[Automated cephalometric landmark identification and location based on convolutional neural network].

Objective: To develop an automated landmark location system applicable to the case of landmark missing. Methods: Four and eighty-one lateral cephalograms, which contained 240 males and 241 females, with an average age of (24.5±5.6) years, taken from January 2015 to January 2021 in the Department of Orthodontics, Capital Medical University School of Stomatology, and met the inclusion criteria were collected. Five postgraduate orthodontic students were the annotators to manually locate 61 possible landmarks in 481 lateral cephalograms. Two assistant professors in the department as reviewers performed calibration. Two professors as arbitrators, made final decision. Data sets were established (341 were used as training set, 40 as validation set, and 100 as test set). In this paper, an automatic landmarks identification and location model based on convolutional neural networks (CNN), CephaNET, was developed. The model was trained by feeding the original image into the feature extraction module and convolutional pose machine (CPM) module to locate landmarks with high accuracy using deep supervision. Training set was enhanced to 1 684 images by histogram equalization, cropping, and adjustment of brightness. The model was trained to compare the Gaussian heat maps output from the network with the set threshold to identify landmark missing cases. Test set of 100 lateral cephalograms was used to test the accuracy of the model. The evaluation criteria used were success detection rate of missing landmark, mean radial error (MRE) and success detection rate (SDR) in the range of 2.0, 2.5, 3.0, 3.5 and 4.0 mm. Results: The model identified and located 61 commonly used landmarks in 0.13 seconds on average. It had an average accuracy of 93.5% in identifying missing landmarks. The MRE of our testing set was (1.19±0.91) mm. SDR of 2.0, 2.5, 3.0, 3.5 and 4.0 mm were 85.4%, 90.2%, 93.5%, 95.4%, 97.0% respectively. Conclusions: The model proposed in this paper could adapt to the absence of landmark in lateral cephalograms and locate 61 commonly used landmarks with high accuracy to meet the requirements of different cephalometric analysis methods.

[Early identification and influencing factors of post-traumatic stress disorder in high-stress rescue workers].

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.

[Study on static parameters of internal nasal valve in 3-dimensional model of nasal cavity space].

Objective: To identify the internal nasal valve (INV) and to evaluate its key parameters in the established 3D models of nasal cavity space via Mimics from CT images, in order to provide evidence for quantitative diagnosis of nasal valve compromise. Methods: A total of 32 Han adults without nasal diseases who underwent maxillofacial CT test in Shanghai Ninth People's Hospital from January 2015 to December 2018 were retrospectively recruited, including 16 males and 16 females, with the age ranged from 20 to 80 years (50% age<50 years old). Maxillofacial CT images were used to create 3D model of nasal cavity space. The INV was identified and the following parameters were measured: the angle between the INV and the nasal bone (θINV-B), unilateral cross-sectional area of the INV (AINV-R, AINV-L), total cross-sectional area of the INV (AINV), unilateral height of the INV (HINV-R, HINV-L), unilateral nasal valve angle (αINV-R, αINV-L), and the sum of nasal valve angle (αINV). The AINV in our study was compared with the results of the previously adopted planes (PlaneC, perpendicular to the hard palate and PlaneB, plane perpendicular to the nasal bone). The parameters above were compared among genders, age and race groups. SPSS 26 and GraphPad Prism 9 software were used for statistical analysis and mapping of data. Results: The AINV in our study was (214.87±52.94) mm², which was significantly less than that of PlaneC (254.97±47.80) mm² and PlaneB (226.07±57.36) mm². The measured parameters were as follows: θINV-B was (82.07±7.06)°; AINV-R was (112.66±31.39) mm²; AINV-L was (102.21±27.14) mm²; AINV was (214.87±52.94) mm²; HINV-R was (24.87±4.62) mm; HINV-L was (24.35±4.86) mm; αINV-R was (20.48±2.99)°; αINV-L was (19.65±3.82)°; αINV was (40.13±6.24)°. The AINV-R was larger than AINV-L (t=2.33, P<0.05); The HINV, AINV-R, AINV-L and AINV of males were more than those of females (t value was 5.77, 3.21, 2.91 and 3.52, respectively, all P<0.01). The AINV of the young group (<50 years) was larger than that of the old group (t=2.83, P<0.01); The θINV-B was different between the Han people and the Caucasian (t=2.92,P<0.01). The αINV of the Han people was larger than that of Caucasians (Z=-6.92, P<0.01), but the HINV was smaller (Z=-3.89, P<0.01). Conclusion: The AINV carried out in 3D models of nasal cavity space is significantly smaller than that obtained by the previous methods of CT evaluation. INV static parameters differ among genders, age and race groups.

