Objective To investigate the role of low dose esketamine in pretreated limb ischemia-reperfusion inju-ry.Methods The rats were divided into sham-operated group(Sham group),ischemia-reperfusion group(I/R group,3 h of ischemia and 2 h of reperfusion),esketamine group(ESK group,ip,5 mg/kg).The plasma con-centrations of creatine kinase(CK)and lactate dehydrogenase(LDH)were measured.The wet/dry weight ratio of skeletal muscle was immediately detected.The gastrocnemius muscle was harvested and the level of malondial-dehyde(MDA)and superoxide dismutase(SOD)was detected by colorimetric assay.The expression of nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)were detected by Western blot and im-munohistochemical staining.Results Compared with Sham group,the index of wet/dry weight ratio,MDA,CK,LDH,Nrf2 and HO-1 were all increased,but SOD was decreased in I/R group(P＜0.05).Compared with I/R group,the index of wet/dry weight ratio,MDA,CK and LDH were significantly lower,but SOD and Nrf2 and HO-1 were significantly higher in ESK group(P＜0.05).Conclusions ESK may increase Nrf2 in the nucleus,thereby increase the HO-1 protein as an antioxidant agent.

Objective:To evaluate the efficacy and safety of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) monotherapy for brain metastasis in advanced non-small cell lung cancer (NSCLC), and to explore the timing of immunomonotherapy and the application of hormone on the efficacy of ICI.Methods:By searching literature in CNKI, Wanfang, VIP, PubMed, CBM, Embase, Cochrane Library and Web of Science databases, the advanced NSCLC patients with brain metastasis who received ICI treatment were identified, including patients with symptomatic brain metastasis who had received hormone therapy or brain surgery or radiotherapy. Meta-analysis was performed on the collected data to evaluate the systemic objective response rate (sORR) and intracerebral tumor objective response rate (iORR), the iORR of whether ICI monotherapy was first-line therapy, and the iORR of whether hormone was used were evaluated, and the incidence of adverse reactions was evaluated.Results:Fifteen studies were finally included, with a total of 4 033 patients, including 917 patients with brain metastasis. The iORR of immunomonotherapy was 26% (95% CI 19%-34%) and the sORR was 28% (95% CI 18%-40%). The iORR of first-line immunomonotherapy was 49% (95% CI 39%-58%). The iORR of symptomatic patients with hormone therapy and asymptomatic patients without hormone therapy was 26% (95% CI 20%-33%) and 19% (95% CI 16%-22%), respectively. The overall incidence of grade 3-4 adverse reactions was 14% (95% CI 11%-17%). Conclusions:The efficacy of ICI monotherapy in the first-line treatment of PD-L1-positive NSCLC patients with brain metastasis is better than that in the subsequent line therapy, and the application of hormone does not affect the efficacy of ICI. ICI monotherapy in the treatment of advanced NSCLC patients with brain metastasis is safe.

