Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

OBJECTIVE: To study the mechanism of the anti-tumor effect of Morinda citrifolia (noni). METHODS: The influences of noni juice on cell proliferation, apoptosis, invasion, migration and the activity of AKT/nuclear factor- κ B (NF- κ B) signaling pathway in A549 human lung cancer cells were detected by MTT, cell counting kit-8, colony formation, Annexin V/PI double labeling, transwell, scratch test and immunoblotting assay, respectively. A549 cells were inoculated into the right axilla of nude mice, followed by noni juice treatment. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell proliferation and expression of apoptosis-related proteins were measured by immunohistochemistry, and the activity of NF- κ B signaling pathway was measured by immunoblotting. RESULTS: The in vitro studies showed that noni juice inhibited the A549 cells proliferation, migration and invasion. Noni juice also promoted cells apoptosis in A549 cells. Immunoblotting assay showed that the phosphorylation level of AKT, p50, and STAT3 proteins was inhibited to different extents after noni juice treatment. The in vivo studies showed that noni juice effectively suppressed tumor formation of A549 cells in nude mice. Noni juice treatment inhibited the expression of Ki67, PCNA, and Bcl-2 protein in the tumor; while promoted the expression of caspase-3 protein. Additionally, we also found that noni juice treatment could restrain the activity of AKT/NF- κ B signaling pathway in the tumor tissue. CONCLUSION Noni juice inhibited the proliferation of A549 lung cancer cells, induced apoptosis, and inhibited cell invasion and migration via regulating AKT/NF- κ B signaling pathway.

OBJECTIVE: To investigate the clinical characteristics, laboratorial and bone marrow pathological features of primary thrombocytopenia (ET) patients with different mutations of CALR, JAK2 and MPL genes. METHODS: The chinical data of 120 cases of ET in Jiangsu provincial people's hospital/ The First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2017 were collected and analyzed, including 76 cases with JAK2 gene mutation, 40 cases with CALR gene mutation, 2 cases with MPL gene mutations, 2 cases without gene mutation. RESULTS: Among the ET patients, compared with the JAK2 gene mutation, CALR gene mutation showed statistically significant deareament of white blood cells and hemoglobin (P=0.001, P=0.01) and the male platelets in CALR group showed significant increament (P=0.04). Fourthermore, the average number of megakaryocytes and its cluster numbers in each hight power field of vision showed statistically significant decreament in CALR group as compared with JAK2 group (P=0.001, P=0.001), and thrombotic events in CALR group were signicantly lower than those in JAK2 group (7.5% vs 18.4%) (P=0.03). CONCLUSION Mutations of CALR, JAK2 have different clinical characteristics and blood pathological changes of Chinese ET patients, and their clinical significance is worth to explore.
Bone Marrow ; Calreticulin ; genetics ; China ; Humans ; Janus Kinase 2 ; genetics ; Male ; Mutation ; Receptors, Thrombopoietin ; genetics ; Thrombocythemia, Essential

Objective: To study the correlation between the content changes of main medicinal ingredients and the color values of Rhei Radix et Rhizoma during storage based on the principle of chromaticity analysis,and to provide reference for studying on the mechanism of discoloration and improving the quality evaluation of Rhei Radix et Rhizoma. Method: Simulated accelerated test was adopted in this study, where Rhei Radix et Rhizoma was stored under high temperature(40±5)℃,high humidity RH(92.5±5)%and strong light(4 000±500)Lx conditions to accelerate its discoloration. For the samples taken at different time points,the color value was determined by spectrophotometer and the total contents of anthraquinone and free anthraquinones,sennoside A,B,catechin and gallic acid were determined by high performance liquid chromatography (HPLC). The correlation between the effective components and the color value of rhubarb was analyzed by SPSS software. Result: During the storage process,it was observed by the eye that the color of Rhei Radix et Rhizoma was significantly darker and darker in the simulated acceleration test. According to the analysis of the chromaticity value results,the changes of chromaticity values L^*and E^*ab of Rhei Radix et Rhizoma were significantly negatively correlated with free strontium content(P<0.05),and significantly positively correlated with catechin content(P<0.05),but there was no correlation with total anthraquinones and sennoside A. The chromaticity value a^* was significantly negatively correlated with gallic acid(P<0.05) and significantly positively correlated with sennoside B(P<0.05). Conclusion: There is a certain correlation between the change of color value and the content of six medicinal ingredients during Rhei Radix et Rhizoma storage.

