Technical guideline for school sanitary and anti epidemic measures after flood disasters / 中国学校卫生

Abstract@#Flood disasters are the common public health emergencies, mainly leading to environmental damage, water pollution, food pollution, vector breeding, infectious disease epidemic and other risk factors of sanitary and anti epidemic work. The guideline has been formulated with reference to the technical documents such as Guideline for Environmental Sanitation Disposal and Preventive Disinfection in Flooded Areas and Technical Proposal for Sanitary and Anti epidemic Measures after Flood Disasters, as well as the latest research progress at home and abroad. In order to guide the sanitary and anti epidemic measures in flooded areas, protect the health and safety of students and teachers and ensure the normal educational and teaching order, the guideline introduces the key measures that should be taken by schools, teachers and students in flood striken areas.

The characteristics and associated factors of functional limitation in patients with rheumatoid arthritis / 中华内科杂志

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction

The human coronavirus HCoV-19 infection can cause acute respiratory distress syndrome (ARDS), hypercoagulability, hypertension, extrapulmonary multiorgan dysfunction. Effective antiviral and anti-coagulation agents with safe clinical profiles are urgently needed to improve the overall prognosis. We screened an FDA approved drug library and found that an anticoagulant agent dipyridamole (DIP) suppressed HCoV-19 replication at an EC50 of 100 nM in vitro. It also elicited potent type I interferon responses and ameliorated lung pathology in a viral pneumonia model. In analysis of twelve HCoV-19 infected patients with prophylactic anti-coagulation therapy, we found that DIP supplementation was associated with significantly increased platelet and lymphocyte counts and decreased D-dimer levels in comparison to control patients. Two weeks after initiation of DIP treatment, 3 of the 6 severe cases (60%) and all 4 of the mild cases (100%) were discharged from the hospital. One critically ill patient with extremely high levels of D-dimer and lymphopenia at the time of receiving DIP passed away. All other patients were in clinical remission. In summary, HCoV-19 infected patients could potentially benefit from DIP adjunctive therapy by reducing viral replication, suppressing hypercoagulability and enhancing immune recovery. Larger scale clinical trials of DIP are needed to validate these therapeutic effects.

ACE2 expression by colonic epithelial cells is associated with viral infection, immunity and energy metabolism

Respiratory disease caused by the 2019 novel coronavirus (2019-nCoV) pneumonia first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for 2019-nCoV. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. Upon analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (IBD), we found that ACE2 expression in the colonocytes was positively associated with genes regulating viral infection, innate and cellular immunity, but was negatively associated with viral transcription, protein translation, humoral immunity, phagocytosis and complement activation. In summary, we suggest that ACE2 may play dual roles in mediating the susceptibility and immunity of 2019-nCoV infection.

Potential therapeutic effects of dipyridamole in the severely ill patients with COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.

Application of 16 row spiral CT chest low dose scanning in the diagnosis of pulmonary tuberculosis / 中国基层医药

Objective@#To evaluate the clinical value of 16-slice spiral CT low dose chest scanning in the diagnosis of pulmonary tuberculosis.@*Methods@#From June 13, 2014 to June 20, 2017, 80 patients with pulmonary tuberculosis in Yuyao People's Hospital were selected in the study.The conventional chest dose(control group) and low dose(observation group) of 16-slice spiral CT were used.The diagnostic accuracy, radiation dose of the two methods, lymph node or vascular space display and image features were observed.@*Results@#The diagnostic accuracy of the two methods had no statistically significant difference (P>0.05). The dose product length, the CT dose index in the observation group were (32.98±2.57) mGycm, (44.29±3.47), respectively, which were significantly lower than those in the control group[(127.66±5.03)mGycm, (44.29±3.47)](t=106.01, 21.05, all P<0.05). The display clarity of lymph nodes or vascular space of the observation group was 90.00%, which of the control group was 92.50%, there was no statistically significant difference between the two groups (P>0.05). The rates of ground glass shadow, burr of the observation group were 29.32%, 31.58%, respectively, which were significantly lower than those of the control group(41.35%, 47.37%), the differences were statistically significant (χ2=4.21, 6.94, all P<0.05). Other signs detection probability are similar between the two groups and had no statistically significant differences (all P>0.05).@*Conclusion@#The low dose chest CT scan with 16 rows spiral CT has high clinical value, low radiation dose and high diagnostic accuracy in the diagnosis of pulmonary tuberculosis.

