ISRIB facilitates the co-culture of human trophoblast stem cells and embryonic stem cells.

The embryo-like structures (embryoids) constructed by aggregating embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) have provided revolutionary tools for studying the intricate interaction between embryonic and extra-embryonic tissues during early embryonic development, which has been achieved in mice. However, due to the opposite dependence on some signalling pathways for in vitro culture of human ESCs (hESCs) and TSCs (hTSCs), particularly WNT and TGFß signalling pathways, which limits the construction of human post-implantation embryoids by aggregating hESCs and hTSCs. To overcome this challenge, here, by screening 1639 chemicals, we found that an inhibitor of integrated stress response, ISRIB, can replace WNT agonists and TGFß inhibitors to maintain the stemness and differentiation capacity of hTSCs. Thus, we developed an ISRIB-dependent in vitro culture medium for hTSCs, namely nTSM. Furthermore, we demonstrated that ISRIB could also maintain the hESC stemness. Using a 3D co-culture system (hESCs and hTSCs aggregate, ETA), we demonstrated that a 1:1 mixture of hESC culture medium (ESM) and nTSM improved the cell proliferation and organisation of both hESC- and hTSC-compartments and the lumenogenesis of hESC-compartment in ETAs. Overall, our study provided an ISRIB-dependent system for co-culturing hESCs and hTSCs, which facilitated the construction of human embryoids by aggregating hESCs and hTSCs.

Mutational Signatures Analysis of Micropapillary Components and Exploration of ZNF469 Gene in Early-stage Lung Adenocarcinoma with Ground-glass Opacities / 中国肺癌杂志

BACKGROUND@#In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration.@*METHODS@#A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases.@*RESULTS@#MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05).@*CONCLUSIONS@#The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.

Analysis of Risk Factors Associated with Early Childhood Caries.

Objective: To identify the main factors associated with early childhood caries by analyzing the risk factors of early childhood caries, thus providing a reference for developing prevention programs to reduce the risk of early childhood caries. Methods: We selected a total of 221 children aged 3-4 years from two kindergartens in Tongzhou District, Beijing for this study. We conducted oral examination and the caries activity test (Cariostat) on children and their parents / primary caregivers, and the parents / primary caregivers additionally answered a questionnaire survey. Based on the results, we comprehensively evaluated the caries status of children and statistically analyzed the caries-related factors to identify the relevant risk factors. Results: The mean age of children in the study children was 40.08 ± 2.65 months, with a caries prevalence rate of 54.97% and a mean caries value of 4.61. Early childhood caries was correlated with the intake frequency of sugary foods, intake of sugary foods before bedtime, frequency of tooth brushing, oral health knowledge of parents, caries susceptibility, and age of starting to brush teeth. Logistic regression analysis results showed that the intake frequency of sugary foods, oral health knowledge of parents, and caries susceptibility were the factors influencing early childhood caries, especially the intake frequency of sugary foods. Conclusion: The intake frequency of sugary foods, intake of sugary foods before bedtime, frequency of brushing teeth, oral health knowledge of parents, caries susceptibility, and age of starting to brush teeth were associated with early childhood caries. Among these, the intake frequency of sugary foods, oral health knowledge of parents, and caries susceptibility, especially the intake frequency of sugary foods, were the influencing factors.

Treatment of patent ductus arteriosus in very preterm infants in China / 中华儿科杂志

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

Clinical characteristics of children infected with SARS-CoV-2 Omicron variant combined with allergic disease / 中华儿科杂志

