostal nerve block combined with nalbuphine for postoperative multimodal analgesia after lung segment resection surgery.Methods From April 2022 to September 2022,60 patients scheduled for thoracoscopic lung segment resection surgery were selected and divided into two groups according to the random number table,with 30 patients in each group.The patients in the observation group received intercostal nerve block under thoracoscope before closing the chest,and the postoperative analgesia pump was Naborphine combined with sufentanil for patient-controlled intravenous analgesia;In the control group,the thoracic cavity was closed directly,and sufentanil was used for patient-controlled intravenous analgesia.The visual analog pain score(V AS),the number of PCI A effective pressing,the situation of rescue analgesia and the occurrence of related adverse reactions were recorded 2 h,4 h,8 h,24 h and 48 h after surgery.Results The VAS scores at rest of the observation group at2h,4h,8h,24h and 48 h after operation 1.8±0.8,1.9±0.8,2.1±0.9,2.3±0.9,2.1±0.8,compared with control group 3.3±1.1,3.5±1.0,2.8±0.9,2.7± 0.7,2.6±0.8 were all significantly lower(P＜0.05).The VAS scores during activity of the observation group at 2 h,4 h,and 8 h after operation 2.2±0.6,2.3±0.6,2.5±0.9,compared with control group 3.9±1.9、3.9±1.7、3.3±1.7 were significantly lower(P＜0.05).The effective press times of PCIA in the observation group within 24 hours and 48 hours after operation were 2.7±1.5 and 5.4±2.3 times,while those in the control group were 5.2±3.4 and 10.2±6.0 times.The difference between the two groups was statistically significant(P＜0.05).The number of patients in the observation group receiving postoperative analgesia was less than that in the control group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).The satisfaction rate of patients in the observation group was higher than that in the control group,with a statistically significant difference(P＜0.05).Conclusion Thoracoscope assisted intercostal nerve block combined with nalbuphine can be a good choice for postoperative multimodal analgesia in lung segment resection surgery.

【Objective】 To compare the perioperative blood loss between interlaminar and transforaminal approaches by percutaneous endoscopic discectomy in order to provide more reference for guiding the proper choice of surgical methods clinically. 【Methods】 We retrospectively analyzed the clinical data of 160 patients who underwent percutaneous endoscopic lumbar discectomy from June 2019 to November 2020， with 80 patients in interlaminar approach group and 80 in transforaminal approach group. The blood loss was calculated according to Gross formula. 【Results】 The perioperative total blood loss （mL）， hidden blood loss （mL） and hemoglobin loss （g/L） were significantly lower in interlaminar approach group than in transforaminal approach group （119.73±179.26 vs. 158.6±190.65， 109.73±179.53 vs. 148.78±190.19， 3.76±8.12 vs. 4.31±7.62） （P<0.05）. However， there was no significant difference in visible blood loss between the two groups. 【Conclusion】 The perioperative hidden blood loss accounts for a large proportion in percutaneous endoscopic lumbar discectomy. In addition， the interlaminar approach causes less blood loss than the transforaminal approach.

Objective:To investigate the clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio (NLR) in patients with multiple myeloma (MM).Methods:The clinical data of 124 MM patients in the Third Affiliated Hospital of Soochow University from December 2002 to April 2017 were retrospectively analyzed, and 31 healthy people were chosen as the controls. Peripheral blood T lymphocyte subsets were detected by using flow cytometry, and the correlations between CD4/CD8 ration and related clinical indicators were also investigated. All MM patients were divided into the high NLR group and the low NLR group according to the media of NLR, and the correlation of them with related clinical indicators, chromosome karyotype, overall survival (OS) and progression-free survival (PFS) was also compared.Results:Compared with the healthy control group, the proportion of CD4 + T cells [(35.28±6.58)% vs. (31.85±6.76)%, t = -2.067, P = 0.043], absolute value of NK cells [0.22×10 9/L (0.13×10 9/L-0.59×10 9/L) vs. 0.17×10 9/L (0.00×10 9/L-0.42×10 9/L), Z = -2.614, P = 0.009] and CD4/CD8 ratio [0.97 (0.50-2.69) vs. 0.81 (0.30-1.28), Z = -2.253, P = 0.024] was decreased, respectively. The proportion of CD8 + cells was increased [(36.93±7.38)% vs. (40.50±6.50)%, t = 2.074, P = 0.042] in MM group. The hemoglobin level of CD4/CD8 ratio ≥0.94 group was higher than that of CD4/CD8 ratio <0.94 [(98.89±21.35) g/L vs.(80.60±23.23) g/L, t = -2.066, P = 0.047]. Compared with the healthy control group, NLR was increased in MM group [1.54 (1.10-3.23) vs. 1.95 (0.29-12.70), Z = -2.384, P = 0.017]. Compared with the low NLR group (<1.95), serum β 2-microglobulin [4.56 mg/L (1.63-12.60 mg/L) vs. 6.17 mg/L (1.58-67.50 mg/L), Z = -2.586, P = 0.010] and serum creatinine [84.5 μmol/L (43.0-376.5 μmol/L) vs. 113.0 μmol/L (46.5-754.0 μmol/L), Z = -3.866, P < 0.001] was increased in the high NLR group for MM patients. The proportion of the male patients, β 2-microglobulin > 5.5 mg/L, serum creatinine > 177 μmol/L, stage Ⅲ of international staging system (ISS) in the high NLR group was higher than that in the low NLR group (all P < 0.05), and there was no statistically significant difference in the composition of chromosome karyotype (all P > 0.05). The median OS time in the low NLR group was longer than that in the high NLR group [30 months (20-40 months) vs. 17 months (7-27 months), χ 2 = 4.519, P = 0.034], and there was no statistically significant difference in the PFS of both groups ( P > 0.05). Multivariate Cox analysis demonstrated that the age, corrected serum calcium, serum creatinine, lactic dehydrogenase were the independent influencing factors of OS in MM (all P < 0.05), while NLR wasn′t an independent influencing factor of OS in MM ( P = 0.513). Conclusions:CD4/CD8 ratio is decreased and immune dysfunction occurs in MM patients. MM patients with high NLR have a shorter OS time.

Cognitive impairment is one of the three primary symptoms of schizophrenic patients and shows important value in early detection and warning for high-risk individuals. To study the specifics of electroencephalogram (EEG) in patients with schizophrenia under the cognitive load, we collected EEG signals from 17 schizophrenic patients and 19 healthy controls, extracted signals of each band based on wavelet transform, calculated the characteristics of nonlinear dynamic and functional brain networks, and automatically classified the two groups of people by using a machine learning algorithm. Experimental results indicated that the correlation dimension and sample entropy showed significant differences in α, β, θ, and γ rhythm of the Fp1 and Fp2 electrodes between groups under the cognitive load. These results implied that the functional disruptions in the frontal lobe might be the important factors of cognitive impairments in schizophrenic patients. Further results of the automatic classification analysis indicated that the combination of nonlinear dynamics and functional brain network properties as the input characteristics of the classifier showed the best performance, with the accuracy of 76.77%, sensitivity of 72.09%, and specificity of 80.36%. The results of this study demonstrated that the combination of nonlinear dynamics and function brain network properties may be potential biomarkers for early screening and auxiliary diagnosis of schizophrenia.