Objective To investigate the effects of berberine on UCP2 expression and the mitochondrial dy-namics in skeletal muscle and kidney in mice with ischemia reperfusion injury (IRI) of lower limb.Methods Thirty male Kunming mice were randomly divided into the negative control group,the positive control group,and low,medium and high doses berberine intervention groups.The mice in all experimental groups constructed the ischemia reperfusion injury model of lower limbs by tourniquet,different doses of berberine solution were injected intraperitoneally for intervention,while the ischemia repeating supply group used normal saline for re-placement.The HE staining was used to detect the pathological conditions of skeletal muscle and kidney,PCR and Western blot were used to detect the gene and protein expression levels of UCP2,FIS1,DRP1,Mfn1 and Mfn2,and the changes of SOD,MDA and GSH were detected by kit.Results After IRI intervention in the both lower extremities,the inflammatory cell infiltration occurred in both skeletal muscle and kidney,and the cell structure of skeletal muscle showed the damage changes.Meanwhile,the gene and protein expressions lev-els of UCP2,FIS1 and DRP1 and the levels of GSH and SOD in skeletal muscle were significantly increased (P<0.05),while the gene and protein expression levels of Mfn1 and Mfn2 and the levels of MDA were signif-icantly decreased (P<0.05).The increase of UCP2 and DRP1 gene and protein expression levels in kidney was different (P<0.05).Berberine could up-regulate the UCP2 gene expression in skeletal muscle and the pro-tein expression in skeletal muscle (P<0.05).At the same time,DRP1 gene and protein were significantly inhibited in the kidney tissue (P<0.05),but which in skeletal muscle had no significant change.Conclusion IRI of skeletal muscle of lower extremity in mice leads to severe oxidative stress injury,mitochondrial dynamic imbalance and inflammatory damage of kidney in the injured parts.The therapeutic effect of berberine on skeletal muscle and kidney IRI may be achieved by inhibiting oxidative stress injury,in which its protective effect on kidney may also be related to inhibit the expression of DRP1 after UCP2 up-regulation,thus limit the mitochondrial fission and slow down the development of injury.

With the intensive aging of the population, it's imperative and important to train a number of geriatric specialists. Essential clinical knowledge and skills as well as accomplishment of medical humanistic spirit are core competences of an eligible geriatrician. The standardized training of geriatric specialists is facing a few challenges such as incomplete comprehension of the training program and trainees, a lack of enough trainees, and a lack of standardized management for the program. An efficient social support system, a normative educational training system, an effective supervision and evaluation system, first-class teaching staff, and qualified trainees are important guarantees for the standardized training program.

Leukemia is a common, multiple and dangerous blood disease, whose early diagnosis and treatment are very important. At present, the diagnosis of leukemia heavily relies on morphological examination of blood cell images by pathologists, which is tedious and time-consuming. Meanwhile, the diagnostic results are highly subjective, which may lead to misdiagnosis and missed diagnosis. To address the gap above, we proposed an improved Vision Transformer model for blood cell recognition. First, a faster R-CNN network was used to locate and extract individual blood cell slices from original images. Then, we split the single-cell image into multiple image patches and put them into the encoder layer for feature extraction. Based on the self-attention mechanism of the Transformer, we proposed a sparse attention module which could focus on the discriminative parts of blood cell images and improve the fine-grained feature representation ability of the model. Finally, a contrastive loss function was adopted to further increase the inter-class difference and intra-class consistency of the extracted features. Experimental results showed that the proposed module outperformed the other approaches and significantly improved the accuracy to 91.96% on the Munich single-cell morphological dataset of leukocytes, which is expected to provide a reference for physicians' clinical diagnosis.
Humans ; Blood Cells ; Leukocytes ; Leukemia ; Electric Power Supplies ; Recognition, Psychology