Objective:To investigate the influence of Jinshuibao tablet on immune function, therapeutic efficacy and safety in treatment of advanced lung squamous cell carcinoma patients treated by chemotherapy.Methods:The clinical data of 124 patients with stage Ⅳ lung squamous cell carcinoma who were admitted to Shanxi Provincial Cancer Hospital from January 2015 to December 2017 were retrospectively analyzed, including 60 patients treated by Jinshuibao tablet combined with chemotherapy (the observation group) and 64 patients treated by chemotherapy alone (the control group). The changes of immune function, therapeutic effect, and side effects were compared between the two groups.Results:The percentage of CD4 + cells after treatment [(33.4±8.9)% vs. (45.5±11.8)%, t = 2.71, P < 0.05] and CD4 +/CD8 + (0.9±0.3 vs. 1.5±0.4, t = 3.31, P < 0.05) in the observation group was increased compared with that before treatment, CD8 + cells was decreased compared with that before treatment [(30.9±8.6)% vs. (21.1±8.1)%, t = 2.42, P < 0.05], interferon-γ (IFN-γ) [(7.7±2.8)% vs. (14.1±2.4)%, t = 2.74, P < 0.05] and interleukin-2 (IL-2) [(8.8±3.2)% vs. (12.7±1.6)%, t = 2.96, P < 0.05] was increased compared with that before treatment. The percentage of CD3 + cells [(57.9±8.2)% vs. (45.2±10.8)%, t = 2.70, P < 0.05], CD4 + cells [(32.9±9.0)% vs. (22.8±9.6)%, t = 3.19, P < 0.05], NK cells [(14.9±3.1)% vs. (9.3±1.4)%, t = 2.97, P < 0.05] in the control group was decreased compared with that before treatment. Tumor necrosis factor α (TNF-α) was decreased compared with that before treatment [(6.8±1.4)% vs. (4.3±0.5)%, t = 3.23, P < 0.05]. There was a statistically significant difference in the level of T-cell subsets of both groups after treatment (all P <0.05); and the level of CD3 +, CD4 +, CD4 +/CD8 +, NK cells in the observation group was higher than that in the control group; CD8 + cell in the observation group was lower than that in the control group. There was no statistical difference in the level of IFN-γ, IL-2, TNF-α of both groups before treatment (all P > 0.05); the level of IFN-γ, IL-2, TNF-α in the observation group was higher than that in the control group after treatment, and the difference was statistically significant of both groups (all P < 0.05). The total effective rate of the observation group was higher than that in the control group, and the difference was statistically significant [31.3% (20/64) vs. 48.3% (29/60), χ 2 = 4.538, P = 0.033]; and the disease control rate in the observation group was higher than that in the control [56.3% (36/64) vs. 71.7% (43/60), χ 2 = 5.276, P = 0.022]. There was no significant difference between the two groups in adverse reactions of chemotherapy (all P > 0.05). Conclusion:Jinshuibao tablet combined with chemotherapy can improve the immune function and the efficacy of chemotherapy for patients with advanced lung squamous cell carcinoma.

Objective:To explore the quality of life of patients with advanced lung cancer and its influencing factors.Methods:A total of 220 patients with advanced lung cancer in Shanxi Provincial Cancer Hospital from June 2017 to June 2019 were selected. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and Quality and Life Questionnaire of Lung Cancer (QLQ-LC13) were used to evaluate the quality of life of patients. Combined with the clinicopathological data of the patients, multiple linear regression method was used to analyze the factors affecting the quality of life of patients with advanced lung cancer.Results:A total of 220 questionnaires were issued, and 184 (83.6%) valid questionnaires were returned. There were 102 cases (55.4%) of male and 82 cases (44.6%) of female. Among the 5 functional areas of QLQ-C30, the score of social function was low [(60.2±11.8) points], and the score of cognitive function was high [(78.5±13.4) points]; among the 3 symptom areas, the score of pain was high [(36.8±10.3) points]; among the 6 single items, the lack of appetite was more serious [(58.5±10.5) points]. Among the 10 symptom areas of QLQ-LC13, shortness of breath and cough were more prominent [(34.6±9.5) points and (33.6±6.8) points]. The quality of life of female patients, patients with older age, patients with fewer children, patients with more organ metastases, patients with other diseases and patients with chemotherapy was poor (all P < 0.05), while there was no correlation between smoking status, occupation and education level and the quality of life of advanced lung cancer patients (all P > 0.05). Conclusions:The quality of life of advanced lung cancer patients is closely related to gender, age, the number of children, the number of metastatic organs, with or without diseases and treatment methods. Targeted intervention measures are helpful to improve the quality of life of patients.

