Purpose To identify the role of tyrosine kinase receptor Axl for anti-apoptosis which was induced by cisplatin (DDP) and methotrexate (MTX) chemotherapy and to analyze the relationship between P-Axl and apoptosis-related proteins in osteosarcoma.Methods Osteosarcoma cell lines MG63,143B and U2OS were used in apoptosis assays,Axl siRNA transfection,cytotoxicity assays,cell cycle analysis,etc.A total of 41 cases of osteosarcom patients were included for immunohistochemistry of EnVision two-step staining and clinico-pathological relative analysis.TUNEL assay was performed in ten cases for apoptosis detection.Results Among the osteosarcoma cell lines,Gas6/Axl could obviously protect tumor cells from apoptosis induced by DDP and MTX (P ＜ 0.05).Axl siRNA transfection enhanced cell apoptosis,whereas Gas6 prone to function upon previous knockdown by Axl siRNA.Among the 41 cases,the positive rate of P-Axl,BCL-2,and Bax was 85.4％,70.7％,and 36.6％,respectively.In contrast,the positive rate of them was 22.2％,11.1％,and 11.1％ in osteofibrous dysplasia,respectively.The expression levels of these apoptosisrelated factors were significantly higher in osteosarcoma than in osteofibrous dysplasia (P ＜ 0.05).Through clinico-pathological analysis,there were significant relationships between the survival status and BCL-2 or Bax expression (P ＜ 0.05).Pearson correlation analysis demonstrated that BCL-2 was positively correlated to P-Axl with statistical significance (r =0.842,P ＜ 0.0001).By Cox univariate analysis,BCL-2 or Bax was correlated with the patients' prognosis.TUNEL assay also demonstrated that P-Axl high expression inhibited apoptosis in osteosarcoma tissues.Conclusion Gas6/Axl protects osteosarcoma cells from the apoptosis induced by DDP and MTX chemotherapy and inhibits apoptosis in osteosarcoma tissue,possibly through the regulation of apoptosis-related protein BCL-2.

Objective To observe the changes of adiponectin (APN),chemerin and tumor necrosis factor-α (TNF-α) in subclinical hypothyroidism (SCH) rats,and to clarify the effect of L-thyroxine (L-T4) replacement therapy.Methods Sixty-five male Wistar rats were randomly divided into five groups via the random number table method:control group (n =10),SCH group A (n =15),SCH group B (n =15),SCH group C (n =15) and L-T4 treatment group (SCH + L-T4,n =10).Rats in groups SCH A,B and C were fed with 5,15 and 20 mg·kg-1·d-1 methimazole (MMI) once daily by gavage.The rats in SCH + L-T4 group were given 20 mg·kg-1·d-1 MMI once daily through gavage,after 8 weeks,6 μg·kg-1· d-1 of L-T4 was intragastrically added (50 μg/tablet) and the model was completed at the 16th week.The levels of serum APN,chemerin and TNF-α were measured via the enzyme linked immunosorbent assay (ELISA) method.The mRNA and protein levels of APN,chemerin and TNF-α in visceral adipose tissue of 5 groups were determined by real-time PCR (RT-PCR) and Western blotting,respectively.Results Compared with the control group [(202.20 + 17.27) ng/L,(143.70 ± 18.46) ng/L,(114.69 ± 4.18) μg/L],the serum chemerin levels in the SCH A,B,C groups were significantly higher [(314.33 ± 16.80),(355.00 ± 17.10),(365.00 ± 11.63) ng/L,P ＜0.05] and TNF-α levels also increased significantly [(222.60 ± 14.13),(279.20 ± 12.79),(288.30 ± 15.89) ng/L,P ＜0.05],and APN levels were significantly decreased [(77.21 ± 3.08),(68.58 ± 2.92),(59.45 ± 2.41) μg/L,P ＜0.05];but compared with SCH group C,the levels of chemerin and TNF-α in the SCH + L-T4 group were decreased [(260.07 ± 10.80),(178.40 ± 10.29) ng/L] and the level of APN [(102.35 ± 3.17) μg/L] was increased (P＜ 0.05).The mRNA and protein levels of APN in SCH A,B,C groups were significantly lower than those in the control group (P ＜0.05).The APN mRNA and protein levels in the SCH + L-T4 group were significantly higher than those in the SCH group C (P ＜ 0.05).The mRNA and protein levels of chemerin and TNF-α in the SCH A,B,C groups were higher than those in the control group (P ＜ 0.05).However,the mRNA and protein levels of chemerin and TNF-α in the SCH + L-T4 group were significantly lower than those in the SCH group C (P ＜ 0.05).Conclusion The expression levels of serum chemerin and TNF-α in SCH rats have increased,and APN levels decreased,but L-T4 can ameliorate these changes.

