【Objective】 To explore the dynamic change of depression in diabetic patients so as to provide evidence for early detection and warning of psychological problems in diabetic patients. 【Methods】 Based on the data from the China Health and Retirement Longitudinal Study （CHARLS）， the propensity score matching method was used to eliminate confounding factors in the study. The linear growth model， the nonlinear quadratic growth model， and the growth model without defined curve type were fitted respectively. According to the fitting indices of the models， the optimal solution of the growth function was determined to explore the changes of depression development in the diabetic patients. 【Results】 A total of 5 711 cases （5 380 cases in the non-diabetic group and 331 cases in the diabetic group） were included in the study. After propensity score matching， 1 621 cases （1 291 cases in the non-diabetic group and 330 cases in the diabetic group） were included and all confounding factors were balanced between the two groups. By fitting three growth curve models with latent variables， the results showed that the model without defined curve type was better than the other two models. The mean depression score for initial status in the non-diabetic and diabetic groups was 9.640 and 10.097， respectively， with significant inter-individual differences. During the follow-up period， the depression status of both groups showed a trend of decrease first and then increase， but the depression score was always lower in the non-diabetic group than in the diabetic group. At the same time， there was no individual difference in the rate of change between the two groups， and there was no statistical difference between the initial depression score and the subsequent slope of change. 【Conclusion】 Exploring the change track of depression status over time in diabetic patients， understanding the individual psychological change trend and further explaining the differences between individuals are of great significance for intervention on psychological status at different stages.

Objective:The standard treatment for inoperable locally advanced esophageal cancer is concurrent chemoradiotherapy, but the survival was not satisfied. Nituzumab is a humanized IgG monoclonal antibody against EGFR. The purpose of this study is to investigate the toxicity and efficacy of concurrent chemoradiotherapy combined with nituzumab for locally advanced esophageal cancer.Methods:We retrospectively reviewed the clinical data of locally advanced esophageal cancer who were treated with concurrent chemoradiotherapy combined with nituzumab in Peking University Cancer Hospital from June 2015 to June 2020. Kaplan- Meier method was used for analysis. Results:Thirty Patients were enrolled this study.After a median follow-up of 22.5 months, The objective response rate was 93%. The 1-year, 2-year, 3-year overall survival rates were 83%, 57% and 41%, with the progression-free survival rates 75%, 47% and 32%, with the local-recurrence free survival rates 83%, 53% and 37%, with the metastasis-free survival rates 75%, 51% and 36%, respectively.The incidence of grade≥3 hematological toxicity was 32%. There were 16% patients experiencing grade≥3 esophagitis.Conclusion:The preliminary result of concurrent chemoradiotherapy combined with nituzumab is effective and safe for patients with locally advanced esophageal cancer.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals’ reported in the active nucleic acid test screening might be false positives.