[Variations in fecal microbiota of first episode schizophrenia associated with clinical assessment and serum metabolomics].

OBJECTIVE: To explore the role of the microbiota in drug naïve first-onset schizophrenia patients and to seek evidence from multidimensional longitudinal analyses of the intestinal microbiome and clinical phenotype with antipsychotic drugs (APDs) therapy. METHODS: In this study, 28 drug naïve first onset schizophrenia patients and age-, gender- and education-matched 29 healthy controls were included, and the patients were treated with APDs. We collected fecal and serum samples at baseline and after 6 weeks of treatment to identify the different microbiota strains and analyse their correlation with clinical symptoms and serum metabolites. The 16S rRNA genes of the gut microbiota were sequenced, and the diversity and relative abundance at the phylum and genus levels were analyzsed in detail. The PANSS score, BMI changed value, and serum metabolome were included in the data analyses. RESULTS: A multiomics study found a potential connection among the clinical phenotype, microbiota and metabolome. The species diversity analyses revealed that the alpha diversity index (chao1, ACE, and goods_coverage) in the schizophrenia APDs group was significantly lower than that in the control group, and the schizophrenia group had clear demarcation from the control group. The microbiota composition analysis results showed that the relative abundance of the genera of Bacteroides, Streptococcus, Romboutsia, and Eubacterium ruminantium group significantly changed after APDs treatment in the schizophrenia patients. These strains could reflect the APDs treatment effect. More genera had differences between the patient and control groups. The LEfSe analysis showed that Prevotella_9 and Bacteroides were enriched in schizophrenia, while Blautia, Dialister, and Roseburia were enriched in the control group. The correlation analysis between microbiota and clinical symptoms showed that Bifidobacterium in schizophrenia was positively correlated with the PANSS reduction rate of the general psychopathology scale. The BMI changed value was positively correlated with the alteration of Clostridium_sensu_stricto_1 during treatment and the baseline abundance of Bacteroides. Moreover, metabolomic data analysis revealed a significant correlation between specific genera and metabolites, such as L-methionine, L-proline, homovanillic acid, N-acetylserotonin, and vitamin B6. CONCLUSION: Our study found some microbiota features in schizophrenia patients and healthy controls, and several strains were correlated with APDs effects. Furthermore, the multiomics analysis implies the intermediate role of microbiota between antipsychotic effects and serum metabolites and provides new evidence to interpret the difference from multiple levels in the pathogenesis and pharmacological mechanism of schizophrenia.

[Value of heart rate-blood pressure product of multiplication for identifying compensated shock in children].

Objective: To estimate the predictive value of heart rate (HR)-blood pressure (BP) products of multiplication for compensated shock in children. Methods: The study population consisted of 99 children with shock who had lactate measured before receiving vasopressor agents in Department of Critical Care Medicine of Children's Hospital, Capital Institute of Pediatrics from October 2015 to March 2021. The clinical data including the HR, BP, HR to BP ratio, HR-BP product and lactate at admission and after the correction of shock, as well as the 28-day mortality were collected. According to the outcome at the 28th day, the patients were divided into survival group and non-survival group. Comparisons between groups were performed with unpaired Student t test, or Mann-Whitney U test, or chi-square test. Pearson correlation analysis was used to analyze the correlations between lactate and HR, BP, HR to BP ratio and HR-BP product, respectively. Receiver operating characteristic (ROC) curve was analyzed to evaluate the predictive values of HR, BP, HR to BP ratio and HR-BP product for lactate greater than 2 mmol/L. Results: In these 99 children, 49 were males, and the median age was 3.8 (0.7-6.0) years. The most common type of shock was septic shock (61 cases, 62%), followed by cardiogenic shock (12 cases, 12%), hemorrhagic shock (12 cases, 12%), Kawasaki disease shock syndrome (8 cases, 8%) and anaphylactic shock (6 cases, 6%). Sixty-six patients (67%) survived, and 33 patients (33%) died. ROC curve showed that the area under curves (AUC) of lactate (optimal cutoff value 3.15 mmol/L, sensitivity 96.0%, specificity 54.4%, P<0.01) and HR to systolic blood pressure ratio (HR/SBP) (optimal cutoff value 2.0 times/(min·mmHg), sensitivity 62.5%, specificity 69.0%, P = 0.03) for predicting adverse outcome were 0.769 and 0.649, respectively. There were significant correlations between lactate and HR to diastolic blood pressure (DBP) ratio, HR to mean blood pressure (MBP) ratio, SBP, HR/SBP, MBP, DBP and HR (r= 0.476, 0.452, -0.444, 0.425,-0.410, -0.364, 0.177, all P<0.01), while no significant correlation was found between lactate and the products of HR and BP(all P>0.05). HR/SBP performed better than the other six parameters for predicting lactate>2 mmol/L, with the AUC of 0.872 and the optimal cutoff value of 1.4 bpm/mmHg (sensitivity 92.1%, specificity 70.9%, P<0.01). When MBP was greater than or equal to 65 mmHg, MBP × HR, DBP × HR, SBP × HR, HR, HR/SBP, HR/MBP and HR/DBP were significantly correlated with lactate (r= 0.706, 0.705, 0.669, 0.626, 0.555, 0.502, 0.446, all P<0.01). And MBP × HR performed better for predicting lactate>2 mmol/L than the other six parameters, with the AUC of 0.974 and the optimal cutoff value of 9446 bpm × mmHg (sensitivity 100.0%, specificity 90.9%, P<0.01). Conclusions: The product of HR and BP, especially the MBP × HR, shows higher predictive values for abnormally elevated lactate in children with compensated shock than the HR/SBP does. It is worth recommending for early identification of compensated shock in children.