Application of 16 row spiral CT chest low dose scanning in the diagnosis of pulmonary tuberculosis / 中国基层医药

Objective To evaluate the clinical value of 16-slice spiral CT low dose chest scanning in the diagnosis of pulmonary tuberculosis.Methods From June 13,2014 to June 20,2017,80 patients with pulmonary tuberculosis in Yuyao People＇s Hospital were selected in the study.The conventional chest dose( control group) and low dose(observation group) of 16 -slice spiral CT were used.The diagnostic accuracy,radiation dose of the two methods,lymph node or vascular space display and image features were observed.Results The diagnostic accuracy of the two methods had no statistically significant difference (P>0.05).The dose product length,the CT dose index in the observation group were (32.98 ± 2.57) mGycm,(44.29 ± 3.47),respectively,which were significantly lower than those in the control group[(127.66 ± 5.03)mGycm,(44.29 ± 3.47)] ( t=106.01,21.05,all P<0.05).The display clarity of lymph nodes or vascular space of the observation group was 90.00% ,which of the control group was 92.50% ,there was no statistically significant difference between the two groups (P>0.05).The rates of ground glass shadow,burr of the observation group were 29.32% ,31.58% ,respectively,which were significantly lower than those of the control group (41.35% ,47.37% ),the differences were statistically significant ( χ2 =4.21,6.94,all P <0.05).Other signs detection probability are similar between the two groups and had no statistically significant differences (all P>0.05).Conclusion The low dose chest CT scan with 16 rows spiral CT has high clinical value, low radiation dose and high diagnostic accuracy in the diagnosis of pulmonary tuberculosis.

4.4 Å Resolution Cryo-EM structure of human mTOR Complex 1

Mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates signals from growth factors, cellular energy levels, stress and amino acids to control cell growth and proliferation through regulating translation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 Å resolution. The mTORC1 comprises a dimer of heterotrimer (mTOR-Raptor-mLST8) mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase-like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for substrate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance for substrate entry to the catalytic cavity of mTORC1. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regulatory mechanism of mTORC1 pathway.

Structural insight into mechanisms for dynamic regulation of PKM2

Pyruvate kinase isoform M2 (PKM2) converts phosphoenolpyruvate (PEP) to pyruvate and plays an important role in cancer metabolism. Here, we show that post-translational modifications and a patient-derived mutation regulate pyruvate kinase activity of PKM2 through modulating the conformation of the PKM2 tetramer. We determined crystal structures of human PKM2 mutants and proposed a "seesaw" model to illustrate conformational changes between an inactive T-state and an active R-state tetramers of PKM2. Biochemical and structural analyses demonstrate that PKM2(Y105E) (phosphorylation mimic of Y105) decreases pyruvate kinase activity by inhibiting FBP (fructose 1,6-bisphosphate)-induced R-state formation, and PKM2(K305Q) (acetylation mimic of K305) abolishes the activity by hindering tetramer formation. K422R, a patient-derived mutation of PKM2, favors a stable, inactive T-state tetramer because of strong intermolecular interactions. Our study reveals the mechanism for dynamic regulation of PKM2 by post-translational modifications and a patient-derived mutation and provides a structural basis for further investigation of other modifications and mutations of PKM2 yet to be discovered.

The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B

KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHD1KDM5B interacts with unmethylated H3K4me0. Our NMR structure of PHD1KDM5B in complex with H3K4me0 revealed that the binding mode is slightly different from that of other reported PHD fingers. The disruption of this interaction by double mutations on the residues in the interface (L325A/D328A) decreases the H3K4me2/3 demethylation activity of KDM5B in cells by approximately 50% and increases the transcriptional repression of tumor suppressor genes by approximately twofold. These findings imply that PHD1KDM5B may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B.

Development of nanometer hydroxyapatite complex materials——Cytotoxicity test of nano-hydroxyapatite by MTT-assay / 实用口腔医学杂志

Objective: To evaluate the cytotoxicity of nano-hydroxyapatite. Methods: Mouse lung fibroblast L-929 and primary cultured human periodontal ligament fibroblast-like cells (PDLF) were cultured in the medium of extraction of nano-hydroxyapatite or commerce hydroxyapatite at 100%,50%,10% and 0% (control) respectively.Cell growth was tested by MTT assay and the cell relative growth rate (RGR) was calculated.The cytotoxicity was graded by generally accepted standard.Results: RGR of both cell lines cultured in nano-hydroxyapatite extraction was higher than that in control HA. In 7-day culture the cytotoxicity grade of HA was 1 in 100% of HA extraction medium and 0 in 100% of nano-hydroxyapatite extraction,or in 50% and 10% of nano-hydroxyapatite or control HA extraction medium.Primarily cultured PDLF showed lower RGR than L-929 under the same condition. Conclusion: Nano-HA do not have cytotoxic effect.