Objective To explore the relationship between peripheral blood T lymphocyte subsets and prognosis of patients with advanced non-small cell lung cancer (NSCLC) who received treatment with camrelizumab. Methods We retrospectively collected data from 88 patients with advanced NSCLC who underwent camrelizumab treatment. Peripheral blood lymphocyte subsets were collected from patients before and two months after treatment. Kaplan-Meier curves and Cox regression analysis were employed to investigate the relationship between peripheral blood T lymphocyte subsets and PFS and OS. Results Compared with non-responder group, the baseline peripheral blood CD4+/CD8+ ratio was higher (P=0.038), while the CD8+T lymphocyte percentage was lower (P=0.036) in the responder group. Kaplan-Meier curves showed that a high baseline CD4+/CD8+ ratio was associated with long PFS and OS (P=0.001, P=0.023). Multivariate Cox analysis revealed that the baseline CD4+/CD8+ ratio was a significant predictor for PFS and OS. Additionally, a high post-treatment CD4+/CD8+ ratio and high CD4+T lymphocyte percentage were associated with long PFS (P=0.005, P=0.015), whereas a low post-treatment CD8+T lymphocyte percentage was associated with long PFS and OS (P=0.001, P=0.016). Conclusion The peripheral blood CD4+/CD8+ ratio can serve as a predictive factor for survival of patients with NSCLC treated with camrelizumab.

In order to investigate the mechanism of 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR)on liver bile acid(BAs)and lipid metabolism of dairy cows with fatty liver,A liver lip-id accumulation model was established by isolating primary calf hepatocytes and treating them with high concentration of non-esterified fatty acids(NEFA)in vitro.Then,HMGCR overex-pressed adenovirus(Ad-HMGCR)and overexpressed adenovirus control(Ad-GFP)were added.Hepatocyte triglyceride(TAG)was detected by the kit,lipid droplet changes were detected by lip-id droplet fluorescence,and BAs synthesis,fatty acid synthesis and oxidation factor changes were detected by real-time fluorescence quantitative PCR.The results showed that TAG content and lip-id droplet fluorescence were significantly reduced in Ad-HMGCR+NEFA group compared with Ad-GFP+NEFA group.Real-time fluorescence quantitative PCR results showed that CYP7A1,CYP8B1,CYP7B1 and CYP27A1 of hepatocyte BAs synthesis factors in Ad-HMGCR+NEFA group,BAs transporters ABCC2 and ABCB11 and fatty acid synthesis factors ACC1,FAS and SREBP1C were significantly lower than those in Ad-GFP+NEFA group.The levels of BAs syn-thesis factor FXR and lipid oxidation factor CPT1A in Ad-HMGCR+NEFA group were higher than those in Ad-GFP+NEFA group.The results showed that overexpression of HMGCR could significantly reduce BAs and lipid accumulation in the liver of dairy cows with fatty liver.

Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P＜0.05),and the number of falls was significantly increased(P＜0.001).The expression level of TH protein in brain tissue was significantly decreased(P＜0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P＜0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P＜0.05,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P＜0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P＜0.05,P＜0.001),the falling latency was significantly prolonged(P＜0.05,P＜0.01),the times of falls was significantly reduced(P＜0.001),the expression level of TH protein in brain tissue was significantly increased(P＜0.01,P＜0.001),and the level of serum TNF-α was significantly decreased(P＜0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P＜0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P＜0.01,P＜0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P＜0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