Can Psychosocial Intervention Suppress Testosterone and Triglycerides Among Women With Polycystic Ovary Syndrome? A Feasibility Trial.

Women with polycystic ovary syndrome (PCOS) suffer significant psychological distress, which may activate the hypothalamus-pituitary-ovary axis and further affect their physiological state. They often experience elevated levels of testosterone and triglycerides. Considering reports of psychological distress among women with PCOS, this study aimed to develop a psychosocial intervention to improve their emotional and physical health, particularly in Chinese society. This pilot study employed the Integrative Body-Mind-Spirit (I-BMS) intervention model for women with PCOS in China. After a 2 h health information session, 18 participants were randomly assigned to the I-BMS group (9) or the control group (9). The intervention group received 6 weekly, 3 h I-BMS sessions. Pre- and post-blood tests and psychosocial questionnaires were collected from all participants. Retention to treatment was high with 79.6% treatment adherence gained and an overall average of five sessions completed. Compared with the control group, depression and anxiety symptoms reduced significantly for those in the intervention group (d = -1.24, p < 0.05 and d = -1.33, p < 0.01), their health-related quality of life improved significantly (d = 1.02, p < 0.01) both at post-intervention and 3 month follow-up, and their testosterone and triglycerides levels reduced significantly (d = -0.97, p < 0.001 and d = -0.41, p < 0.05) after joining the intervention. The I-BMS model is feasible and appears promising in improving psychological health, and reducing testosterone and triglyceride levels, in women with PCOS in China. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR1900027606.

[Value of ATP synthase C subunit in predicting cardiac function and outcomes of sepsis].