Objective:To assess the cardiac autonomic nervous function in elderly patients with frailty.Methods:Patients aged ≥ 65 years old admitted in Beijing Hospital from September 2018 to August 2019 were enrolled in this study. Clinical frailty score was used to assess the frailty. The cardiac autonomic modulation was evaluated by sinus heart rate turbulence analysis through 24 h electrocardiogram recording.Results:A total of 129 elderly patients were finally enrolled in this study with a mean age of (77.5±6.4) years, 58.1% of them were male. There were 53 patients in frail group and 76 patients in non-frail group. The age of the frailty group was significantly higher than that of the non-frailty group [(80.5±5.5) vs.(75.3±6.2)]; the prevalence of hypertension [84.9%(45/53)], heart failure [32.1%(17/53)] and peripheral vascular diseases [32.1%(17/53)] in the frailty group was significantly higher than that in the non-frailty group [65.8%(50/76), 1.3%(1/76), 17.1%(13/76); t=5.001, χ 2=5.879, 24.606, 3.921; all P<0.05]. Compared with non-frailty group, turbulence onset (TO) [-0.05(-0.92, 0.82)% vs. -0.74(-1.58, 0)%; Z=2.616, P=0.009] was significantly higher in frailty group, while turbulence slope (TS) [2.34(1.30, 5.00)ms/RR vs. 4.34(2.66, 6.39)ms/RR; Z=-3.048, P=0.002] was significantly lower. The rate of TO abnormality [49.1% (26/53) vs. 26.3%(20/76), χ 2=7.038, P=0.008] and TS abnormality [34.7%(29/53) vs. 21.0%(16/76); χ 2=15.579, P<0.001] in the frailty group was significantly higher than that in the non-frailty group. Multivariate logistic regression analysis showed that TO abnormality( OR=2.970, P=0.010, 95 %CI:1.300-6.785) and TS abnormality( OR=3.618, P=0.003, 95 %CI:1.565-8.364) were correlated with frailty. Conclusion:Cardiac autonomic nerve function may be impaired in elderly frail patients, and decreased vagal nerve tension may be presented.