Objective To determine the expression of interleukin-6 (IL-6) in cystic lesions of patients with acne vulgaris,and to evaluate the in vitro effect of Propionibacterium acnes (P.acnes) on the production of IL-6 and activation of p38 mitogen-activated protein kinase (p38MAPK) in the human acute monocytic leukemia cell line THP-1.Methods Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of IL-6 in cystic lesions of 6 patients with acne vulgaris,as well as in skin tissues of 6 healthy persons.Some cultured THP-1 cells were divided into 5 groups to be treated with 2 × 106 CFU/ml,2 × 107 CFU/ml and 2 × 108 CFU/ml heat-killed P.acnes suspensions (P.acnes groups),100 μμtg/L lipopolysaccharide (LPS group) and RPMI 1640 medium (control group) respectively.After 1-,3-and 6-hour treatment,real-time fluorescence-based quantitative PCR was conducted to determine the mRNA expression of IL-6 in the above groups.Enzyme-linked immunosorbent assay (ELISA) was performed to detect the level of IL-6 in the culture supernatant of cells in the 2 × 108-CFU/ml P.acnes group,LPS group and control group at 24 hours after the treatment.Western blot analysis was conducted to determine the protein expression of p38MAPK and phosphorylated p38MAPK in the 2 × 108-CFU/ml P.acnes group after 15-,30-and 60-minute treatment,as well as in the LPS group after 30-minute treatment and in the control group.Some other THP-1 cells were divided into 3 groups:2 × 108-CFU/ml P.acnes group treated with 2 × 108 CFU/ml P.acnes suspensions,SB203580 (an inhibitor of p38MAPK) group treated with 20 μmol/L SB203580 for 30 minutes followed by the treatment with 2 × 108 CFU/ml P.acnes suspensions,and control group treated with RPMI 1640 medium alone.After 6-hour treatment,the mRNA expression of IL-6 in the above 3 groups was measured by real-time fluorescencebased quantitative PCR.Results The mRNA expression of IL-6 was significantly higher in the cystic lesions of acne vulgaris than in the normal skin tissues (3.680:±:0.790 vs.1.155 ± 0.250,t =3.047,P ＜0.05).Two-way analysis of variance showed that there were significant difference in the mRNA expression of IL-6 among the 2 × 106-CFU/ml,2 × 107-CFU/ml and 2 × 108-CFU/ml p.acnes groups,LPS group and control group (F =532.3,P ＜ 0.001,v =4),and the mRNA expression of IL-6 significantly differed among different time points (F =526.6,P ＜ 0.001,v =2).There were also significant differences in the IL-6 level in the culture supernatant of cells among the 2 × 108-CFU/ml p.acnes group ([1 618.22 ± 32.23] ng/L),LPS group ([3 212.06 ± 353.00] ng/L) and control group ([147.10 ± 0.53] ng/L;v =2,F =102.35,P ＜0.01).After 15-,30-and 60-minute treatment with 2 × 108 CFU/ml P.acnes suspensions,the protein expression of phosphorylated p38MAPK obviously increased.The mRNA expression of IL-6 in THP-1 cells was significantly lower in the SB203580 group than in the 2 × 108-CFU/ml p.acnes group (t =15.91,P =0.004).Conclusions The mRNA expression of IL-6 evidently increases in the cystic lesions of patients with acne vulgaris.P.acnes can activate the signaling molecule p38MAPK in THP-1 cells,and promote the production of IL-6 by THP-1 cells.

Objective To investigate the roles of Dectin-1 in phagocytosis of Candida albicans (C.albicans) by macrophage-like cells derived from a human acute monocytic leukemia cell line THP-1.Methods THP-1 macrophage-like cells served as the target cells,and were transfected with small interfering RNA (siRNA) targeting Dectin-1 to down-regulate the expression of Dectin-1 receptor (siRNA-Dectin-1 group).THP-1 macrophage-like cells transfected with nonsense siRNA (siRNA-NC) served as a negative control group.After transfection,the THP-1 macrophage-like cells in the above 2 groups were cocultured with heat-killed C.albicans separately.And then,fluorescence microscopy was performed to count THP-1 macrophage-like cells phagocytosing C.albicans,and flow cytometry was used to determine the mean fluorescence intensity (MFI) of dihydrorhodamine (DHR)-123 fluorescent cells.Statistical analysis was done by one-way analysis of variance (ANOVA) and t test with the SPSS19.0 software.Results After transfection with siRNA-Dectin-1,the mRNA and protein expression of Dectin-1 significantly decreased in THP-1 macrophage-like cells (t =26.163,P ＜ 0.001).After 1-,2-,4-hour co-culture of THP-1 macrophagelike cells with C.albicans,fluorescence microscopy showed that the phagocytosis rates of C.albicans by THP -1 macrophage-like cells were significantly lower in the siRNA-Dectin-1 group than in the negative control group (17.5％ vs.22.1％,18.6％ vs.24.3％,39.2％ vs.59.1％,respectively,all P ＜ 0.05),so were the percentage of THP-1 macrophage-like cells phagocytosing more than 3 C.albicans cells (2.2％ vs.4.7％,2.5％ vs.5.4％,5.1％ vs.8.3％,respectively,all P ＜ 0.05).After 30-minute,1-,2-and 4-hour co-culture of THP-1 macrophage-like cells with DHR-123-labelled C.albicans,flow cytometry showed that the MFI of C.albicans-phagocytosing cells was significantly lower in the siRNA-Dectin-1 group than in the negative control group (36.8 vs.45.7,54.3 vs.62.4,72.1 vs.84.9,93.6 vs.116.7,respectively,all P ＜ 0.05).Conclusion Dectin-1 receptor plays an important role in the phagocytosis of C.albicans by macrophages.