Objective:To evaluate the effect of operation duration on the pharmacokinetics of desflurane in the patients undergoing tumor resection.Methods:One hundred and fifty patients of both sexes, aged 18-75 yr, with body mass index of 19-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, in whom abnormal preoperative lung function was not found, undergoing elective surgery with general anesthesia from November 2019 to March 2020, were enrolled in this study.Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, cisatracurium besylate 0.2 mg/kg and propofol 2 mg/kg.The patients were tracheally intubated after mechanical ventilation.Anesthesia was maintained with inhalation of desflurane, the vaporizer dial was adjusted to 6% with fresh gas flow rate of 2 L/min, and sufentanil and cisatracurium besylate were intermittently injected intravenously according to the changes in hemodynamics and degree of muscle relaxation during operation.The duration required for the end-tidal concentration of desflurane reaching 0.5 minimum alveolar concentration (MAC), time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the volatile tank were recorded.The patients were divided into 3 groups according to the operation time: operation time <2 h group (group S), operation time 2-4 h group (group M), and operation time >4 h group (group L). Results:There were no significant differences among the 3 groups in the duration required for the end-tidal concentration of desflurane reaching 0.5 MAC, time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the vaporizer ( P>0.05). Conclusion:Operation duration does not affect the pharmacokinetics of desflurane in the patients undergoing tumor resection.

Objective:To investigate the application and effect of personalized teaching mode based on Xuexitong learning platform in physiology.Methods:Four parallel classes from the nursing specialty were randomized into two groups, of which the class 1 and class 2 were taken as the experimental group, and the class 3 and class 4 were taken as the control group, with 102 students in both groups. The students number of these two groups is both 102. The experimental group adopted the personalized teaching mode based on Xuexitong learning platform, with the features of preparation before the class, the teaching in class and testing after class; while the control group adopted the traditional teaching mode. The final results of students from the two groups were compared, and questionnaires were send out. The data were processed by SPSS 22.0 software and analyzed by rank-sum test.Results:The final scores of the students from the experimental group were better than those of the control group ( P<0.001). The experimental group was significantly better than the control group in improvement of self-learning, teamwork, personality development and medical literacy ( P<0.05). And there was no significant difference in the recognition of language expression ability between the two groups ( P>0.05). Conclusion:The personalized teaching based on Xuexitong learning platform can play an important role in developing the personalities of students and improving the educational effect of teaching students in accordance with their aptitude, which has a popularization significance in the teaching of physiology.

Objective:To explore the effect of cognitive behavior orientation group psychotherapy on coping style, time management and family function of middle school students with internet addiction, and provide theoretical basis for the internet addiction psychotherapy system.Methods:Based on IAT, 70 internet addiction middle school students were screened and divided into control group and experimental group according to random number table method.The control group was only given conventionally psychological and drug treatments, the experimental group participated in cognitive behavioral orientation group psychotherapy on the basis of the treatment of the control group.Thirty-two people in the control group and thirty-three people in the experimental group completed the treatment.Before and after treatment, the two groups of middle school students were evaluated by the internet IAT, the SCSQ, the ATMD and the FAD.Results:There was no significant difference in the scales between the two groups of internet addiction middle school students before treatment (all P>0.05). After the intervention of the experimental group, the differences in the positive response (1.89±0.51), negative response (1.55±0.51), time monitoring (58.39±12.10), time value (26.64±4.48), time efficacy (30.42±5.18), and roles(18.85±2.40), communication(24.18±3.77), behavior control (18.82±2.57) and general functioning(24.79±3.90) of FAD were statistically significant compared with the control group (1.62±0.44), (1.84±0.55), (52.09±11.72), (19.34±3.96), (21.91±6.13), (21.16±2.63), (26.09±3.75), (20.59±2.54), (28.69±3.68) and the pre-intervention period (1.46±0.48), (1.97±0.56), (48.73±13.46), (18.27±4.84), (20.00±5.79), (21.76±2.72), (26.58±3.86), (19.76±2.96), (29.27±4.76) (all P<0.05). There were significant differences in problem-solving (12.67±2.50) and affective responsiveness (14.03±3.73) scores of the FAD between the experimental group and the pre-intervention group (14.15±2.83), (14.61±3.66) (all P<0.05). There were significant differences in SCSQ and ATMD before and after treatment in the control group (all P<0.05). Conclusion:Cognitive behavior orientation group psychotherapy can optimize the coping style, ameliorate their time management ability and significantly improve the role, communication, behavior control and overall function of family function of middle school students with internet addiction.

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.