Objective: To investigate the value of serum mitochondrial ATP synthase C subunit level in the evaluation of cardiac functional status and prognosis in patients with sepsis. Methods: A total of 165 sepsis patients admitted to the Emergency Intensive Care Unit (EICU) of the First Affiliated Hospital of Wenzhou Medical University from January 1, 2017 to December 31, 2018 were included, there were 103 males (62.4%) and 62 females (37.6%) with an age of (63±14) years. Human ATP synthase lipid binding protein (ATP5G1) ELISA kit was used to detect the level of serum ATP synthase C subunit within 24 h after admission to EICU, and compared with that in 45 healthy subjects. Clinical data of patients were collected and divided into groups according to different left ventricular ejection fraction (LVEF) and clinical outcomes. The differences in clinical indicators among each group were compared to evaluate the value of serum ATP synthase C subunit level in the evaluation of cardiac functional state and prognosis of patients with sepsis, and the independent risk factors for cardiac functional state and prognosis of patients with sepsis were analyzed. Results: Compared with the control group, the level of serum ATP synthase C subunit in the sepsis group was higher ((116±62) µg/L vs (77±34) µg/L, P<0.001). Compared with normal cardiac function group, the level of serum ATP synthase C subunit in septic cardiac dysfunction group was higher (P<0.001). Compared with the survival group, the level of serum ATP synthase C subunit in the death group was higher (P<0.05). The receiver operating curve (ROC) was drawn to analyze the value of ATP synthase C subunit, creatine kinase isoenzyme (CK-MB), B-type natriuretic peptide (BNP), troponin I (cTnI), left atrial end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic volume, left ventricular end systolic volume in evaluating the cardiac function in patients with sepsis, and the area under the curve (AUC) was 0.928, 0.661, 0.837, 0.814, 0.703, 0.831, 0.794 and 0.765, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 139.44 ng/L, 100% and 75.2%, respectively. ROC was drawn to analyze the prognostic value of age, urea nitrogen (BUN), ATP synthase C subunit, APACHEⅡ score and SAPSⅡ score in patients with sepsis, and the AUC was 0.719, 0.772, 0.656, 0.868 and 0.884, respectively. The cut-off value, sensitivity and specificity of ATP synthase C subunit in it was 131.24 ng/L, 61.9% and 68.7%, respectively. Logistic regression analysis showed that age, BUN, ATP synthase C subunit, cardiac dysfunction, APACHEⅡ score and SAPS Ⅱ score were independent risk factors for the prognosis of patients with sepsis. Conclusion: The level of serum ATP synthase C subunit is closely related to cardiac dysfunction in patients with sepsis, and can effectively predict the prognosis of patients with sepsis.

Effects of subacute ruminal acidosis on colon epithelial morphological structure, permeability, and expression of key tight junction proteins in dairy goats.

The hindgut epithelial barrier plays an important role in maintaining absorption and immune homeostasis in ruminants. However, little information is available on changes in colon epithelial barrier structure and function following grain-induced subacute ruminal acidosis (SARA). The objective of this study was to investigate the effects of grain-induced SARA on colon epithelial morphological structure, permeability, and gene expression involved in epithelial barrier function. Twelve mid-lactating (136 ± 2 d in milk; milk yield = 1.68 ± 0.15 kg/d) Saanen dairy goats with 62.13 ± 4.76 kg of body weight were randomly divided into either the control (CON) treatment (n = 6) or SARA treatment (n = 6). The CON goats were fed a basal diet with a nonfiber carbohydrates to neutral detergent fiber ratio of 1.15 for 60 d. The SARA goats were fed 4 diets with increasing nonfiber carbohydrates to neutral detergent fiber ratio at 1.15, 1.49, 2.12, and 2.66 to induce SARA, with each diet (referred to as period) being fed for 15 d, including 12 d for adaptation and 3 d for sampling. Continuous ruminal pH recordings were used to diagnose the severity of SARA. Additionally, colonic tissues were collected to evaluate the epithelial morphological structure, permeability, and expression of tight junction proteins using transmission electron microscopy, Ussing chamber, quantitative real-time PCR, and Western blotting. Profound disruption in the colonic epithelium was mainly manifested as the electron density of tight junctions decreased, intercellular space widened, and mitochondria swelled in SARA goats. Colon epithelial short-circuit current, tissue conductance, and the mucosal-to-serosal flux of fluorescein isothiocyanate-dextran 4 kDa were increased and potential difference was decreased in SARA goats compared with CON goats. Subacute ruminal acidosis increased mRNA and protein expression levels of CLDN1 and OCLN in the colonic epithelium. Overall, the data of the present study demonstrate that SARA can impair the barrier function of the colonic epithelium at both structural and functional levels, which is associated with severe epithelial structural damage and increased permeability and changes in the expression of tight junction proteins.

[Development of the Core Occupational Stress Scale for occupational populations in China].

Objective: To develop the Core Occupational Stress Scale (COSS) for key occupational populations, and to assess the reliability and validity of COSS in China. Methods: According to the literature review, in-depth interview and expert evaluation, the item pool of COSS was established. A total of 20 981 employees (3 703 employees from 2018 and 17 178 employees from 2019) of manufacturing, medical, and traffic polices, etc. from Beijing, Tianjin, Shanghai, Chongqing, Jiangsu, Shandong, Zhejiang, Hunan, Guangdong and Hubei were investigated using convenient sampling of those participating in general or occupational health examination of the day. Item differential test and exploratory factor analysis (EFA) were used to screen items from the item pool; confirmatory factor analysis (CFA) was used to test structure validity; criterion and convergent validity were tested by Pearson correlation. Cronbach's α coefficient was used to test the reliability of the scale. Results: The EFA suggested a four-factor structure for a 17-item version of COSS, which were social support, organization and reward, demand and effort, and control. It explained 62.06% of the total variance and factor loadings ranged from 0.447 to 0.918. The CFA confirmed the hypothesized four-factor model (GFI=0.904, CFI=0.912, RMSEA=0.079). The COSS scores were positively correlated with burnout, depressive symptoms, and effort-reward imbalance scores with r ranging from 0.357 to 0.567 (P<0.05). The total COSS and each dimension of Cronbach's α coefficients were 0.772-0.896. Conclusions: The COSS has good reliability and validity and can be used as an occupation stress assessment for occupational populations in China.

