Depression and insomnia are intimately related. Depressed patients usually manifest sleep discontinuity and early awakening, reduced or no slow wave sleep (SWS) and shortened latency of rapid eye movement (REM) sleep. These sleep abnormalities are very similar to those caused by over activated hypothalamic-pituitary-adrenal (HPA) axis with stress. Therefore, the animal models developed by post-traumatic stress disorder or chronic unpredictable mild stress could be used to evaluate drugs which have effects of both anti-depression and improvement of sleep quality, and to provide a more reliable platform for further studis on the mechanisms of depression and accompanied insomnia. This review mainly focuses on the typical features of sleep disturbance of depression, possible pathophysiological mechanisms, establishment of animal stress models and analysis of their abnormal sleep characteristics.

Objective To investigate the epidemiological characteristics of an outbreak of respiratory tract infection caused by human rhinovirus （HRV） in a school in Nanxun District of Huzhou City， and provide scientific evidence for prevention and control of outbreaks of upper respiratory tract infection caused by HRV in the future. Methods The investigation was performed according to the Guidelines for Response to Outbreaks of Influenza-like Illness （2018 version）. It mainly referred to the records of nonattendance due to illness， morning and afternoon examination， and hospital treatment records， to search for cases. Then CDC staffs carried out epidemiological investigation on cases， interviewed the head teacher， and inspected the site. Throat swabs were collected for detection of SARS-CoV-2 and subsequently 14 common viruses that may cause upper respiratory tract infection. Results A total of 68 cases with HRV infection were identified. The first case and last case occurred on May 20 and 30， respectively. After a 3-day longest incubation period， there was no emerging case， suggesting the end of the outbreak. The incidence was 25.00% （11/44） in Class 101， 30.23% （13/43） in Class 109， 25.58% （11/43） in Class 110， 35.26% （16/45） in Class 211， and 39.96% （17/46） in Class 307. There was no significant difference in the incidence among classes （ χ ²=1.67， P >0.05）. The patients aged from 7 to 9 years. The incidence was 27.19% （31 / 114） in male and 34.58% （37/107） in female， with no significant difference （ χ ²=1.41， P >0.05）. The symptoms were mild， with no hospitalization， severe illness or death. The patients had mainly cough （100.00%）， sore throat （61.76%）， and runny nose （47.06%）， whereas had little muscle soreness （4.41%）. Of the patients， 69.12% visited hospitals， 23.53% took medicine by themselves， while 7.35% did not seek any medical treatment or medicine. Throat swabs were collected from 22 cases， testing negative for SARS-CoV-2. Then 14 common respiratory viruses were examined， of which HRV was positive in 16 cases. Conclusion Children with HRV infection have milder symptoms compared to influenza infection， which is difficult to be noticed by school teachers and parents. Students should maintain personal hygiene and develop health habits. Moreover， schools should strength relevant health education， implement morning and afternoon health inspection， and prevent students with illness to routinely go to schools.

Objective:To analyse the risk factors of postpartum hemorrhage in vaginal delivery patients with low-lying placenta.Methods:We retrospectively evaluated the data from January 2014 to December 2015 of 345 cases of vaginal delivery pregnant women with low-lying placenta.According to postpartum hemorrhage,the data were divided into two groups:single factor analysis and multivariate logister regression analysis were used to assess the risk factors.Results:Postpartum hemorrhage in 47 cases,the total rate is 13.6％.Univariate analysis showed that assisted reproductive conception,history of prenatal hemorrhage,placenta from the cervix within the distance ≤ 10 mm,placental adhesions were more prone to postpartum hemorrhage(P ＜ 0.05).Logistic multivariate regression analysis showed that assisted reproductive conception (OR =8.181,95％ CI 3.072-21.791) and placental adhesions(OR=6.543,95％ CI 3.107-13.775) were independent risk factors for postpartum hemorrhage.Conclusions:Systematic prenatal care,carefully transvaginal ultrasound examination before labor and evaluation of these risk factors,may be able to provide a better choice of mode of delivery to low-lying placenta patients and predict postpartum hemorrhage risk,thereby reducing its postpartum hemorrhage rate.

This research focuses on the application of multiple interactive modes in online teaching, combined with the actual teaching cases of the anesthesia equipment course of Xiangya Anesthesiology Specialty of Central South University, showing in detail the preparations for interactive teaching before anesthesia equipment learning, the interaction in online classrooms, the extension of interactive teaching outside the classroom, and the evaluation of interactive teaching feedback mechanism throughout the implementation process. By establishing a "host-guest-viewer" mode, the effect of online live broadcasting is maximized. Through the 360-degree materialized explanation with students as the main body, we will make opening in the pain points and blocking points of online teaching in which students do not go to class and students have no thinking, and promote the improvement of online teaching quality and efficiency. In the following practice, we must continue to work on issues such as the improvement of teacher talent quality, the building of an efficient talent team, and the construction of practical application value evaluation systems for teaching.