Objective: To observe the effect of modified Chaihu Shugantang on the expression of miRNA-204 in hippocampus of epileptic mice, and to explore its mechanism of neuroprotection. Method: The sixty mice were randomly divided into 6 groups:normal group, model group (pilocarpine 180 mg·kg^-1), and modified Chaihu Shugantang group (7 g·kg^-1·d^-1), modified Chaihu Shugantang+miRNA-204 mimic group (7 g·kg^-1·d^-1+ 2 μL), modified Chaihu Shugantang+miRNA-204 inhibitor group (7 g·kg^-1·d^-1+2 μL), carbamazepine group (30 mg·kg^-1·d^-1),each was given intragastric administration for 2 weeks,using pilocarpine to cause epilepsy in mice, respectively, add flavor to Bupleurum after intragastric administration, inhibition and overexpression of miRNA-204, the mice were sacrificed and their hippocampus tissues were harvested.The indicators of each group were observed, Real-time quantitative PCR detecting system (Real-time PCR) was used to detect mouse hippocampal miRNA-204 expression, Western blot analysis of autophagy-related protein microtubule-associated protein light chain 3 (LC3), autophagy-associated marker protein 7 (ATG7) expression, hematoxylin pathological condition of hippocampus in each group was observed by hematoxylin-eosin(HE)staining.The autophagy of hippocampus in each group was observed by transmission electron microscopy. Result: Compared with normal group, the expression of miRNA-204 was significantly decreased in model group (P<0.01), the pathological changes in the hippocampal C1 area were the most obvious, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was increased (P<0.01), and the autophagy was small. Compared with model group, the expression of miRNA-204 in the hippocampus of the modified Chaihu Shugantang group was increased (P<0.05), the pathological changes in the hippocampal C1 area were alleviated, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was decreased (P<0.05), and the autophagy was small. The number of body decreased,the expression of miRNA-204 in hippocampus of modified Chaihu Shugantang+miRNA-204 mimic group was significantly increased (P<0.01), the pathological changes in hippocampal C1 area were the lightest, and the expression of ATG7, LC3Ⅱ/LC3I was decreased (P<0.01), the number of autophagosomes was the least.Compared with modified Chaihu Shugantang group, the above-mentioned indicators of modified Chaihu Shugantang+miRNA-204 inhibitor group had the same change trend and the change range decreased (P<0.05). Conclusion: Modified Chaihu Shugantang can improve the pathological changes of hippocampus in mice with epilepsy and play a neuroprotective role. The mechanism may be to increase the expression of miRNA-204 in hippocampus of mice with epilepsy, inhibit excessive autophagy of neurons and reduce apoptosis.

Background: Studies have reported mitophagy activation in renal tubular epithelial cells (RTECs) in acute kidney injury (AKI). Phosphatase and tensin homolog-induced putative kinase 1 (PINK1) and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation; however, little is known about the role of PINK1-Parkin mitophagy in septic AKI. Here we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in vivo. Methods: Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide (LPS) and in RTECs from septic AKI rats induced by cecal ligation and perforation (CLP). Autophagy-related ultrastructural features in rat RTECs were observed using electron microscopy. Gain- and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell mitophagy. Autophagy activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in vivo. Results: LPS stimulation could significantly induce LC3-II and BECN-1 protein expression (LC3-II: 1.72 ± 0.05 vs. 1.00 ± 0.05, P < 0.05; BECN-1: 5.33 ± 0.57 vs. 1.00 ± 0.14, P < 0.05) at 4 h in vitro. Similarly, LC3-II, and BECN-1 protein levels were significantly increased and peaked at 2 h after CLP (LC3-II: 3.33 ± 0.12 vs. 1.03 ± 0.15, P < 0.05; BECN-1: 1.57 ± 0.26 vs. 1.02 ± 0.11, P < 0.05) in vivo compared with those after sham operation. Mitochondrial deformation and mitolysosome-mediated mitochondria clearance were observed in RTECs from septic rats. PINK1 knockdown significantly attenuated LC3-II protein expression (1.35 ± 0.21 vs. 2.38 ± 0.22, P < 0.05), whereas PINK1 overexpression markedly enhanced LC3-II protein expression (2.07 ± 0.21 vs. 1.29 ± 0.19, P < 0.05) compared with LPS-stimulated HK-2 cells. LPS-induced proapoptotic protein expression remained unchanged in autophagy activator-treated HK-2 cells and was significantly attenuated in PINK1-overexpressing cells, but was remarkably upregulated in autophagy inhibitor-treated and in PINK1-depleted cells. Consistent results were observed in flow cytometric apoptosis assay and in renal function indicators in rats. Conclusion PINK1-Parkin-mediated mitophagy might play a protective role in septic AKI, serving as a potential therapeutic target for septic AKI.

