Single-cell Multi-omics Integration for Unpaired Data by a Siamese Network with Graph-based Contrastive Loss

Single-cell omics technology is being rapidly developed to measure the epigenome, genome, and transcriptome across a range of cell types. However, integrating omics data from different modalities is still challenging. Here, we propose a variation of the Siamese neural network framework called MinNet, which is trained to integrate multi-omics data on the single-cell resolution by utilizing graph-based contrastive loss. By training the model and testing it on several benchmark datasets, we showed its accuracy and generalizability in integrating scRNA-seq with scATAC-seq, and scRNA-seq with epitopes data. Further evaluation demonstrated our models unique capacity in removing the batch effect, which is a common problem in actual practice. To show how the integration impacts downstream analysis, we established model-based smoothing and cis-regulatory element inferring method and validated it with external pcHi-C evidence. Finally, the framework was applied to a COVID-19 dataset to compensate the original work with integration-based analysis, showing its necessity in single-cell multi-omics research.

Tao-Hong-Si-Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway.

Limb ischemia reperfusion (LIRI) injury is associated with serious local and systemic effects. Reperfusion may augment tissue injury in excess of that produced by ischemia alone. Calcium overloading and inflammation are considered to be two of the pathological mechanisms of limb ischemia/reperfusion (I/R) injury. Tao-Hong-Si-Wu decoction (THSWD) is a traditional Chinese herbal medicine with a powerful anti-inflammatory properties. We studied the probable restorative effect of THSWD on limb I/R-induced calcium overloading and inflammation in myoblast obtained from gastrocnemius muscle tissues of Sprague-Dawley rats (Frizzled Z5,a wnt5a blocker; KN-93, a calmodulin-dependent protein kinase II (CamkII) blocker; XeC, a IP3R blocker as positive controls). The simulated ischemia and reperfusion(I/R) solutions were used to imitate LIRI environment. The results showed that after I/R treatment, the secretion of proinflammatory factors (TNF-α and IL-1ß) and Wnt5a/Ca2+ signal molecules (wnt5a, camkII, and IP3R) upregulated significantly, the Ca2+ concentration enhanced too in myoblast cells. THSWD pretreatment decreased the secretion of TNF-α and IL-1ß, Ca2+ concentration; and abated the Wnt5a/Ca2+ signal molecules of wnt5a, camkII and IP3R expression activated by I/R injury; but could not abated the Wnt11 and protein kinase C (PKC) expression significantly, the results was similar with Frizzled Z5 treatment cells. Our research illustrated that THSWD may have a mitigating effect on LIRI targeting Wnt/IP3R/CAMKII but not Wnt/IP3R/PKC signaling pathway for the first time. This study may encourage the use of THSWD in the critical clinical settings with LIRI.

Z-scores for fetal atrial volume using real-time three-dimensional echocardiographic Xplane imaging in normal fetuses / 中华超声影像学杂志