Objective:To explore genetic etiology and evaluate antifungal immunity in a patient with recurrent cervical lymphadenitis caused by Candida albicans. Methods:Next-generation sequencing was performed to screen susceptibility genes for mycosis in a patient with recurrent cervical lymphadenitis caused by Candida albicans and his parents. Peripheral blood mononuclear cells (PBMCs) and neutrophils were extracted from the patient and 6 healthy controls, and subjected to in vitro co-culture with Candida albicans. Western blot analysis was performed to determine the expression of caspase recruitment domain-containing protein 9 (CARD9) in PBMCs of the patient, enzyme-linked immunosorbent assay to detect levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -6, IL-17A, IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the co-culture medium, and a colony-counting method was used to detect the survival rate of Candida albicans after treatment with neutrophils. Statistical analysis was carried out by using t test for comparisons between two groups. Results:Two compound heterozygous mutations were identified in the CARD9 gene of the patient, including c.68C>A (p.S23X) in exon 2 inherited from his father and c.820dupG (p.D274Gfs*61) in exon 6 inherited from his mother. Western blot analysis showed that the relative expression level of CARD9 protein in the PBMCs was 0.41 ± 0.07 in the healthy control group, but CARD9 expression was absent in the patient. After stimulation with heat-inactivated Candida albicans spores, the levels of TNF-α, IL-6, IL-17A, IL-1β and GM-CSF secreted by PBMCs of the patient were significantly lower than those by PBMCs of the healthy controls (all P < 0.001). After 30- and 120-minute in vitro co-culture with neutrophils, the survival rates of Candida albicans were significantly higher in the patient (78.00%, 74.00%, respectively) than in the healthy controls (70.91% ± 1.75%, 34.55% ± 5.35%, t = 3.74, 6.99, respectively, both P < 0.05) . Conclusion:Compound heterozygous mutations were identified in the CARD9 gene of the patient with recurrent cervical lymphadenitis caused by Candida albicans, which led to the absence of CARD9 protein expression, and the patient had a defect in the immunity against Candida albicans.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

OBJECTIVE：To study the compositi on of the volatile oil from Compound chaihu guizhi decoction ，and to evaluate its in vitro anti-proliferative activity on human lung adenocarcinoma A 549 cells. METHODS ：The volatile oil from Chaihu guizhi decoction was extracted according to the steam distillation method of general rules 2004 in the 2015 edition of Chinese Pharmacopoeia（part Ⅳ）. The volatile oil components were analyzed by GC-MS combined with Kováts index ，and the relative content of each component was calculated by peak area normalization method. Using different concentrations of cisplatin （4，8， 16，32，64 mg/L）as positive control ，MTT assay was used to detect the inhibitory effects of different concentrations of volatile oil from Chaihu guizhi decoction （25，50，100，200，400 mg/L）on in vitro proliferation of A 549 cell after 48 h of treatment. Negative control group （with cells but without drugs ）was set up. RESULTS ：A total of 71 chemical components were isolated from the volatile oil ，among which there were 59 compounds identified ，sum of peak areas accounting for 84.99％ of the total peak area. The compounds with relatively high content included ar-curcumene （17.65％），β-bisabolene（9.57％），β-ocimene（7.05％）， α-curcumene（5.35％），2，5-dimethylbenzaldehyde（4.24％），linalyl isobutyrate （2.70％），α-cedrene（2.48％），δ-cadinene （2.07％）. Compared with negative control group ，the proliferation rate of cells were decreased significantly in 4-64 mg/L cisplatin groups and 25-400 mg/L volatile oil from Chaihu guizhi decoction groups （P＜0.05）. IC 50 of cisplatin and volatile oil from Chaihu guizhi decoction to in vitro proliferation of A 549 cells were 10.150 and 73.526 mg/L. CONCLUSIONS ：The volatile oil from Chaihu guizhi decoction mainly includes ar-curcumene ，β-bisabolene，β-ocimene，α-curcumene，which shows certain inhibitory effect on in vitro proliferation of A 549 cells.

Objective:To establish the sex-, age-and season-specific (month) reference intervals (RI) for thyroid stimulating hormone (TSH) measurement by big data and indirect method in adults.Methods:TSH data of anonymous patients were collected from Beijing Chaoyang Hospital Affiliated to Capital Medical University in 2016, the data were selected and outliers were removed. Indirect methods (Hoffmann method and Bhattacharya method) were used to calculate TSH reference intervals of whole population, different genders, ages and seasons (months). TSH RI from two indirect methods of total population, selected population, physical examination population was compared with RI from reagent instruction according to reference change value ( RCV) based on biological variability. Results:A total of 61 599 records were obtained from 90 699 records including 18 776 males and 42 823 females. The TSH RI were obtained by Hoffmann method: the whole population, 0.59-5.59 μIU/ml (1 μIU/ml=1 mIU/L), male, 0.53-5.16 μIU/ml, female, 0.59-6.11 μIU/ml. The upper limits of TSH RI were higher with age and in winter (January): 18-30 years old, 0.62-5.57 μIU/ml, 71-80 years old, 0.49-6.45 μIU/ml; January, 0.59-6.40 μIU/ml, August, 0.60-5.56 μIU/ml; The RI of TSH by Bhattacharya method: the whole population, 0.58-5.80 μIU/ml, male, 0.55-5.02 μIU/ml, female, 0.62-6.21 μIU/ml. The upper limits of TSH RI were also higher with age and in winter (January): 18-30 years old, 0.65-5.67 μIU/ml, 71-80 years old, 0.46-5.99 μIU/ml, January: 0.61-6.52 μIU/ml, August: 0.61-5.69 μIU/ml. Compared to RI from reagent instruction, the differences of TSH RI from two indirect methods of total population, selected population, physical examination population were acceptable.Conclusions:TSH RI was established by indirect method. With the increase of age and winter, the upper limit of TSH reference interval tends to increase.