Objective: To investigate the clinical characteristics of children with allergic diseases suffering from SARS-CoV-2 Omicron variant strains. Methods: This was a cross-sectional study. A total of 43 pediatric patients with allergic diseases infected by SARS-CoV-2 from April 25, 2022 to June 8, 2022 in Shanghai Jiao Tong University School of Medicine were selected as the allergic disease group, while 114 cases without underlying diseases and 16 cases with other underlying diseases were selected as control groups diagnosed at the same period. Clinical data including clinical features, laboratory tests, duration of hospitalization, and the time to negative turn of novel coronavirus nucleic acid were collected and analysed. Kruskal-Wallis H test, chi-square test or Fisher exact test were used for comparison among three groups. Results: Among the 43 patients with allergic diseases, 28 were males and 15 were females, with an age of 4.4 (2.1, 8.2) years on admission, including 32 mild cases and 11 common cases. The allergic disease group included 20 cases (46.5%) of atopic dermatitis and eczema, followed by 14 cases (32.6%) of rhinitis, 8 cases (18.6%) of food allergies, 7 cases (16.3%) of asthma, 4 cases (9.3%) of allergic conjunctivitis and 2 cases (4.7%) of drug allergy. Among the 114 cases without underlying diseases, 57 were males and 57 were females, with an age of 2.8 (1.2, 5.6) years on admission, including 93 mild cases and 21 common cases. Among the 16 cases with other underlying diseases, 9 were males and 7 were females, with an age of 3.0 (2.6, 10.8) years on admission, including 13 cases mild and 3 cases common cases. Children with allergic diseases had higher frequency of sore throat and vomiting than those without underlying diseases (10 cases (23.3%) vs.9 cases (7.9%), 14 cases (32.6%) vs. 11 cases (9.6%), χ²=6.93, 12.24, both P<0.05). The lymphocyte count of patients with allergic disease was lower than those without underlying disease (1.1 (0.7,1.7)×109 vs. 1.6 (1.1,2.7)×109/L, H=-28.00,P=0.005). There were no significant differences in age, gender, typing of SARS-CoV-2, the duration of hospitalization, cycle threshold values of SARS-CoV-2 and the time to negative turn of novel coronavirus nucleic acid among the three groups (all P>0.05). Conclusions: Children with allergic diseases may suffer from sore throat and vomiting more frequently when infected with SARS-CoV-2 Omicron variant. The combination of allergic diseases hardly influenced the disease course of SARS-CoV-2 in children.

Meta analysis of the prevalence and influencing factors of WMSDs among dentists in China / 中华劳动卫生职业病杂志

Objective: To explore the relevant factors of work-related musculoskeletal disorders (WMSDs) among dentists through Meta analysis, providing a basis for the prevention and control of WMSDs among dentists. Methods: In April 2022, cross-sectional research literatures on the prevalence correlation of WMSDs among Chinese dentists were searched in databases such as China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, and Em Base database. The search was conducted from the establishment of the database until April 2022, literatures were selected using keywords such as musculoskeletal disorders and dentists. To extract gender, age, length of service, disease classification and other related influencing factors as indicator, and prevalence was selected as the outcome indicator. After evaluating the quality of the literatures, RevMan 5.3 software was used to calculate the combined RD (95%CI) values of the included literatures. Results: A total of 15 articles were included, with a total sample size of 3646 people. Meta analysis results showed that the prevalence of WMSDs among dentists in China was 80%, and the top three parts of the incidence rates were 65% of the waist, 58% of the neck, and 50% of the back. Gender, age, length of service, region and disease classification all increased the risk of WMSDs, and the combined effect size were 75%, 78%, 71%, 77% and 82% respectively (P<0.05) . Conclusion: The occurrence of WMSDs among dentists in China is related to multiple factors such as gender, age, length of service and disease classification. The above risk factors should be taken into account in the workplace and preventive measures should be actively implemented to prolong the working life of dentists.

The diversity of trophoblast cells and niches of placenta accreta spectrum disorders revealed by single-cell RNA sequencing.

Placenta accreta spectrum disorders (PAS) are severe pregnancy complications that occur when extravillous trophoblast cells (EVTs) invade beyond the uterine inner myometrium and are characterized by hypervascularity on prenatal ultrasound and catastrophic postpartum hemorrhage. The potential mechanisms remain incompletely understood. With single-cell RNA-sequencing analysis on the representative invasive parts and the normal part obtained from the same PAS placenta, we profiled the pathological landscape of invasive PAS placenta and deciphered an intensified differentiation pathway from progenitor cytotrophoblasts (CTBs) to EVTs via LAMB4 + and KRT6A + CTBs. In the absence of the decidua, the invasive trophoblasts of various differentiation states interacted with ADIRF + and DES + maternal stromal cells. The PAS-associated hypervascularity might be due to the enhanced crosstalk of trophoblasts, stromal cells and vascular endothelial cells. Finally, we presented an immune microenvironmental landscape of invasive PAS. The pathogenesis of PAS could be further explored with current resources for future targeted translational studies.

LMNA Determines Nuclear Morphology During Syncytialization of Human Trophoblast Stem Cells.