OBJECTIVE: To study the clinical efficacy of interactive group sandplay versus individual sandplay in the treatment of preschool children with autism spectrum disorder (ASD). METHODS: A total of 80 ASD children, aged 4-6 years, were enrolled and randomly divided into experimental and control groups, with 40 children in each group. The children in the experimental group joined group sandplay with normal children at a ratio of 1: 3, and those in the control group were treated with individual sandplay. The Aberrant Behavior Checklist (ABC) and Autism Treatment Evaluation Checklist (ATEC) were used to evaluate the treatment outcome after three months of intervention. RESULTS: There were 33 children in the experimental group and 28 in the control group. After three months of intervention, the experimental group had significant reductions in the scores of irritability, social withdrawal, and stereotypic behavior and the total score of the ABC scale (P<0.05), and the control group had significant reductions in the scores of behavior and inappropriate speech and the total score of the ABC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the score of social withdrawal and the total score of the ABC scale after three months of intervention (P<0.05). After three months of intervention, the experimental group had significant reductions in the scores of sociability, sensory and cognitive awareness, and physical/health behavior and the total score of the ATEC scale (P<0.05), and the control group had significant reductions in the scores of speech, sociability, and physical/health behavior and the total score of the ATEC scale (P<0.05). Compared with the control group, the experimental group had significantly greater improvements in the scores of speech, sociability, and sensory and cognitive awareness and the total score of the ATEC scale after intervention (P<0.01). Compared with the control group, the experimental group also had significantly greater improvements in eye contact and sand stereotyped arrangement (P<0.05). CONCLUSIONS Both interactive group sandplay and individual sandplay are effective in the treatment of ASD in preschool children. Interactive group sandplay is better than individual sandplay in the treatment of ASD, with significant improvements in sociability, emotion and stereotypic behavior.
Autism Spectrum Disorder ; therapy ; Child ; Child, Preschool ; Emotions ; Humans ; Play Therapy ; Treatment Outcome

AIM To study the chemical constituents from the roots tuber of Aconitum ouvrardianum H..METHODS The ethyl acetate fraction of methy extract from A.ouvrardianum roots tuber was isolated and purified by silica,aluminium oxide column,Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Eighteen compounds were isolated and identified as kongboendine (1),anisoezochasmaconitine (2),lipo-14-O-anisoylbikhaconine (3),franchetine (4),talatisamine (5),chasmanine (6),crassicauline A (7),chasmaconitine (8),14-dehydrotalatisamine (9),lipoindaconitine (10),indaconitine (11),yunaconitine (12),lipoyunaconitine (13),liljestrandisine (14),transconitine B (15),ouvrardiantine (16),atropurpursine (17),8-deacetylyunaconitine (18).CONCLUSION Compounds 1-4,9-10,13,15,17 are isolated from this plant for the first time.

Objective To investigate the status of psychological quality of college students ' innovation and entrepreneurship, identify the elements of the psychological quality and problems and countermeasures against the psychological quality training in medical schools. Methods A questionair was made and administered to Kunming Medical University students and Chi-square analysis was used to analyze the gender, major, grade, and entrepreneurial intention differences between different groups of students so as to analyze the psychological factors affecting College students ' undertaking intention. Results A total of 1150 questionnaires,1099 was recovered,the effective recovery rate was 95.6％. Psychological quality score was (76.9 ±9.0), good mental qualities only was 8.2％, entrepreneurial environment, factors of psychological quality of good-willed persons were only 0.5％and 15.5％. Female entrepreneurial intentions were better than those of men (<0.001) . Science students' undertaking intention was superior to liberal arts students ( =0.025), knowledge of entrepreneurship difference between knowledge of business groups and <0.005,there was a statistically significant difference, about the environment worse group entrepreneurial intention superior knowledge of business groups. Conclusions As students' psychological qualities are poor,have poor psychological quality,in teaching we should strengthen the cultivation of medical students' entrepreneurial ability and correct understanding of entrepreneurship, create a good business environment, increase the entrepreneurship policy advocacy efforts, and create a good business environment and atmosphere so as to strengthen the entrepreneurship education, improve entrepreneurship courses so that students fully understand the cognitive and psychological qualities, stimulate the entrepreneurial motivation, lay the Foundation for entrepreneurship.