The outbreak of 2019 Novel Coronavirus (2019-nCoV) has spread from Wuhan to the whole country. After the Spring Festival, workers will return to workplace and students will return to school. There is an increasing risk of 2019-nCoV cases being imported into provinces and cities. In order to promote the prevention and control of 2019-nCoV infection, reduce the risk of transmission in medical institutions, and ensure medical quality and medical safety, it is necessary to carry out the detection test of 2019-nCoV in biosafety class II laboratory. In order to achieve the goal of zero infection of the laboratory personnel, different preventive measures should be taken to assess the risk of the experimental activities.

Objective: To explore the ability of computed-tomography (CT) radiomic features to predict the Epidermal growth factor receptor (EGFR) mutation status and the therapeutic response of advanced lung adenocarcinoma to EGFR- Tyrosine kinase inhibitors (TKIs) treatment. Methods: A retrospective analysis was performed on 253 patients diagnosed as advanced lung adenocarcinoma, who underwent EGFR mutation detection, and those with EGFR sensitive mutation were treated with TKIs. Using the Lasso regression model and the 10 fold cross-validation method, the radiomic features of predicted EGFR mutation status and the screening of TKIs for sensitive populations were obtained. 715 radiomic features were extracted from unenhanced, arterial phase and venous phase, respectively. Results: The area under curve (AUC) values of the multi-phases including unenhanced, arterial phase and venous phase of the EGFR mutation status validation group were 0.763, 0.807 and 0.808, respectively. The number of radiomic features extracted from the multi-phases were 5, 18 and 23, respectively, which could distinguish the EGFR mutation status. The AUC values of the multi-phases of the EGFR-TKIs sensitive validation group were 0.730, 0.833 and 0.895, respectively. The number of radiomic features extracted from the multi-phases were 3, 7 and 22, respectively, which can be used to screen the superior population for TKIs treatment. The efficiency of radiomic features extracted from venous phase in predicting EGFR mutant status and EGFR-TKIs sensitivity was significantly superior than those of unenhanced and arterial phase. Conclusions The radiomic features of CT scanning can be used as the radiomics biomarker to predict the EGFR mutation status of lung adenocarcinoma and to further screen the dominant population in TKIs therapy, which provides the basis for targeted therapy.

Objective: To analyze the influence of cognition on suicidal ideation in patients with major depressive disorder. Methods: A total of 108 inpatients with major depressive disorder from January 2017 to September 2018 in Beijing Huilongguan Hospital were enrolled.They were divided into suicidal ideation group (n=42) and non-suicidal ideation group (n=66) by the self-rating idea of suicide scale (SIOSS). Cognition was assessed by Repeatable Battery for the Assessment of Neuropsychological Status(RBANS). The general situation was assessed by self-made general situation questionnaire.The related factors were analyzed by Logistic regression. Results: (1) The rate of suicidal ideation was 44.4% in patients with major depressive disorder.(2) The total score of RBANS and five-factor scores of RBANS in suicidal ideation group were lower than those in non-suicidal ideation group(total RBANS score(63.0±7.9) vs (73.8±7.7); immediate memory: (62.7±8.8) vs (70.8±7.6); visual span: (67.2±10.0) vs (72.7±9.8); speech function: (83.3±13.8) vs (91.5±4.5); attention: (85.3±11.9) vs (99.9±8.5); delayed memory: (53.5±7.7) vs (62.3±9.7), F=6.335-46.660, P<0.05). (3)Logistic regression showed, years of education were risk factors for suicidal ideation(β=0.289, P=0.013, OR=1.335, 95%CI=1.063-1.676), RBANS attention factor(β=-0.161, P=0.000, OR=0.851, 95%CI=0.778-0.931)and RBANS delayed memory factor score(β=-0.151, P=0.006, OR=0.860, 95%CI=0.772-0.957)were protective factors for suicidal ideation. Conclusion Cognitive function has an impact on suicide ideation of depressive patients, mainly attention and delayed memory are protective factors for suicide ideation.