Upon implantation, the trophectoderm differentiates into the multi-nucleated primitive syncytiotrophoblast (pSTB) through a process called primary syncytialization to facilitate maternal-fetal interactions and to establish a pregnancy. However, ethical issues and limited access to human embryos around the time of embryo implantation hinder the investigation of the detailed molecular mechanisms underpinning this event in humans. Here we established human trophoblast stem cells (hTSCs) from human blastocysts. We characterized nuclear enlargement in STB differentiated from hTSCs, which recapitulate morphological nuclear features of pSTB in human embryos. Specifically, we revealed that CRISPR/Cas9-mediated LMNA disruption perturbated nuclear volume during hTSCs syncytialization. Overall, our results not only provide an interesting insight into mechanisms underlying nuclear enlargement during primary syncytialization but highlight the hTSCs as an indispensable model in understanding human trophoblast differentiation during implantation.

An engineered abcb4 expression model reveals the central role of NF-κB in the regulation of drug resistance in zebrafish.

Multi-drug resistance (MDR) is a phenomenon that tumor cells are exposed to a chemotherapeutic drug for a long time and then develop resistance to a variety of other anticancer drugs with different structures and different mechanisms. The in vitro studies of tumor cell lines cannot systematically reflect the role of MDR gene in vivo, and the cost of in vivo studies of transgenic mice as animal models is high. Given the myriad merits of zebrafish relative to other animal models, we aimed to establish a screening system using zebrafish stably expressing ATP-binding cassette (ATP-cassette) superfamily transporters and unveil the potential regulatory mechanism. We first used the Tol2-mediated approach to construct a Tg (abcb4:EGFP) transgenic zebrafish line with ATP-binding cassette (ABC) subfamily B member 4 (abcb4) gene promoter to drive EGFP expression. The expression levels of abcb4 and EGFP were significantly increased when Tg(abcb4:EGFP) transgenic zebrafish embryos were exposed to doxorubicin (DOX) or vincristine (VCR), and the increases were accompanied by a marked decreased accumulation of rhodamine B (RhB) in embryos, indicating a remarkable increase in DOX or VCR efflux. Mechanistically, Akt and Erk signalings were activated upon the treatment with DOX or VCR. With the application of Akt and Erk inhibitors, drug resistance was reversed with differing responsive effects. Notably, downstream NF-κB played a central role in the regulation of abcb4-mediated drug resistance. Taken together, the data indicate that the engineered Tg(abcb4:EGFP) transgenic zebrafish model is a new platform for screening drug resistance in vivo, which may facilitate and accelerate the process of drug development.

The Effects of Non-Surgical Periodontitis Therapy on the Clinical Features and Serological Parameters of Patients Suffering from Rheumatoid Arthritis as Well as Chronic Periodontitis.

OBJECTIVE: The present study aims to evaluate the effects of basic periodontal disease therapy on the general condition and serum inflammatory indicators of patients with rheumatoid arthritis (RA) combined with chronic periodontitis (CP). METHODS: Forty patients with RA were enrolled in the study and, based on the results of an oral examination and in line with the 2018 periodontitis diagnostic criteria, they were divided into a group with CP (the RA + CP group) and a group without CP (the RA group). Twenty-nine patients with CP who attended the periodontal department of our hospital were recruited as a group with only CP (the CP group), and 20 volunteers without any systemic or periodontal disease were recruited as a healthy control group (the H group). The periodontal and joint conditions of the subjects in the four groups were recorded; anti-cyclic citrullinated protein antibodies, interleukin 6 (IL-6), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and rheumatoid factor levels, which reflect the severity of the RA, were detected, and the differences between the groups were analyzed. The probing depth (PD), clinical attachment loss, and sulcus bleeding index (SBI), which reflect the severity of the periodontitis, were correlated with the factor levels. The RA + CP and CP groups received therapeutic intervention, and the differences in each indicator before and six weeks after the treatment were compared, and their data were compared with those of patients in the RA group and H groups. RESULTS: Compared with the RA group, the serum expressions of ESR, CRP, and IL-6 were significantly higher in the RA + CP group. There were significant differences in the levels of PD, SBI, IL-6, and CRP in the patients receiving basic periodontal disease therapy before and after the treatment. CONCLUSION: A relatively large proportion of patients with RA have chronic periodontitis, and the local inflammatory state of CP might exacerbate the systemic inflammatory response in RA. Basic periodontal disease therapy may improve the oral condition of patients with RA and reduce the serum levels of the inflammatory factors.