Objective To evaluate the effect of Aspergillus fumigatus on the expression of tumor necrosis factor-α (TNF-oα) and activation of intracellular signaling molecule p38 mitogen-activated protein kinase (p38MAPK) in a human acute monocytic leukemia cell line THP-1.Methods Cultured THP-1 cells (2 x 105/ml) were divided into 4 groups to be treated with Aspergillus fumigatus suspensions at concentrations of 106 and 107 colony-forming units (CFU)/ml (106-and 107-CFU/ml Aspergillusfumigatus groups),100 mg/L β-glucan (a positive stimulus,β-glucan group),culture medium (blank control group) respectively for 1,3 and 6 hours.Real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of TNF-α in the THP-1 cells in the above groups.Some other THP-1 cells were treated with 107 CFU/ml Aspergillusfumigatus suspensions (107-CFU/ml Aspergillusfumigatus group),β-glucan (β-glucan group) and culture medium (blank control group) separately for 24 hours,and enzymelinked immunosorbent assay (ELISA) was performed to detect the level of TNF-α in the culture supernatant of THP-1 cells.Western blot analysis was conducted to detect the levels of p38MAPK and phosphorylated p38MAPK in THP-1 cells after 15-,30-and 60-minute treatment with 107 CFU/ml Aspergillusfumigatus suspensions.After 2-hour incubation with the p38MAPK inhibitor SB203580 (20 μmol/L),some THP-1 cells were additionally treated with 107 CFU/ml Aspergillus fumigatus suspensions,β-glucan and culture medium separately for 6 hours,and those without SB203580 treatment served as the control group.Then,qPCR was performed to measure the mRNA expression of TNF-α in the THP-1 cells in the above groups.Results The mRNA expression of TNF-α significantly differed among the 106-and 107-CFU/ml Aspergillus fumigatus groups,β-glucan group and blank control group (F =110.983,P ＜ 0.001),and significantly increased over time (F =701.680,P ＜ 0.001).After 24-hour treatment with 107 CFU/ml Aspergillus fumigatus suspensions,the TNF-α level(6 236.30 ± 437.12 ng/L)significantly increased compared with the blank control group (132.10 ± 0.61 ng/L,P ＜ 0.01).Thirty minutes after the treatment with 107 CFU/ml Aspergillusfumigatus suspensions,the phosphorylated p38MAPK level significantly increased,but started to decrease at 60 minutes.The mRNA expression of TNF-α was significantly lower in the SB203580-treated Aspergillusfumigatus groups (3.83 ± 0.62) than in the SB203580-untreated Aspergillus fumigatus groups (187.23 ± 21.62).Conclusion After the treatment with Aspergillus fumigatus,human THP-1 cells can activate the signal molecule p38MAPK and secrete TNF-α,suggesting that monocytes may participate in the innate immune response to Aspergillusfumigatus infection.

Objective: To evaluate left ventricular (LV) dysfunction in patients with esophageal cancer (EC) during concurrent chemoradiotherapy (CCRT) using real-time three-dimensional speckle tracking echocardiography (3D-STE) and analyze its influence factors. Methods: Thirty-one patients with EC who received CCRT were enrolled in the study.Conventional echocardiography and 3D-STE were performed pre-CCRT and during CCRT (radiotherapy dose reached 40Gy). Three-dimensional parameters including LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) as well as global circumferential strain (GCS) were compared between pre-CCRT and during CCRT. The independent factors on left ventricular function parameters were analyzed. Results: There was no change on LV diameters, LV volumes and LVEF during CCRT (all P>0.05), while LV diastolic function indexes were impaired compared with those of pre-CCRT, demonstrated by the decreased E/A, Em/Am, and increased E/Em(all P<0.05). 3DGLS was also significantly decreased during CCRT compared with that of pre-CCRT (P<0.05), but no significant difference was found in 3DGCS (P>0.05). Multivariate linear regression analysis manifested that cardiac V40(the percentage of cardiac volume as radiotherapy dose reached 40Gy) was an independent determinant of LV 3DGLS in patients with esophageal cancer during CCRT (P<0.05). Conclusions LV GLS provided by real-time 3D-STE could sensitively detect CCRT-induced myocardial injury. Cardiac V40 is independently associated with LV 3DGLS during CCRT, representing the impact of radiotherapy on the subclinical LV function change.