Objective To investigate the effect of cognitive behavior therapy (CBT) on the conversion of individuals with ultra-high-risk (UHR) of schizophrenia,and to find out the related influence factors.Methods Patients were randomly divided into study group (50 cases) and control group (49 cases) by the digital random table method.The study group received cognitive behavioral therapy,and the control group only got follow-up questionnaire.Structured Interview for Prodromal Syndromes (SIPS) was used to evaluate psychosis risk symptoms of each UHR individuals at baseline,3 months,6 months,12 months and 18 months respectively and the effects of CBT on conversion and related influencing factors were analyzed.Results There was no significant difference in the conversion rate (P＞ 0.05) between study group and control group after 3 months,but the conversion rate of study group was significantly lower than the control group after 6 months(6.00％ vs 20.41％,P＜0.05),12 months(10.00％ vs 24.49％,P＜0.05)and 18 months(10.00％ vs 28.57％,P＜0.05).CBT could effectively improve conditions for individuals with positive symptom (study group:5.30±3.62,5.04±3.89,4.38±4.13,5.26±3.65,5.94±4.19,control group:5.59±3.62,6.33±5.29,6.98 ±4.96,7.02±5.02,8.39±6.42,F=4.326,P=0.000) of UHR,but the improvement was not significant for negative individuals (F=1.555,P=0.215).CBT could be effective for disorganized symptom (F=6.901,P =0.010) and general symptom (F=7.752,P=0.006) as well.The poor family relationship was the risk factor of conversion to the schizophrenia (OR=3.411,95％CI=1.016-11.453,P=0.047).Conclusion CBT can effectively reduce the conversion rate of UHR individuals.CBT has a good remission effect on the positive symptoms,disintegrating symptoms and general symptoms of UHR.Family relationship affects prognosis of UHR individuals.

Objective:To explore the predictive value of high frequency ultrasound and contrast-enhanced imaging features in predicting cervical lymph node metastasis of papillary thyroid microcarcinoma (PTMC).Methods:A retrospective analysis of 184 patients with PTMC confirmed by surgery and pathology in the First Hospital of Shanxi Medical University from March 2015 to December 2018 was performed. According to the presence or absence of lymph node metastasis, the patients were divided into metastasis group and non-metastasis group. Univariate analysis was used to compare the features of high frequency ultrasound and contrast-enhanced ultrasound in the two groups, and multivariate regression analysis was used to determine the independent risk factors of cervical lymph node metastasis, and their prediction value was analyzed with ROC curves.Results:Among 184 patients, 50 (27.2%) had lymph node metastasis. Univariate analysis showed that age (χ 2=10.026) , number of nodules (χ 2=10.497) , calcification (χ 2=17.414) , aspect ratio (χ 2=4.564) , nodule location (χ 2=20.542) , enhancement time (χ 2=7.882) , enhancement mode (χ 2=6.416) and enhancement intensity (χ 2=9.899) were significantly associated with cervical lymph mode metastasis (all P<0.05). Multivariate analysis showed that age<45 years old ( OR=2.626, 95 %CI:1.141-6.052) , multifocal lesions ( OR=3.648, 95 %CI:1.542-8.631) , microcalcification ( OR=2.925, 95 %CI:1.055-8.115) and equal/high enhancement ( OR=8.042, 95 %CI: 1.879-34.429) were independent risk factors for lymph node metastasis ( P<0.05). The area under the ROC curve of above indicators combined was 0.762. Conclusions:High frequency ultrasonography combined with contrast-enhanced imaging can provide useful information for predicting cervical lymph node metastasis of PTMC. For PTMC patients aged<45 years with multifocal lesions, microcalcification and equal/high enhancement, the risk of cervical lymph node metastasis is significantly increased.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Plant fungal pathogens secrete numerous proteins into the apoplast at the plant-fungus contact sites to facilitate colonization.However,only a few secretory proteins were functionally characterized in Magnaporthe oryzae,the fungal pathogen causing rice blast disease worldwide.Asparagine-linked glycosylation 3(Alg3)is an a-l,3-mannosyltransferase functioning in the N-glycan synthesis of N-glycosylated secretory proteins.Fungal pathogenicity and cell wall integrity are impaired in Aalg3 mutants,but the secreted proteins affected in Aalg3 mutants are largely unknown.In this study,we compared the secretomes of the wild-type strain and the Aalg3 mutant and identified 51 proteins that require Alg3 for proper secretion.These proteins were predicted to be involved in metabolic processes,interspecies interactions,cell wall organization,and response to chemicals.Nine proteins were selected for further validation.We found that these proteins were localized at the apoplastic region surrounding the fungal infection hyphae.Moreover,the N-glycosylation of these proteins was significantly changed in the Aalg3 mutant,leading to the decreased protein secretion and abnormal protein localization.Furthermore,we tested the biological functions of two genes,INV1(encoding invertase 1,a secreted invertase)and AMCase(encoding acid mammalian chinitase,a secreted chitinase).The fungal virulence was significantly reduced,and the cell wall integrity was altered in the Ainv1 and Aamcase mutant strains.Moreover,the N-glycosylation was essential for the function and secretion of AMCase.Taken together,our study provides new insight into the role of N-glycosylated secretory proteins in fungal virulence and cell wall integrity.