[A preliminary study on establishment of the Core Occupational Stress Scale (COSS) norms for manufacturing and medical workers in China].

Objective: To establish the Core Occupational Stress Scale (COSS) norm values for manufacturing and medical workers. Methods: A total of 10 316 manufacturing workers of 20 companies from 7 provincial capital cities and 5 031 medical workers of 19 hospitals from 4 provincial capital cities were investigated using a stratified sampling method. Questionnaire information including occupational stress was collected. Norms of mean, percentile and T scores were calculated for COSS total and sub-dimension scores by different demographic characteristics. Based on the normal distribution, cut points of x¯+0.5s, x¯+s, x¯+1.5s of COSS total scores were calculated to classify the degree of occupational stress. Results: The COSS total scores were (45.48±8.16) and (45.71±8.46). The 50th percentiles were both 46, and T score ranges were (15-92) and (16-91), respectively, for manufacturing and medical workers. When the total score was<50, 50-53, 54-57, and >57 for manufacturing worker, or<50, 50-54, 55-58, and >58 for medical workers, occupational stress would be classified into none, mild, moderate, and severe levels. Conclusion: Compatible with the national condition of China, as well as the principles of psychological measurement, these norm values for manufacturing and medical workers could provide theoretical support and practical guideline on occupational mental health promotion.

[The mediating role of psychological capital between occupational stress and suicidal ideation].

Objective: To analyze the mediating effect of psychological capital (PsyCap) between occupational stress and suicidal ideation. Methods: In September 2017, stratified-cluster sampling method was adopted to select employees of an electronic manufacturing service industry as respondents for a questionnaire survey in Jiangsu province. The demographic characteristics of employees were collected. A total of 2 465 employees were investigated, and 2 216 valid questionnaires were collected. The level of occupational stress and PsyCap was assessed by the Effort-Reward Imbalance Scale(ERI)and PsyCap Questionnaire. Results: The age of 2 216 employees was (28.70±5.26) years old, including 1 230 males (55.5%). The scores of occupational stress on effort, reward and over-commitment were (3.08±0.63), (3.73±0.60) and (2.51±0.68), respectively. The average ERI index (ratio of effort to return) was (0.88±0.39). The total score of PsyCap was (86.62±15.23). The detection rate of suicidal ideation within two weeks was 13.9% (309/2 216). The average score of effort and over-commitment and the ERI index were positively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about 0.081, 0.141 and 0.164, respectively. The average score of reward and total score of PsyCap were negatively correlated with the number of suicidal ideation detected within two weeks, with correlation coefficients about -0.206 and -0.228, respectively. The mediating effect results showed that PsyCap had mediating effect on the effort, reward, over-commitment and suicidal ideation of occupational stress respectively, with mediating effect values of -0.087 (95%CI: -0.018,-0.019), -0.299 (95%CI: -0.428,-0.200) and 0.096 (95%CI: 0.0394, -0.170). The mediating effect percentages were 9.43%, 17.92%, and 9.54%, respectively. Conclusion: PsyCap has a mediating effect between effort, reward, over-commitment of occupational stress and suicidal ideation.

[Feasibility of evaluating the left ventricular function in patients with cardiovascular diseases by fully automatic quantified three-dimensional transthoracic echocardiography].