Objective     To recognize the risk factors of unplanned re-interventions within 30 days after pediatric cardiac surgery and evaluate the outcome of re-interventions. Methods     We retrospectively analyzed the clinical data of 202 children in Fuwai Hospital between January 1, 2015 and August 31, 2017. There were 115 males and 87 females at average age of 32.4 months with range of 3 days to 14 years. Results     There were 202 children who underwent unplanned re-intervention during 30 days post-operation, including 54 re-adjustments of pulmonary blood flow, 34 re-corrections for residual cardiac abnormalities, 28 cardiopulmonary resuscitations, 38 for coagulation problems, 19 pericardial drainages, 11 palliative re-operations to deliver heart load and 6 diaphragmatic folds and 12 others. The mortality rate among children who underwent unplanned re-inventions after cardiac surgery was 10.9% (22/202). It was much higher than those free from re-interventions (0.7%). Time of mechanical ventilation was 284.3 (11–2 339) h, and mean ICU stay was 17.7 (1–154) d, significantly longer than those free from re-interventions at the same period. Conclusion     Unplanned re-interventions after pediatric cardiac surgery is associated with higher mortality rate and longer recovery time. Early identifying risk factors and re-intervention can reduce the complications and improve the prognosis.

Objective To evaluate effects of the yeast form of Sporothrix schenckii on activation of p38 mitogen-activated protein kinase (p38MAPK) and expression of interleukin-6 (IL-6) in macrophagelike THP-1 cells,which were differentiated from the human acute monocytic leukemia cell line THP-1.Methods THP-1 macrophage-like cells were divided into 3 groups to be treated with the yeast form of Sporothrix schenckii at a concentration of 2 × 106 colony-forming units (CFU)/ml (yeast form group),100 mg/L curdlan (curdlan group) and RPMI 1640 medium (blank control group) respectively.Real-time fluorescence-based quantitative PCR was performed to measure the mRNA expression of IL-6 in THP-1 macrophage-like cells in the above 3 groups after 3-and 6-hour treatment separately,and enzyme-linked immunosorbent assay (ELISA) to detect the level of IL-6 in the culture supernatant of THP-1 macrophagelike cells after 24-hour treatment.Western blot analysis was conducted to determine the protein expression of p38MAPK and phosphorylated p38MAPK (p-p38MAPK) in the above 3 groups after 30-and 60-minute treatment separately.Other THP-1 macrophage-like cells were pretreated with 100 nmol/L dexamcthasonc (a p38MAPK inhibitor) for 30 minutes,and then were divided into 3 groups to be treated with the yeast form of Sporothrix schenckii,curdlan and RPMI 1640 medium respectively,and changes in the level of pp38MAPK and mRNA expression of IL-6 were also detected.Statistical analysis was carried out with SPSS19.0 software by using one-way or multi-way analysis of variance and least significant difference (LSD) test.Results Significant differences in the mRNA expression of IL-6 in THP-1 macrophage-like cells were observed among the yeast form group,curdlan group and blank control group (F =5 552.22,P ＜0.001) after 3-hour treatment (56.81 ± 7.36,26.69 ± 1.22 and 0.97 ± 0.05,respectively) and 6-hour treatment (378.03 ± 16.67,276.24 ± 39.13 and 1.02 ± 0.04,respectively).Additionally,the yeast form group showed significantly higher mRNA expression of IL-6 after 6-hour treatment than that after 3-hour treatment (q =16.74,P ＜ 0.001).After 24-hour treatment,the level of IL-6 in the culture supernatant of THP-1 macrophage-like cells also significantly differed among the yeast form group,curdlan group and blank control group (59.96 ± 18.16 pg/L,91.01 ± 17.27 pg/L,5.50 ± 2.30 pg/L,respectively;F =26.62,P ＜ 0.01),and was significantly higher in the yeast form group than in the blank control group (P ＜ 0.01).After 30-and 60-minute treatment,the protein expression of p-p38MAPK was significantly higher in the yeast form group than in the blank control group (both P ＜ 0.01).Moreover,the mRNA expression of IL-6 (4.46 ± 1.03 vs.493.52 ± 113.87,P ＜ 0.001) and protein expression of p-p38MAPK (2.29 ± 0.37 vs.4.55 ±0.46,q =10.81,P ＜ 0.01) were both significantly lower in the yeast form group with dexamethasone pretreatment than in that without dexamethasone pretreatment.Conclusion In vitro treatment with the yeast form of Sporothrix schenckii can enhance the expression of IL-6 in human THP-1 macrophage-like cells by activating the p38MAPK signaling pathway.