Objective To establish interferon-induced transmembrane protein 3(Ifitm3)knockout mice and to explore the effects of Ifitm3 on the proliferation and differentiation of adult neural stem cells of mice(aNSCs).Methods IFITM3 knockout mice were established by the CRISPR/Cas9 method and identified by genotype identification and Western Blot.The differences between Ifitm3-knockout mice and wild-type mice were analyzed by hematoxylin-eosin(HE)staining and flow cytometry.The aNSCs of wild-type mice and Ifitm3-knockout mice were isolated and cultured,the number and size of neurospheres were detected,The ability of aNSCs to proliferate and differentiate were detected by quantitative reverse-transcription polymerase chain reaction,Western Blot,and immunofluorescence.Results Ifitm3-knockout mice were successfully established.The mice developed normally,and there were no obvious abnormalities either histopathologically or the immune system.In vitro experiments showed that Ifitm3 knockout inhibited the self-renewal potential of aNSCs,led to a decrease in the proliferation ability of aNSCs,and inhibited the differentiation of aNSCs into immature neurons and astrocytes.Conclusions This study finds that a lack of IFITM3 result in the ability of aNSCs to proliferate and differentiate decreased,IFITM3 may regulate the function of aNSCs.

BACKGROUNDThe initial osteoblastic adhesion to materials characterizes the first phase of cell-material interactions and influences all the events leading to the formation of new bone. In a previous work, we developed a novel amorphous calcium phosphate (ACP)/poly(L-lactic acid) (PLLA) material that demonstrated morphologic variations in its microstructure. The aim of this study was to investigate the initial interaction between this material and osteoblastic cells. Cellular attachment and the corresponding signal transduction pathways were investigated.

METHODSA porous ACP/PLLA composite and PLLA scaffold (as a control) were incubated in fetal bovine serum (FBS) containing phosphate-buffered saline (PBS), and the protein adsorption was determined. Osteoblastic MG63 cells were seeded on the materials and cultured for 1, 4, 8, or 24 hours. Cell attachment was evaluated using the MTS method. Cell morphology was examined using scanning electron microscopy (SEM). The expression levels of the genes encoding integrin subunits α1, α5, αv, β1, focal adhesion kinase (FAK), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using real-time reverse transcription polymerase chain reaction (RT-PCR).

RESULTSThe ACP/PLLA material significantly increased the protein adsorption by 6.4-fold at 1 hour and 2.4-fold at 24 hours, compared with the pure PLLA scaffold. The attachment of osteoblastic cells to the ACP/PLLA was significantly higher than that on the PLLA scaffold. The SEM observation revealed a polygonal spread shape of cells on the ACP/ PLLA, with the filopodia adhered to the scaffold surface. In contrast, the cells on the PLLA scaffold exhibited a spherical or polygonal morphology. Additionally, real-time RT-PCR showed that the genes encoding the integrin subunits α1, αv, β1, and FAK were expressed at higher levels on the ACP/PLLA composite.

CONCLUSIONSThe ACP/PLLA composite promoted protein adsorption and osteoblastic adhesion. The enhanced cell adhesion may be mediated by the binding of integrin subunits α1, αv, and β1, and subsequently may be regulated through the FAK signal transduction pathways.

Biocompatible Materials ; chemistry ; Calcium Phosphates ; chemistry ; Cell Adhesion ; physiology ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; metabolism ; Humans ; Integrin alpha1 ; metabolism ; Integrin alpha5 ; metabolism ; Integrin alphaV ; metabolism ; Integrin beta1 ; metabolism ; Integrins ; genetics ; metabolism ; Lactic Acid ; chemistry ; Osteoblasts ; cytology ; Porosity ; Tissue Engineering ; methods