Objective: To investigate the clinical value of left ventricular function assessment in patients with cardiovascular disease by fully automatic quantified three-dimensional transthoracic echocardiography. Methods: One hundred and ninety-seven patients with cardiac diseases were examined by three-dimensional transthoracic echocardiography from September 2017 to May 2019. Data from 61 patients with grade 1 echocardiographic image quality were used to determine the default boundary values of endocardial end-diastolic and end-systolic phases. Clinical features were analyzed based on electronic medical records. The accuracy and repeatability of this strategy was evaluated by comparing left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) measured by automated quantitative three-dimensional echocardiography and those measured by conventional manual transthoracic echocardiography, the latter served as gold standard. Results: The levels of LVEDV, LVESV and LVEF measured by automatic three-dimensional echocardiography were positively correlated with values obtained by manual measurement（r=0.97，0.97, 0.98, 0.97, 0.97, 0.96；P<0.05). The levels of LVEDV and LVESV measured by full-automatic three-dimensional echocardiography were significantly higher than those obtained by manual three-dimensional echocardiography（all P<0.05）. The classification and correlation of systolic dysfunction in patients with abnormal ventricular wall motion by automatic three-dimensional echocardiography were significantly improved after manual calibration (κ=0.74, P=0.00) as compared to without manual calibration (κ=0.63, P=0.00). The inter-observer and intra-observer variability of fully automated three-dimensional echocardiography were significantly smaller than manual three-dimensional echocardiography（both P<0.05）. Conclusion: Fully automatic quantified three-dimensional transthoracic echocardiography possesses excellent accuracy and repeatability in measuring left ventricular volume and function， and it is feasible for clinical application.

Circle RNA FOXP1 promotes cell proliferation in lung cancer by regulating miR-185-5p/Wnt1 signaling pathway.

OBJECTIVE: It is reported that circular RNA plays an important role in various cancers in recent years. However, there is less investigation reported in lung adenocarcinoma (LUAD) about circRNA. This study aims to explore the role and molecular mechanism of circle RNA FOXP1 in LUAD procession. PATIENTS AND METHODS: The levels of circFOXP1 and miR-185-5p in LUAD cell lines and LUAD cancer samples were examined by RT-PCR. The functions of circFOXP1 and miR-185-5p at LUAD cells were detected by cell transfection of the overexpression or repression. The A549 and H1299 cell proliferation were detected by MTT assay and colony formation assay. And the cell apoptosis was detected by TUNEL assay. The expression levels WNT1 were measured by Western blot in A549 and H1299 cells. Furthermore, the luciferase assay detected the direct interaction between circFOXP1 and miR-185-5p or miR-185-5p and WNT1. RESULTS: The circFOXP1 expression was increased in LUAD patients and LUAD cell lines. The downregulation of circFOXP1 significantly repressed LUAD cell proliferation and promoted cell apoptosis. Moreover, the luciferase assay results confirmed that circFOXP1 directly interacted with miR-185-5p. Overexpression of miR-185-5p could reverse the effect of circFOXP1 in LUAD cell. Besides, the luciferase results showed that miR-185-5p directly interacted with WNT1. miR-185-5p overexpression inhibited the WNT1 expression, while circFOXP1 repression decreased the WNT1 level in LUAD cell lines. The downregulating WNT1 could reverse the effects of miR-185-5p inhibition in LUAD cell lines. Furthermore, WNT1 was significantly upregulated in LUAD cancer tissues. In addition, circFOXP1 level was negatively correlated with miR-185-5p expression and positively correlated with WNT1 expression in LUAD cancer tissues. CONCLUSIONS: These data suggested that circFOXP1 promoted cell proliferation and repressed cell apoptosis in LUAD by regulating miR-185-5p/WNT1 signaling pathway. It provides a novel potential therapeutic agent for the treatment of LUAD.

[Lymphocyte activation gene 3 expression on T lymphocyte cell subsets in patients with myelodysplastic syndrome].

Objective: To investigate the expression of Lymphocyte activation gene 3 (LAG3) in myelodysplastic syndromes (MDS) patients. Methods: A total of 16 MDS patients newly diagnosed in Hematology Department of Tianjin Medical University were enrolled from January to November 2019. The healthy control (HC) group includes 16 cases of healthy adults. The expression levels of LAG3 on CD8(+)T cells, CD4(+)T cells and regulatory T cells (Treg) in MDS patients and healthy controls were detected by flow cytometry. Results: A total of 16 patients with MDS were included, including 5 males and 11 females, with a median age of 56 (18-80) years old. HC group includes 16 healthy adults, 8 men and 8 women, with a median age of 40 (17-69) years. There was no statistically significant difference in gender and age composition between the two groups (both P>0.05). The expression of LAG3 on CD8(+)T cells in MDS patients (74.45%±22.31%) was significantly higher than that in HC group (58.78%±14.82%, P<0.05). The LAG3 expression on Treg in MDS patients (64.91%±10.32%) were significantly higher than that of HC group (49.09%±13.58%, P<0.05). There was no statistical difference in LAG3 expression on CD4(+)T cells between the two groups. Conclusion: The expression of LAG3 on CD8(+)T cells and Treg increases in MDS patients than that of healthy people.