Objective To investigate the value of platelet-to-lymphocyte ratio (PLR) and cell proliferation antigen Ki-67 in judging the chemotherapy efficacy and prognosis of patients with advanced non-small cell lung cancer (NSCLC). Methods The clinical data of 132 patients with advanced NSCLC diagnosed by pathology and immunohistochemistry from January 2015 to January 2016 in Shanxi Provincial Cancer Hospital were retrospectively analyzed. Peripheral venous blood cells were collected before chemotherapy, the platelet and lymphocyte counts were detected by using blood cell analyzer to calculate PLR. Immunohistochemical SP method was used to detect the expression of Ki-67 in tissue sections. The platinum-containing dual-drug regimen was used in the first-line chemotherapy for at least 4 cycles. The χ2 test was used to compare the count data, and the logistic regression model was used to analyze the factors affecting the effective rate. The Kaplan-Meier method and log-rank test were used for survival analysis, and the Cox proportional hazards regression model was used for multivariate analysis of prognosis. Results The total effective rate of the first-line chemotherapy was 41.7％ (55/132). The 1-year and 2-year overall survival (OS) rates were 26.1％ and10.4％, respectively. and the mean progression-free survival (PFS) time was 5.7 months (95％ CI 3.2-10.9 months) and the median OS time was 14.05 months (95％ CI 6.8-18.4 months). The median PLR was 172.0. The effective rate in PLR < 172.0 group was higher than that in PLR≥172.0 group [60.6％ (40/66) vs. 22.7％(15/66), χ 2 = 19.481, P < 0.05], and the median OS time in PLR < 172.0 group was longer than that in PLR≥172.0 group (17.6 months vs. 15.0 months, χ 2 = 4.976, P < 0.05), and there was no significant difference in the median PFS time between the two groups (8.6 months vs. 6.5 months, χ 2 = 0.078, P > 0.05). There was no significant difference in the effective rate between Ki-67 negative group and positive group [40.0％ (28/70) vs. 43.5％ (27/62), χ 2 = 0.170, P > 0.05]. The median PFS time and OS time in Ki-67 negative group were longer than those in positive group (7.6 months vs. 6.5 months, χ 2 = 7.170, P < 0.05; 18.3 months vs. 14.5 months,χ 2 = 15.870, P < 0.05). According to the results of multivariate analysis, PLR was an effective independent factor for effective rate (P < 0.05), Ki-67 was an independent influencing factor for PFS (P < 0.05), and PLR and Ki-67 were independent influencing factors for OS (P < 0.05). Conclusion PLR and Ki-67 can be used as meaningful indicators for predicting the chemotherapy efficacy and prognosis of advanced NSCLC.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.
Acute Disease ; Animals ; Brain ; diagnostic imaging ; metabolism ; Brain Mapping ; Disease Models, Animal ; Fluorodeoxyglucose F18 ; Glucose ; metabolism ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; metabolism ; Male ; Neural Pathways ; diagnostic imaging ; metabolism ; Positron-Emission Tomography ; Radiopharmaceuticals ; Random Allocation ; Rats, Sprague-Dawley

Positron emission tomography (PET) imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by < 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensitivity and accuracy for stroke studies.
Animals ; Computer Simulation ; Disease Models, Animal ; Female ; Fluorodeoxyglucose F18 ; Image Processing, Computer-Assisted ; methods ; Infarction, Middle Cerebral Artery ; diagnostic imaging ; Male ; Positron-Emission Tomography ; methods ; Rats ; Rats, Sprague-Dawley ; Stroke ; diagnostic imaging

Objective: To investigate the risk factors of ventricular arrhythmias in patients with Brugada syndrome. Methods: Clinical data of 60 Brugada syndrome patients admitted in the department of cardiology of the First Affiliated Hospital of Nanjing Medical University from March 2003 to December 2016 were collected and retrospectively analyzed. The age at diagnosis was (43.2±13.1) years (0.6-83.0 years), 98.3% were males (n=59), and the patients were followed up to (92±41) months (12-169 months). The 12-lead surface electrocardiogram (ECG) recorded at the time of diagnosis and showing the highest type 1 ST elevation, either spontaneously or after provocative drug test, was used for the analysis. Patients were divided into ventricular arrhythmia (VA, n=12) group and non-ventricular arrhythmia (non-VA, n=48) group depending on the presence or absence of clinical VA event. The demographic data and ECG data of the 2 groups were compared, and the independent risk factors of VA events were analyzed by stepwise logistic regression. Results: Incidence of family history of sudden death (7/12 vs. 22.9% (11/48)) and percentage of type 1 ST elevation in the peripheral ECG leads (6/12 vs. 16.67% (8/48)) were significantly higher in VA group than in non-VA group (both P<0.05). Max Tpeak-Tend (Max-Tpe) interval ((144±53)ms vs. (110±16)ms) and dispersion of Tpe ((74±50)ms vs. (43±17)ms) were significantly higher in VA group than in non-VA group (both P<0.05). The area under receiver operating characteristic (ROC) curves for the Max-Tpe interval was 0.693 and Max-Tpe interval ≥140 ms was determined as an optimized cutoff point with increased risk of VA event, which had a sensitivity of 50.0%, a specificity of 98.0%, a positive predictive value of 85.7%, and a negative predictive value of 88.7% for predicting VA event. The ROC curves for the dispersion of Tpe was 0.775 and dispersion of Tpe ≥45 ms was determined as an optimized cutoff point for predicting VA event, which had a sensitivity of 91.7%, a specificity of 64.6%, a positive predictive value of 39.3%, and a negative predictive value of 96.9% for predicting VA event. In multivariate analysis, Max-Tpe interval ≥140 ms (OR=27.53, 95%CI 1.07-706.77, P=0.045) and family history of sudden death (OR=24.63, 95%CI 2.05-295.38, P=0.011) were found to be the independent risk factors of arrhythmic events. Conclusions Max-Tpe interval ≥140 ms and family history of sudden death are risk factors of VA event in included patients with Brugada syndrome.