Objective To establish Z-scores reference ranges for fetal atrial volume in normal fetuses for accurate assessment of fetal cardiac structure and function . Methods Two hundred ninty-three normal fetuses with gestational ages between 18 to 38 weeks were investigated .Biparietal diameter (BPD) , femur length (FL) and gestational age (GA) were measured .Left atrial volume (LAV) and right atrial volume ( RAV ) were obtained using echocardiographic Xplane imaging . Subsequently , the optimal regression equation was established with BPD ,FL and GA as the independent variable and LAV and RAV as the dependent variable ,and then Z-scores of LAV and RAV were calculated . Results The linear regression equation of LAV and FL was Y＝0 .056×FL －1 .791 ( r ＝0 .952) ;the linear regression equation of RAV and FL was Y＝0 .057×FL －1 .833 ( r ＝0 .942) ;the linear regression equation of LAV and BPD was Y＝0 .046×BPD－2 .289 ( r ＝0 .910) ;the linear regression equation of RAV and BPD was Y＝0 .047×BPD－2 .348 ( r ＝0 .903) ;the linear regression equation of LAV and GA was Y ＝ 0 .122 × GA －2 .403 ( r ＝0 .952) ;the linear regression equation of RAV and GA was Y ＝0 .125×GA －2 .456 ( r ＝0 .942) . There was significant heteroscedasticity of standard deviation ( SD ) with increasing independent variables ,then weighted regression of absolute residuals was used in order to minimize the effect of heteroscedasticity ,and the linear regression equation was established . The linear regression equation of LAV-SD and FL was Y＝0 .005×FL －0 .119 ( r ＝0 .272) ;the linear regression equation of RAV-SD and FL was Y＝0 .005×FL －0 .104 ( r ＝0 .240) ;the linear regression equation of LAV-SD and BPD was Y＝ 0 .00375×BPD －0 .125 ( r＝0 .210) ;the linear regression equation of RAV-SD and BPD was Y＝0 .00375×BPD －0 .10875 ( r ＝0 .192) ;the linear regression equation of LAV-SD and GA is Y＝0 .0125×GA －0 .21125 ( r ＝0 .346) ;the linear regression equation of RAV-SD and GA was Y＝0 .0125×GA －0 .20875 ( r ＝0 .308) . According to these equations ,the Z-score calculation formula for LAV was ( measured LAV-predicted LAV from BPD , FL and GA)/SD of predicted LAV ; Z-score calculation formula for RAV was ( measured RAV －predicted RAV from BPD ,FL and GA)/SD of predicted RAV . Conclusions Fetal Z-scores references for the LAV and RAV can be established using common fetal biometrical parameters ( including FL ,BPD and GA utilizing statistical methods based on a large sample size) . This enhances accurate assessment of growth and development of fetal cardiac structures ,and provides novel insights for the determination of fetal atrial volume in fetuses with congenital heart disease .

Evaluation of ventricular systolic function in fetuses with congenital heart disease by spatio-temporal image correlation with M-mode display / 中华超声影像学杂志

Objective To evaluate the effectiveness of spatio-temporal image correlation with M-mode display ( STIC-M ) in monitoring fetal left ventricular systolic function in fetuses with congenital heart disease(CHD) . Methods Five hundred and thirty-six normal fetuses and 34 fetuses with CHD( 29 without hydrops and 5 with hydrops) were involved in the study . Left ventricular fractional shortening ( LVFS) was measured using STIC-M . The data of normal fetuses was used to construct reference ranges of LVFS for assessment of fetuses with CHD . Results The LVFS of the normal fetuses [ range :26 .8％ - 42 .9％ , mean :( 34 .9 ± 4 .1) ％ ] was negatively correlated with gestational age ( r = - 0 .16 , P < 0 .001) . Compared with the normal controls ,LVFS was significantly decreased in CHD fetuses with hydrops ( P < 0 .001) . However ,there was no significant difference in LVFS between normal controls and CHD fetuses without hydrops ( P > 0 .05) . Conclusions STIC-M is a new method that can be used to measure LVFS to evaluate fetal ventricular systolic function . The fetal ventricular contractile function of CHD fetuses without hydrops may not be damaged or is in compensation stage . The fetuses with cardiac hydrops generally become lower .

A study of influence of Xuebijing injection on expression of triggering receptor-1 expression on myeloid cell in patients with severe sepsis / 中国中西医结合急救杂志

