Decoding of persistent multiscale structures in complex biological networks

In any omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewise, protein communities revealed from protein networks can vary widely in sizes depending on the method. Here we use the concept of "persistent homology", drawn from mathematical topology, to identify robust structures in data at all scales simultaneously. Application to mouse single-cell transcriptomes significantly expands the catalog of identified cell types, while analysis of SARS-COV-2 protein interactions suggests hijacking of WNT. The method, HiDeF, is available via Python and Cytoscape.

An insertion unique to SARS-CoV-2 exhibits superantigenic character strengthened by recent mutations

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. These symptoms and the associated laboratory values strongly resemble toxic shock syndrome, an escalation of the cytotoxic adaptive immune response triggered upon the binding of pathogenic superantigens to MHCII molecules and T cell receptors (TCRs). Here, we used structure-based computational models to demonstrate that the SARS-CoV-2 spike (S) exhibits a high-affinity motif for binding TCR, interacting closely with both the - and {beta}-chains variable domains complementarity-determining regions. The binding epitope on S harbors a sequence motif unique to SARS-CoV-2 (not present in any other SARS coronavirus), which is highly similar in both sequence and structure to bacterial superantigens. Further examination revealed that this interaction between the virus and human T cells is strengthened in the context of a recently reported rare mutation (D839Y/N/E) from a European strain of SARS-CoV-2. Furthermore, the interfacial region includes selected residues from a motif shared between the SARS viruses from the 2003 and 2019 pandemics, which has intracellular adhesion molecule (ICAM)-like character. These data suggest that the SARS-CoV-2 S may act as a superantigen to drive the development of MIS-C as well as cytokine storm in adult COVID-19 patients, with important implications for the development of therapeutic approaches. SignificanceAlthough children have been largely spared from severe COVID-19 disease, a rare hyperinflammatory syndrome has been described in Europe and the East Coast of the United States, termed Multisystem Inflammatory Syndrome in Children (MISC). The symptoms and diagnostic lab values of MIS-C resemble those of toxic shock, typically caused by pathogenic superantigens stimulating excessive activation of the adaptive immune system. We show that SARS-CoV-2 spike has a sequence and structure motif highly similar to those of bacterial superantigens, and may directly bind to the T cell receptors. This sequence motif, not present in other coronaviruses, may explain the unique potential for SARS-CoV-2 to cause both MIS-C and the cytokine storm observed in adult COVID-19 patients.

The different impact between late-phase of limb ischemia preconditioning and early-phase on patients with percutaneous coronary intervention / 中国介入心脏病学杂志

Objective To investigate the difference of late-phase of limb ischemia preconditioning (L-LIP) verse early-phase (E-LIP) on patients with percutaneous coronary intervention (PCI).Methods A total of 160 patients with unstable angina pectoris who were planned to undergo PCI were divided equally into two groups at random.The late-phase of limb ischemia preconditioning group (80 patients) were provided with L-LIP (three 5-minute inflations up to 200mmHg by applying the sphygmomanometer cuff around the right upper arm,followed by 5-min intervals of reperfusion,twice a day) 3 days before PCI.The Earlyphase of limb ischemia preconditioning group (80 patients) were provided with E-LIP (method as above)2 hours before PCI.Comparison of procedural parameters during PCI and the levels of cTnT,CK-MB,hs-CRP were made 24 hours after PCI.Estimation of the rate of adverse events at 1 year between the two groups was evaluated by Kaplan-Meier analysis.Results Compared to the E-LIP group,the rates of angina,arrhythmia and TIMI flow ≤ 2 during PCI were significantly lower in the L-LIP group (all P ＜ 0.05).At 24 hours after PCI,the levels of cTnT and CK-MB were declined more significantly in the L-LIP group[(11.52±2.41) pg/ml vs.(27.53±4.78)pg/ml,P =0.021;(14.11±2.87)Iu/L vs.(30.23±5.17)Iu/L,P =0.032].There was no difference in the level of hs-CRP between the 2 groups [(128±0.71)mg/dl vs.(1.33±0.69)mg/dl,P =0.742].The Kaplan-Meier survival curve showed that the incidence rate of adverse events in the L-LIP group at l year was lower than the E-LIP group (3.75％ vs.13.75％,P =0.024).Conclusions L-LIP is more effective to in protecting myocardial cell in patients with unstable angina pectoris undergoing elective PCI and may reduce the rate of future adverse event.