Application of massive open online course (MOOC) combined with flipped classroom in pediatrics education / 中华医学教育探索杂志

Blended teaching method has become an important part of the educational reform. Massive open online courses (MOOC) combined with flipped classroom in pediatrics education consists of online courses, flipped classroom and online communication. Students are promoted to engage in education actively through the online homework, tests, discussions and examinations, thus reaching the best teaching effect. This paper aims to introduce the establishment and accomplishments of this blended teaching method in Pediatrics education in Fudan University.

Analysis of clinical characteristics of influenza virus pneumonia and risk factors for severe pneumonia in 711 Children / 国际儿科学杂志

Objective:To investigate the clinical characteristics of influenza A and influenza B pneumonia and the risk factors of severe influenza pneumonia in children.Methods:The epidemiology, clinical characteristics, laboratory tests and pathogens of co-infection in children with pneumonia caused by influenza A virus and influenza B virus, and the risk factors of severe influenza pneumonia were retrospectively analyzed.Results:(1) The cases of influenza A infection accounted for 65.1% and those with influenza B infection accounted for 32.9% among the 711 children with influenza pneumonia.The dominant strain was Influenza B Victoria virus in spring and summer, influenza A(H 3N 2) virus in autumn, and influenza A(H1N1) virus in winter.The dominant strain was influenza A virus at the age of < 1 year and ~3 years, influenza A virus and influenza B virus at the age of ~6 years, and influenza B virus at the age of ≥6 years.(2) The gastrointestinal symptoms were more common in children with influenza B pneumonia compared with those with influenza A pneumonia(53.4% vs 44.7%, χ2=4.728, P=0.030), but crackles and wheezing were more common in children with influenza A pneumonia compared with those with influenza B pneumonia(80.1% vs 70.5%, 36.9% vs 25.6%, χ2=8.945, 8.093, all P<0.05). (3) The percentage of decreased lymphocyte count in children with influenza B pneumonia was higher than those with influenza A pneumonia(5.6% vs 1.9%, χ2=6.633, P=0.010). (4) Mixed Mycoplasma Pneumoniae was more common in children with influenza B pneumonia compared with those with influenza A pneumonia(23.9% vs 10.8%, χ2=20.789, P<0.001), and mixed virus and bacteria were more common in children with influenza A pneumonia compared with those with influenza B pneumonia(15.8% vs 8.1%, 50.1% vs 41.9%, χ2=7.934, 4.221, all P<0.05). (5) Multivariate logistic regression analysis showed that age <2 years( OR=1.886, 95% CI 1.149~3.096, P=0.012), increased LDH( OR=1.736, 95% CI 1.080~2.790, P=0.023), the percentage of lymphocyte decreased( OR=2.762, 95% CI 1.669~4.571, P<0.001) and the percentage of CD3 + decreased ( OR=6.019, 95% CI 3.993~9.331, P<0.001)were risk factors for severe influenza pneumonia. Conclusion:Among hospitalized children with influenza pneumonia, there were some differences in the age of infection, clinical characteristics, laboratory tests and pathogens of co-infection between the cases caused by influenza B and influenza A, and clinicians should remain vigilant for the occurrence of severe influenza pneumonia.

Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma.

BACKGROUND: Cyclooxygenase 2 (COX-2) is an inducible enzyme which promotes tumorigenesis in many types of cancers. Genetic knockout of COX-2 significantly suppresses the tumorigenesis of skin squamous cell carcinoma (SCC). However, COX-2 inhibitor treatment only showed mild to moderate inhibition on SCC in previous reports. The aim of this study is to solve this contradiction and to re-evaluate the therapeutic potential of targeting COX-2 in SCC. METHODS: COX-2 was knocked down by shRNA in two different SCC cell lines, A431 and SCC-13. The cells proliferation and migration capacity were evaluated by cell growth curves and monolayer scratch assay, respectively. Cancer cells with COX-2 knockdown were also xenografted into Balb/c nude mice and tumor growth curves were recorded over time. In addition, we changed the drug administration route and intraperitoneally injected COX-2 inhibitor celecoxib into mice to evaluate its anti-cancer activity. RESULTS: Knockdown of COX-2 exhibited mild or even no effect on cell proliferation and migration in two different SCC cell lines in vitro. However, when cancer cells were xenografted into nude mice, knockdown of COX-2 significantly suppressed proliferation of cancer cells in tumors. At last, intraperitoneal injection instead of oral administration of COX-2 inhibitor celecoxib potently suppressed tumor growth. CONCLUSIONS: Our results indicate that COX-2 might impact on the interaction between cancer cells and surrounding microenvironments rather than on cancer cells directly, and demonstrate that targeting COX-2 is a very promising therapeutic approach for SCC treatment.