Objective To investigate the effects of Xuebijing injection on expression of myeloid cell triggering receptor-1(TREM-1)and the plasma levels of soluble TREM-1(sTREM-1),tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)in patients with severe sepsis. Methods Twenty patients with severe sepsis admitted into Critical Care Medicine Department,Affiliated Hospital of Nantong University were given comprehensive treatments according to the guidelines for management of severe sepsis and septic shock(2004),and they were divided into Xuebijing group and control group(each 20 cases). The Xuebijing injection group was given Xuebijing injection 50 mL,3 times daily for 5-7 days followed by regular treatments. The changes in blood TREM-1 mRNA expression and plasma concentrations of sTREM-1,TNF-α,and IL-6 were detected before and after treatments on the 3rd and 5th day,and the above indexes were compared between the two groups. Results Before treatments,there were no significant differences in TREM-1 mRNA expression and levels of sTREM-1,TNF-α,IL-6 between two groups (all P>0.05). The TREM-1 expression and plasma concentrations of sTREM-1,TNF-α,and IL-6 of two groups were declined after treatments compared to their baselines,the degree of decline being more prominent in Xuebijing group〔TREM-1 mRNA 3 days:1.065±0.277 vs. 1.217±0.301,t=-3.267,P=0.047;5 days:0.912±0.239 vs. 1.071±0.254,t=-5.072,P=0.032;sTREM-1(ng/L):146.93±13.76 vs. 176.22±19.46,t=-5.442,P=0.033;TNF-α(ng/L):77.51±11.28 vs. 107.72±13.17,t=-4.355,P=0.032;IL-6(ng/L):288.35±14.59 vs. 323.89± 24.51, t=-3.941,P=0.028〕. Conclusion Early implication of Xuebijing injection is of great significance in patients with severe sepsis,it may reduce the expression level of TREM-1 and serum levels of downstream inflammatory mediators,that is beneficial to the control of inflammatory responses and improvement of systemic inflammatory response syndrome in such patients.

Value of serum procalcitonin in the predicting prognosis of bacterial infection in critically ill patients / 中华急诊医学杂志

Objective To explore the value of procalcitonin (PCT) in the prediction of the prognosis and severity of bacterial infection in critically ill patients.Methods A total of 116 eligible patients with bacterial infection admitted in the intensive care unit were enrolled in this prospective study from February,2012 through November,2012.Within 24 hours after admission,the serum PCT was determined with immune-chromatography and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score of patients was calculated.Based on the 28-day clinical outcome of patients,the patients were divided into fatal group (n =36) and survival group (n =80).The differences in PCT and APACHE Ⅱ score between the two groups were compared with t test or rank-sum test.The correlation between PCT and APACHE Ⅱ score was determined with Spearman's correlation analysis.Both PCT and APACHE Ⅱ score were analyzed separately and jointly with area under receiver operator characteristic curve (ROC curve,AUC) to predict 28-day survival.Comparison of prediction performance for predicting 28-day survival of patients with bacterial infection between PCT and APACHE Ⅱ was made with U test.Results PCT concentration was significantly higher in fatal group than that in survival group [5.36 (2.07,25) vs.0.24 (1.00,2.14)] (Z =5.596,P ＜0.01).APACHE Ⅱ score within 24 hour after admission was significantly higher in fatal group than that in survival group (24.30 ± 6.71) vs.(16.03 ± 7.23),t =6.147,P ＜ 0.01.Positive correlation between PCT and APACHE Ⅱscore was found to be statistical significance (r =0.388,P＜ 0.01).When rates of 28-day survival in patients were predicted by using PCT and APACHE Ⅱ score,the areas of under curve were 0.804 and 0.792,respectively.AUC of PCT was tenuously larger than that of APACHE Ⅱ score (U =0.2073,P =0.802).Using PCT and APACHE Ⅱ score together to predict 28-day survival,AUC (0.817) was increased.The joint prediction performance was higher than that of either alone,increasing the sensitivity to 90.7％ and the specificity to 75.2％.Conclusions Serum PCT can reflect the severity of the illness and prognosis of infectious disease in the intensive care unit.It can serve as a sensitive marker of predicting 28-day survival.Combining PCT and APACHE Ⅱ score together can increase the prognostic value.

Application of enteral and parenteral nutrition support in critically ill patients / 肠外与肠内营养

Objective: To investigate the effect of enteral and parenteral nutrition on critically ill patients in ICU. Methods: Nutrition support were analyzed in 56 critically ill patients in ICU,with 32 cases supported by enteral nutrition and 24 cases supported by parenteral nutrition.Results: 52 patients restored to health and 4 patients died from original disease.It was found that serum prealbumin was improved(P

Clinincal analysis of appendix schistosomiasis complicated with acute appendicitis / 中国血吸虫病防治杂志

The clinical data of 275 appendix shistosomasis cases complicated with acute appendicitis were retrospectively analyzed,and the result showed that the incidence rate of appendix schistosomasis complicated with acute appendicitis whose complications were serious was high,which deserved to be concerned.