Effects of calponin-1 gene silencing on the biological behavior of uterine smooth muscle cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of calponin-1 expression inhibition on the proliferation , invasiveness, apoptosis and cytoskeleton of uterine smooth muscle cells, and explore the molecular mechanism of calponin-1 in the uterine smooth muscle cells for labor onset.</p><p><b>METHODS</b>siRNA-calponin-1 adenovirus plasmid was constructed and transfected into primarily cultured uterine smooth muscle cells. The proliferation, invasiveness and apoptosis of the cells were determined by MTT assay, matrigel invasion assays and flow cytometry, respectively. Rhodamine-Phalloidin was used for labeling filamentous actin (F-actin), and the morphology and the distribution of F-actin was observed under fluorescence microscopy and analyzed quantitatively.</p><p><b>RESULTS</b>The motor ability of uterine smooth muscle cells decreased significantly after transfection with siRNA-calponin-1 adenovirus plasmid (P<0.05). The transfected cells showed thinner, loosened and irregular F-actin microfibers, and the cells in the empty vector and blank control groups showed thicker and longer F-actin microfibers.</p><p><b>CONCLUSION</b>Inhibition of calponin-1 expression can inhibit uterine smooth muscle cell migration and cause the morphological change and rearrangement of F-actin without affecting its proliferation and apoptosis in vitro, suggesting that the morphological change and rearrangement of F-actin of uterine smooth muscle cell may be one of the important mechanisms in the labor onset.</p>

The application and significance in prenatal diagnosis using G-banding, fluorescence in situ hybridization and comparative genomic hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the procedure and the value of G-banding, fluorescence in sit hybridization (FISH) and comparative genomic hybridization (CGH) techniques in prenatal diagnosis.</p><p><b>METHODS</b>Karyotype analyses with three diagnostic procedures, G-banding, G-banding and FISH, G-banding, FISH and CGH, were performed in the amniotic fluid samples taken from 102 fetuses at gestational ages 16-24 weeks. And the significance was valued in prenatal diagnosis.</p><p><b>RESULTS</b>In the first procedure of karyotype analysis, 98 cases were diagnosed, 2 cases were not conformed while 2 cases were failed in all 102 cases. In the second procedure, 2 cases were determined, 1 case was not conformed and 1 case was still failed. In the third step, 2 cases were diagnosed. The diagnostic rate of the karyotype reached to 100% (102/102 cases) using all the three procedures. In total, seven cases with chromosomal abnormality were diagnosed. Four cases, 1 case and 2 cases were identified in the first step (4/7, 57.1%), the second (1/7, 14.3%) and the third (2/7, 28.5%), respectively.</p><p><b>CONCLUSION</b>It can help improve the diagnostic rate of chromosomal aberrations and standardize diagnostic procedure to perform the three detecting steps in prenatal diagnosis.</p>

Systematic continuous sequence approach in diagnosing fetal deformity / 中南大学学报(医学版)

OBJECTIVE@#To explore the value of ultrasonographic evaluation in fetal deformity in prenatal diagnosis by a systematic continuous sequence approach (SCSA).@*METHODS@#Successive prenatal ultrasonographic evaluation was performed to monitor the whole anatomic structure,form, posture and movement of 16,685 fetuses during gestation aging 14 approximately 40(+3) weeks.@*RESULTS@#Satisfactory ultrasonic images were obtained in 16,627 fetuses using the SCSA (99.65%). Of them, 514 abnormal fetuses were confirmed after subsequent labor or induced labor and 498 abnormal fetuses were correctly diagnosed using SCSA during prenatal stage (96.89%). Whereas 16 fetuses missed recognition (3.11%). Its sensitivity, specificity, positive and negative predictive value of diagnosis on fetal deformity were 96.98%, 99.96%, 98.66%, and 99.90 %, respectively.@*CONCLUSION@#SCSA in prenatal ultrasonographic evaluation of the fetal structure and malformation is reliable and accurate.

A clinical observation on therapeutic effect of colon purification on hepatic encephalopathy / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To observe therapeutic effect of colon purification on hepatic encephalopathy.</p><p><b>METHODS</b>117 patients with hepatic encephalopathy treated in our hospital were randomly divided into the treatment group (59 cases) and the control group (58 cases). Routine anti-coma hepaticum treatments were carried out in both treatment and control groups, and colon purification treatment was performed in the treatment group on basis of routine anti-coma hepaticum. The changes in symptoms and signs were observed, the grading scores of hepatic encephalopathy were evaluated, liver function was tested and blood ammonia level was determined before and after treatment in the two groups. Time for regaining consciousness was recorded after treatment in the two groups.</p><p><b>RESULTS</b>The symptoms and signs were obviously improved, time for regaining consciousness was shortened, the grading scores decreased, and serum aminotransferase activity and bilirubin level and blood ammonia level significantly decreased in the treatment group as compared with those of the control group. Total effective rate in the treatment was significantly higher than that in the control group and death rate in the treatment group was significantly lower than that in the control group.</p><p><b>CONCLUSION</b>Colon purification treatment is effective for hepatic encephalopathy due to cirrhosis.</p>