Interleukin-18 and post-stroke depression / 国际脑血管病杂志

Post-stroke depression (PSD) can seriously affect the outcome and quality of life of patients with stroke. However, due to the lower diagnostic rate, a large number of patients with PSD have not been treated in time and have a poor outcome. Therefore, only early detection, early diagnosis and early treatment of PSD can improve the prognosis and quality of life of patients with stroke. In recent years, a large number of studies on serum biomarkers have tried to find objective indicators related to PSD. Among them, interleukin-18 is associated with the pathogenesis of stroke and PSD, which may be attributed to its polymorphism and constitutive expression in the brain, especially the role of serum level changes in the risk stratification and outcome of acute ischemic stroke. This article reviews the role of interleukin-18 in the pathogenesis of PSD.

Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice

BackgroundCoronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-inflammations in COVID-19 is not well known. Methods and FindingsIn this study, we developed a Spike protein-pseudotyped (Spp) lentivirus with the proper tropism of SARS-CoV-2 Spike protein on the surface and tracked down the fate of Spp in wild type C57BL/6J mice receiving intravenous injection of the virus. A lentivirus with vesicular stomatitis virus glycoprotein (VSV-G) was used as the control. Two hours post-infection (hpi), Spp showed more than 27-75 times more viral burden in the lungs than other organs; it also exhibited about 3-5 times more viral burden than VSV-G lentivirus in the lungs, liver, kidney and spleen. Acute pneumonia was evident in animals 24 hpi. Spp lentivirus was mainly found in LDLR+ macrophages and pneumocytes in the lungs, but not in MARC1+ macrophages. IL6, IL10, CD80 and PPAR-{gamma} were quickly upregulated in response to infection of Spp lentivirus in the lungs in vivo as well as in macrophage-like RAW264.7 cells in vitro. We further confirmed that forced expression of the Spike protein in RAW264.7 cells could significantly increase the mRNA levels of the same panel of inflammatory factors. ConclusionsOur results demonstrate that the Spike protein of SARS-CoV-2 alone can induce cellular pathology, e.g. activating macrophages and contributing to induction of acute inflammatory responses.

Clinical characteristics of 106 patients with neurological diseases and co-morbid coronavirus disease 2019: a retrospective study

ObjectivesTo describe the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with co-morbid neurological symptoms. DesignRetrospective case series. SettingHuoshenshan Hospital in Wuhan, China. ParticipantsFrom 4 February to 14 April 2020, 106 patients with neurological diseases were enrolled from all patients in the hospital with confirmed COVID-19 and divided into a severe group and a non-severe group according to their COVID-19 diagnosis. Main outcome measuresClinical characteristics, laboratory results, imaging findings, and treatment methods were all retrieved through an electronic medical records system and recorded in spreadsheets. ResultsThe mean (standard deviation, SD) age of patients was 72.7 (11.8) years, and 64 patients were male (60.4%). Among patients with co-morbid neurological diseases, 81 had a previous cerebral infarction (76.4%), 20 had dementia (18.9%), 10 had acute cerebral infarction (9.4%), 5 had sequelae of cerebral haemorrhage (4.7%), 4 had intracranial mass lesions (3.8%), 3 had epilepsy (2.8%), 2 had Parkinsons disease (1.9%), and 1 had myelopathy (0.9%). Fever (n = 62, 58.5%) was the most common symptom. The most common neurological symptoms were myalgia (n = 26, 24.5%), followed by extremity paralysis (n = 20, 18.9%), impaired consciousness (n = 17, 16%), and positive focal neurological signs (n = 42, 39.6%). Eight patients (7.5%) died. There were more patients with altered mental status in the severe group than in the non-severe group (6 [10.2%] vs. 0, P = 0.033). The inflammatory response in the severe group was more significant than that in the non-severe group. There were more patients taking anticoagulant drugs (25 [42.4%] vs. 4 [8.5%], P < 0.001) and sedative drugs (22 [37.3%] vs. 9 [19.1%], P = 0.041) in the severe group than in the non-severe group. Amid all 93 patients with cerebrovascular diseases, only 32 (34.4%) were taking aspirin, 13 (14%) taking clopidogrel, and 33 (35.5%) taking statins. ConclusionsPatients with COVID-19 with co-morbid neurological diseases had an advanced age, a high rate of severe illness, and a high mortality rate. Among the neurological symptoms, altered mental status was more common in patients with severe COVID-19 with co-morbid neurological diseases.