Objective:To explore the intervention effect of humanistic management on anxiety and depression tendency of visiting physicians.Methods:The visiting physicians who began to further study in Beijing Anzhen Hospital, Capital Medical University from January 2016 to December 2018 were selected for humanistic management, and the visiting physicians from April 2013 to December 2015 were set as reference to conduct a questionnaire survey before and after the refresher training with the Hospital Anxiety and Depression Scale. Therefore, the visiting doctors all had the conventional refresher study management mode. On this basis, the intervention group established an individualized refresher study schedule, equipped the doctors with tutors, regularly visited the doctors and organized symposiums for them, assisted them to join the academic groups of the department, organized and coordinated the doctors to participate in the multi-disciplinary academic ward rounds, conducted negative emotional relief through the Balint groups, and integrated the cultural life of the refresher doctors into the cultural construction of the hospital and follow up the refresher doctors after the refresher training. SPSS 16.0 was used to perform t-test and variance analysis. Results:There was no difference in anxiety and depression scores between the two groups according to gender, type of refresher department, level of source hospital and length of study ( P > 0.05). Compared with the two evaluations in the intervention group, the second scores of anxiety for men and women [(5.90±1.37) vs . (6.48±1.87), (5.92±1.45) vs . (6.73±2.12)], doctors in each department [(5.50±1.23) vs . (6.76±2.35), (6.03±1.36) vs . (6.64±1.75), (5.98±1.50) vs . (6.64±2.15)], doctors from secondary and tertiary hospitals [(5.85±1.29) vs . (6.64±2.02), (6.00±1.50) vs . (6.78± 2.14)], the total score of doctors [(5.92±1.37) vs . (6.64±2.15), (5.92±1.47) vs . (6.68±1.98)] and the total score [(5.92±1.42) vs. (6.66±2.05)] were lower than the first evaluation score ( P<0.05). The second scores of depression for female doctors [(6.15±1.37) vs . (6.68±2.06)], doctors in medical laboratory department [(6.02±1.40) vs . (6.69±1.88)], doctors from tertiary hospital [(6.13±1.41) vs. (6.51±1.90)], doctor with different training durations [(6.04±1.42) vs . (6.50±2.02), (6.12±1.34) vs . (6.57±1.97)] and the total score of doctors [(6.09±1.37) vs . (6.54±1.99)] were lower than those of the first evaluation ( P < 0.05). The anxiety score of the second evaluation in the control group was higher in male physicians [(6.63±1.15) vs . (6.11±1.76)] than the first evaluation ( P < 0.05). Compared with the second evaluation data of doctors in the two groups, in terms of anxiety scores, the scores of doctors at all levels and total scores in the intervention group were lower than those in the control group ( P < 0.05); in terms of depression score, the scores of female visiting doctors, doctors from tertiary hospitals, doctors with refresher training duration of 6 months and total score were lower than those of the control group ( P < 0.05). Conclusion:The application of humanistic management to strengthen the management of refresher physicians can improve the psychological state of refresher doctors to a certain extent, especially alleviate the anxiety state, which is a worthy promotion of refresher management mode.

Objective:To assess the correlation between frailty and cardiac autonomic nervous system function in elderly patients.Methods:Elderly hospitalized patients aged 65 years and over were enrolled and assessed for frailty by using the clinical frailty scale.Cardiac autonomic modulation was evaluated by heart rate variability analysis through 24 h electrocardiogram recording.Results:A total of 180 elderly patients were enrolled in this study, including 66 patients with frailty and 114 patients without frailty.The mean age of the frailty group was higher than that of the non-frailty group(79.8±6.0 vs.75.0±6.3, t=5.030, P<0.001). The proportions of patients with hypertension, stroke/transient cerebral ischemia attack(TIA), heart failure and osteoarthritis were higher in the frailty group than in the non-frailty group(all P<0.05). Compared with the non-frailty group, the standard deviation of normal-to-normal intervals(SDNN)[103.0(76.0, 121.2) vs.107.5(92.0, 136.0), Z=-2.108, P=0.035], the standard deviation of the averages of NN intervals in all 5-min segments(SDANN)[86.0(67.7, 106.5) vs.97.5(78.0, 126.0), Z=-2.694, P=0.007], normalized low frequency(LFnorm)(53.1±13.0 vs.59.3±13.9, t=-3.024, P=0.003)and low frequency/high frequency(LF/HF)ratio[1.2(1.0, 1.4) vs.1.4(1.1, 1.7), Z=-3.041, P=0.002]were decreased and normalized high frequency(HFnorm)(36.8±9.2 vs.32.2±10.7, t=3.033, P=0.003)was increased in the frailty group.HFnorm in the frailty group was significantly higher than that in the non-frailty group.The incidents of SDANN<92 ms, LFnorm<50 nU, HFnorm>32 nU and LF/HF ratio<1.5 were higher in the frailty group than in the non-frailty group(59.1% or 39/66 vs.41.2% or 47/114, 42.4% or 28/66 vs.22.8% or 26/114, 72.7% or 48/66 vs.49.1% or 56/114, 84.8% or 56/66 vs.65.8% or 75/114, χ2=5.346, 7.660, 9.547, 7.664, P=0.021, 0.006, 0.002, 0.006). Logistic multivariate regression analysis showed that LFnorm, HFnorm and LF/HF ratio were correlated with frailty( OR=0.971, 1.039 and 0.333, all P<0.05), and HFnorm>32 nU and LF/HF ratio<1.5 were risk factors for frailty( OR=2.401 and 2.773, both P<0.05). Conclusions:Cardiac autonomic nerve system function is impaired in elderly frail patients, with the imbalance between the sympathetic and vagus nerves.Therefore particular attention should be paid to heart rate variability in elderly patients with frailty.