Scanning of drug targets related to uterus contraction from the uterine smooth muscles by cDNA microarray / 中南大学学报(医学版)

OBJECTIVE@#To screen the differentially expressed gene profile from the smooth muscles in the fundus uterus at the active stage of labor, and to provide candidate genes for picking out the drug targets related to uterine contraction.@*METHODS@#Differentially expressed genes of uterine smooth muscles in the corpus from pro and post spontaneous parturition and those induced by oxytocin,as well as those from the corpus and the lower portion spontaneous parturition,were scanned respectively by human full-length genetic cDNA microarray with 8064 probe sets. Semi-quantitative RT-PCR was applied to testify the expression of voltage dependent calcium channel-L subtype (CACNA). The differentially expressed genes in the structure and function of the drug targets were picked out by bio-informatics to serve as candidate drug targets related to uterine contraction.@*RESULTS@#The expressions of 29 genes were upregulated in fundus smooth muscles from the pro and post natural parturition, the pro and post inductive parturition of oxytocin, and the natural parturition. The expression of CACNA gene in RT-PCR was in accordance with that in the microarray. Among the 29 genes, neuromedin B receptor (NMBR) gene and neuropeptide Y (NPY) gene were the genes which not only had the targets of uterine contracted medicine, but also could contract the uterine. The differential expression ratios of NMBR in the above 3 types of uterine myometrium were 6.9,11.3, and 9.0, respectively while those of NPY were 6.0,29.8, and 2.9 respectively.@*CONCLUSION@#NMBR, whose expression in the uterine smooth muscles is always up-regulated at different parturition conditions, is likely to be an ideal candidate target of uterotonic drugs.

Clinical analysis of pregnancy complicated with systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVE@#To investigate the interacting effects between pregnancy and flares of systemic lupus erythematosus (SLE) and to explore the best occasion for SLE patients' conception and the management during the pregnancy.@*METHODS@#Thirty one cases of pregnancy complicated with SLE were investigated retrospectively, among whom 18 were in remission of SLE at the beginning of conception (Group A), and the other 13 either had high-activity of the disease or were first diagnosed as SLE during the pregnancy (Group B). Various doses of prednisone were administered to control SLE.@*RESULTS@#SLE flares still occurred in 6 cases in Group A, but in all cases in Group B. Compared with Group A, the rates of fetal loss and early delivery were significantly higher in Group B (P < 0.05), while the survival rate and the weight of the new born were notably decreased in Group B (P < 0.05).@*CONCLUSION@#Pregnancy and SLE interacted with each other unfavorably. Selection of remission stage for conception and proper management during the pregnancy could significantly improve the maternal-fetal safety.

Fetal posterior cranial fossa in the second and third trimester / 中南大学学报(医学版)

OBJECTIVE@#To examine the normal range of the width of posterior cranial fossa (WPCF) in the second and third trimester by ultrasonography, and to investigate its relationship with fetal congenital and chromosome abnormality.@*METHODS@#WPCF of 2484 fetus (gestational age from 14 to 41 weeks) was measured by ultrasonograph routinely, and the infants were followed up.@*RESULTS@#In 2848 fetus, 2772 were normal and 76 were abnormal. WPCF increased before 32 weeks, decreased after 33 weeks, the largest value of WPCF was 13.4 mm. The occurrence rate of WPCF> or =8 mm in normal fetus was 8.84%, and that in abnormal fetus was 17.46%. Most fetuses with chromosome abnormality had normal WPCF in the second trimester, but some fetuses with remarkable broadening in the late stage. Some abnormal fetuses (such as water head, Dandy-Walker's syndrome etc) showed significant extension of WPCF.@*CONCLUSION@#WPCF increases before 32 weeks, decreases after 33 weeks;and can be easily measured during 29 - 32 weeks. WPCF of some fetus with chromosome abnormality or with congenital abnormality is remarkably broadened in the late stage. The fetus of WPCF> or =10 mm should be followed up closely, and antenatal diagnosis should be done if WPCF is more than 14 mm.