Endothelial inflammatory markers and cerebral microbleeds / 国际脑血管病杂志

Cerebral microbleeds (CMBs) is a imaging manifestation of cerebral small vessel disease. At present, more and more opinions believe that vascular endothelial injury plays an important role in the pathogenesis of CMBs. The destruction of the blood-brain barrier and inflammatory response caused by vascular endothelial dysfunction may promote the occurrence and development of CMBs. At the same time, the deposition of hemosiderin around the lesion of CMBs may also trigger an inflammatory response. However, the relevant mechanisms and causality have not yet been fully elucidated. This article reviews the vascular endothelial inflammatory factors related to CMBs and their mechanism in the pathogenesis of CMBs.

Progress in Role of FEZF1-AS1 in Non-small Cell Lung Cancer / 中国肺癌杂志

Nowadays, accumulating evidence indicates that long non-coding RNA (lncRNA) play vital roles in tumorigenesis. As a newly discovered lncRNA, FEZ family zinc finger 1-antisense RNA 1 (FEZF1-AS1) is markedly upregulated in various malignant tumors including non-small cell lung cancer (NSCLC). Aberrant expression of FEZF1-AS1 is related to clinical characteristics of patients with NSCLC and suggests poor prognosis. Moreover, FEZF1-AS1 can regulate numerous biological processes, such as cell proliferation, migration and invasion through different mechanisms. In this article, we systematically summarize the recent research progress of FEZF1-AS1 in NSCLC, which might be a novel target for clinical therapy.

Management of critically ill neonates with extracorporeal membrane oxygenation: analysis of nine cases / 中华围产医学杂志

Objective To assess the performance of extracorporeal membrane oxygenation (ECMO) in the treatment of neonates with critical diseases.Methods This study retrospectively analyzed the clinical data of nine critically ill neonates treated with ECMO because of cardiopulmonary failure due to respiratory disorders in Children's Hospital of Fudan University from August 2015 to April 2018.General information,diagnosis,indications and approaches of ECMO,clinical procedure of ECMO,laboratory results,weaning time,survival rate before discharge,length of stay,and mechanical and neurological complications were collected and described.Results (1) There were six male and three female patients with an average gestational age and body weight of 39.6 weeks (35-41 weeks) and 3 600 g (2 580-4 650 g),respectively.Out of them,six cases survived after successfully weaning from ECMO.(2) Sepsis (two cases),meconium aspiration (two cases),pulmonary hypertension (three cases),diaphragmatic hernia (one case) and pulmonary dysplasia (one case) were diagnosed in the patients.All underwent veno-arterial (VA) ECMO using centrifugal pump.The median age to initiate ECMO was 40 h (23-100 h) after birth,and the median duration of ECMO support was 240 h (70-370 h).During the treatment with ECMO,cholestasis,intracranial hemorrhage and vocal cord paralysis occurred in three cases,and mechanical complications (mainly were bleeding,hemolysis,oxygenated membrane leakage and embolization) occurred in five cases.The mean length of hospital stay for the six survivors was 24 d (20-49 d),and two of them developed neurological complications mainly manifested as cerebral infarction.There were three died cases.One was a baby with diaphragmatic hernia who received hernia repair during ECMO after which celiac space syndrome and necrotizing enterocolitis were developed and his parents refused further treatment.In the second case,the parents gave up treatment when no improvement was achieved after two weeks of ECMO support.While the last case was complicated by severe cerebral hemorrhage during ECMO and died after receiving no further treatment.Conclusions ECMO is newly applied in the treatment of neonates in China and of great significance for critically ill neonates.However,much need to be learned about its utilization in this population considering the mortality and disability rate are still high.

Application of simulation-based medicine education in pediatric resident training / 中国实用儿科杂志

Simulation-based medicine education(SBME)refers to the clinical teaching method of using medical simulation equipment or simulator design to simulate clinical scenes,replacing the actual content of real medical scenes in an interactive way and the actual patient. Simulation is particularly important in pediatric resident training,and a large amount of evidencebased evidence confirms that simulation training used in resident training ensures patients' safety and improves patients' outcomes. The paper mainly expounds the application principle,theoretical basis,main content and the method of establishing the simulation center in the training of pediatric resident in simulated medical education,intending to promote the further development of simulation training in the training of domestic pediatric resident.