BackgroundObsessive-compulsive personality disorder and obsessive-compulsive disorder （OCD） are common psychological disorders with similar clinical symptoms， but the differences between the two need further clarification. ObjectiveTo explore the clinical features of and influencing factors of obsessive-compulsive personality disorder in patients with OCD， so as to provide references for further relevant clinical diagnosis and treatment. MethodsA total of 195 patients with OCD were selected as the research subjects， who received treatment at the outpatient and inpatient departments of the Affiliated Brain Hospital of Nanjing Medical University from July 2022 to December 2023 and met the diagnostic criteria for OCD in the International Classification of Diseases， tenth edition （ICD-10）. Evaluation was conducted by using the Yale-Brown Obsessive Compulsive Scale （Y-BOCS）， Personality Diagnostic Questionnaire-4+ （PDQ-4+）， Obsessive-Compulsive Inventory-Revised （OCI-R）， Beck Depression Inventory （BDI）， Beck Anxiety Inventory （BAI） and Sheehan Disability Scale （SDS）. In accordance with the score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4+， patients were divided into the OCD group with obsessive-compulsive personality disorder （n=58） and the OCD group without obsessive-compulsive personality disorder （n=137）. Pearson correlation analysis and Spearman correlation analysis were adopted to examine the correlation between clinical features and the score of the Obsessive-Compulsive Personality Disorder Scale. Multiple linear regression analysis was used to explore the influencing factors of OCD patients with obsessive-compulsive personality disorder. ResultsStatistically significant differences were observed between OCD patients with and without obsessive-compulsive personality disorder in the age， family history of mental illness， time without treatment， hoarding and ranking dimension scores in OCI-R， OCI-R total score， score of Obsessive-Compulsive Personality Disorder Scale in PDQ-4， and BDI score （P≤0.05）. OCD patients with obsessive-compulsive personality disorder in the time without treatment， OCI-R total score， hoarding and ranking dimension scores in OCI-R and BDI score are all positively correlated with the score of the Obsessive-Compulsive Personality Disorder Scale （r=0.120， 0.526， 0.364， 0.492， 0.414， P<0.05）. The results of multiple linear regression analysis showed that time without treatment （β=0.132， P<0.05）， hoarding dimension score （β=0.283， P<0.05） and ranking dimension score in OCI-R （β=0.418， P<0.05） were the influencing factors of OCD patients with obsessive-compulsive personality disorder. ConclusionOCD patients with obsessive-compulsive personality disorder may have longer untreated periods， more pronounced functional impairments in hoarding and sorting and more severe depressive symptoms. Untreated time， hoarding symptoms and sorting symptoms may be influencing factors for OCD patients with obsessive-compulsive personality disorder. ［Funded by Jiangsu Province Science and Technology Project （number， BE2021616；number， BE2022678）； Key Project of Nanjing Medical Science and Technology Development Fund （number， ZKX20029）］