Purpose To explore the role of posterior cingulate cortex (PCC) dysfunction in the pathogenesis of depression and its relationship with the clinical features of depression by analyzing the effective connection among the inner areas of PCC of patients in depression.Materials and Methods The spectral dynamic causal model (spDCM) was used to analyze the resting state functional magnetic resonance imaging (fMRI) data from the PCC inner areas Brodmann area (BA) 23,BA29,BA30,BA31 in the major depressive disorder group (MDD,n=23) and healthy control group (HC,n=36).Results Compared with HC group,the strength of BA30 self-connection of MDD group existed significant difference (t=2.53,P＜0.05).In MDD group,the connection of BA23 toward BA31 had abnormal activation,and the abnormal inhibition occurred in BA23 toward BA30;compared with HC group and after a＜0.05 Hz correction,there were significant differences in the bi-directional connections for BA23 and BA31,BA39 and BA31,BA30 and BA31,and in the unidirectional connections for BA23 to BA31,BA30 to BA23,BA30 to BA29 in MDD group.Conelusion The effective connection and connective nodes and edges in the inner areas of PCC in the depression disorder patients were abnormal.

Objective To investigate the significance of resistant gene detection combined with adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in the second-line chemotherapy of lung squamous cell cancer, and to provide a reference for clinical treatment. Methods 150 patients with lung squamous cell cancer diagnosed by histopathology or cytology and with the disease progressed after NP regime chemotherapy were enrolled. The mRNA expressions of excision repair cross complementation 1 (ERCC1) and ribonucleotide reductase M1 (RRM1) were detected by RT-PCR, and ATP-TCA was carried out. After detected by RT-PCR and ATP-TCA, the patients who were sensitive to gemcitabine plus cisplatin (GP) accepted the second-line systemic chemotherapy with GP regimen, and the others who were not sensitive to GP regimen or whose results of gene detection and ATP-TCA were on the contrary took the second-line chemotherapy regimens with docetaxel plus cisplatin (DP). Both groups accepted 2-4 cycles of systemic chemotherapy. The chest CT was followed up, and the response rate (RR), progression-free survival (PFS) and median survival time (MST) were investigated. Results The RR of GP group was 36.2 % (17/47), while the DP group was 28.1 % (26/92), and the difference was statistically significant (χ2= 4.274, P< 0.05). The media PFS of GP group and DP group were 4.2 months (95%CI 3.485-5.348 months) and 3.6 months (95 %CI 2.685-4.648 months), respectively, and the difference was statistically significant (P<0.05). The MST of GP group and DP group were 9.6 months (95 %CI 8.283-10.637 months) and 8.9 months (95 %CI 7.384-9.648 months), respectively, and there was no statistically significant difference (P> 0.05). Conclusion The resistance gene detection combined with ATP-TCA have certain guiding significance on the second-line chemotherapy for advanced lung squamous cell cancer.