Kallistatin alleviates heart failure in rats by inhibiting myocardial inflammation and apoptosis via regulating sirt1.

OBJECTIVE: Heart failure (HF) is the loss of myocardial structure and function caused by various congenital or acquired heart diseases. This study explored the new target of treatment of HF by investigating the effect of Kallistatin (KS) on inflammation and apoptosis of myocardial tissue in HF rats. MATERIALS AND METHODS: We used doxorubicin to induce rat HF, and determined the success rate of modeling by detecting changes in rat heart weight and body weight, cardiac function and histology. We used two different doses (1 mg/kg, 2 mg/kg) of KS intraperitoneally injected rats and detected changes in inflammation and apoptosis of rat myocardial tissue by enzyme-linked immunosorbent assay (ELISA), Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining. Changes in the expression of sirt1 were also detected. In addition, we cultured rat myocardial cell line, H9c2 cells, and used siRNA-sirt1 to inhibit sirt1 in H9c2 cells to clarify the mechanism of KS regulating myocardial cells. RESULTS: The body weight of HF rats treated with KS decreased while the heart weight increased. KS has also been found to reduce the concentration of brain natriuretic polypeptide (BNP) in rat serum. The results of echocardiography showed that KS effectively relieved the cardiac function of HF rats. Inflammatory factors (interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor (TNF)-α) and pro-apoptotic molecules (caspase3/9 and Bax) in the serum and myocardial tissue of rats treated with KS were also significantly reduced. The inhibition of sirt1 in H9c2 cells significantly reduced the anti-apoptotic effect of KS on H9c2 cells. CONCLUSIONS: KS reduces the inflammation and apoptosis of myocardial tissue in HF rats by promoting the expression of sirt1, thereby alleviating HF-induced myocardial injury.

Effects of miR-32 targeting PTEN on proliferation and apoptosis of myeloma cells.

OBJECTIVE: To explore the effects of micro ribonucleic acid (miR)-32 on the proliferation and apoptosis of myeloma cells, and to verify whether it exerts its function by targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN). PATIENTS AND METHODS: The differentially expressed miRNAs were screened in healthy people and myeloma patients. The myeloma U266 cells transfected with negative control (NC) were used as control group, those transfected with miR-32 inhibitor as transfection group, and those transfected with miR-32 inhibitor and treated with PTEN inhibitor SF1670 as the transfection + inhibitor group. Then, the cell proliferation and apoptosis in each group were detected using the 5-Ethynyl-2'-deoxyuridine (EdU) kit and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Finally, the expressions of apoptosis-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2 homologous antagonist/killer (Bak), caspase-9, and survivin were detected. RESULTS: The expressions of some miRNAs and genes in myeloma patients were significantly different from those in healthy people. In myeloma patients, miR-32, miR-126, miR-123, and miR-183 were significantly highly expressed, while miR-5, miR-76, and miR-50 were remarkably lowly expressed. After myeloma U266 cells were transfected with the miR-32 inhibitor, the expression of miR-32 markedly declined. In addition, the mRNA expression of PTEN in myeloma cells rose after transfection with the miR-32 inhibitor, and declined after addition of the PTEN inhibitor SF1670, which were consistent with the results of Western blotting. Besides, the proliferation ability of myeloma cells was evidently weakened after transfection with the miR-32 inhibitor, while it was restored to a certain extent after addition of the PTEN inhibitor SF1670. Moreover, the number of apoptotic myeloma cells was remarkably larger after transfection with the miR-32 inhibitor, while it was remarkably smaller after addition of the PTEN inhibitor SF1670. The expressions of pro-apoptotic proteins Bak and caspase-9 in myeloma cells were significantly increased after transfection with the miR-32 inhibitor (p<0.05), and significantly decreased after addition of the PTEN inhibitor SF1670, while the expressions of anti-apoptotic proteins Bcl-2 and survivin were opposite to those of Bak and caspase-9. CONCLUSIONS: MiR-32 targeting PTEN will have certain effects on the proliferation and apoptosis of myeloma cells.