Disentangling the common genetic architecture and causality of rheumatoid arthritis and systemic lupus erythematosus with COVID-19 outcomes: genome-wide cross trait analysis and bi-directional Mendelian randomization study

COVID-19 may cause a dysregulation of the immune system and has complex relationships with multiple autoimmune diseases, including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, little is known about their common genetic architecture. We analysed summary-level genetic data from the latest COVID-19 host genetics consortium and consortia on RA and SLE to examine the shared genetic etiology and causal relationship between COVID-19 and RA/SLE. The cross-trait meta-analysis identified 46, 47, and 19 shared genetic loci for severe COVID-19, COVID-19 hospitalization, and SARS-CoV-2 infection with RA, and 19, 24, and 11 shared loci with SLE, respectively. Shared genes were significantly enriched in the spleen, lung, whole blood, and small intestine, and involved in immune function, inflammation and coagulation process. Co-localization analysis identified eight shared loci in TYK2, IKZF3, COL11A2, PSORS1C1, MANEAL and COG6 genes for COVID-19 with RA, and four in CRHR1, FUT2 and NXPE3 genes for COVID-19 with SLE. Bi-directional Mendelian randomization analysis suggested RA is associated with a higher risk of COVID-19 hospitalization, and COVID-19 is not related to RA or SLE. Our novel findings improved the understanding of the common genetic aetiology shared by COVID-19, RA and SLE, and suggested an increased risk of COVID-19 hospitalization in people with higher genetic liability to RA.

Characterization of key aroma compounds and relationship between aroma compounds and sensory attributes in different aroma types of Fu brick tea.

Aroma is one of the most important sensory properties of tea. Floral-fungal aroma type, ripe-fungal aroma type and fresh-fungal aroma type were the main aroma types of Fu brick tea by QDA. A total of 112 volatile compounds were identified and quantified in tea samples by HS-SPME/GC-MS analysis. Ten voaltiles in floral-fungal aroma type, eleven voaltiles in ripe-fungal aroma type, and eighteen voaltiles in fresh-fungal aroma type were identified as key aroma compounds for the aroma characteristics formation in three aroma types of Fu brick tea. In addition, PLS analysis revealed that 3,4-dehydro-ß-ionone, dihydro-ß-ionone, (+)-carotol and linalool oxide Ⅱ were the key contributors to the 'floral and fruity' attribute, α-terpineol contributed to 'woody' and 'stale' attributes, and thirteen aroma compounds related to 'green' attribute. Taken together, these findings will provide new insights into the formation mechanism of different aroma characteristics in Fu brick tea.

Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture, which has not been clarified yet. To fill this gap, we leveraged summary-level genetic data from the latest COVID-19 host genetics consortium and UK Biobank and examined the shared genetic etiology and causal relationship between COVID-19 and VTE. The cross-trait analysis identified 8, 11, and 7 shared loci between VTE and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, in 13 genes involved in coagulation and immune function and enriched in the lung. Co-localization analysis identified eight shared loci in ABO, ADAMTS13 and FUT2 genes. Bi-direction Mendelian randomization suggested that VTE was associated with higher risks of all COVID-19 related traits, and SARS-CoV-2 infection was associated with higher risk of VTE. Our study provided timely evidence and novel insights into the genetic etiology between COVID-19 and VTE.

pIVW: A novel Mendelian Randomization Method Accounting for Weak Instruments and Horizontal Pleiotropy with Applications to the COVID-19 Outcomes

SO_SCPLOWUMMARYC_SCPLOWMendelian randomization (MR) utilizes genetic variants as instrumental variables (IVs) to estimate the causal effect of an exposure variable on an outcome of interest even in the presence of unmeasured confounders. However, the popular inverse-variance weighted (IVW) estimator could be biased in the presence of weak IVs, a common challenge in MR studies. In this article, we develop a novel penalized inverse-variance weighted (pIVW) estimator, which adjusts the original IVW estimator to account for the weak IV issue by using a penalization approach to prevent the denominator of the pIVW estimator from being close to zero. Moreover, we adjust the variance estimation of the pIVW estimator to account for the presence of balanced horizontal pleiotropy. We show that the recently proposed debiased IVW (dIVW) estimator is a special case of our proposed pIVW estimator. We further prove that the pIVW estimator has smaller bias and variance than the dIVW estimator under some regularity conditions. We also conduct extensive simulation studies to demonstrate the performance of the proposed pIVW estimator. Furthermore, we apply the pIVW estimator to estimate the causal effects of five obesity-related exposures on three coronavirus disease 2019 (COVID-19) outcomes. Notably, we find that hypertensive disease is associated with an increased risk of hospitalized COVID-19; and peripheral vascular disease and higher body mass index are associated with increased risks of COVID-19 infection, hospitalized COVID-19 and critically ill COVID-19.

A Two-Sample Robust Bayesian Mendelian Randomization Method Accounting for Linkage Disequilibrium and Idiosyncratic Pleiotropy With Applications to the COVID-19 Outcome

Mendelian randomization (MR) is a statistical method exploiting genetic variants as instrumental variables to estimate the causal effect of modifiable risk factors on an outcome of interest. Despite wide uses of various popular two-sample MR methods based on genome-wide association study summary level data, however, those methods could suffer from potential power loss or/and biased inference when the chosen genetic variants are in linkage disequilibrium (LD), and also have relatively large direct effects on the outcome whose distribution might be heavy-tailed which is commonly referred to as the idiosyncratic pleiotropy phenomenon. To resolve those two issues, we propose a novel Robust Bayesian Mendelian Randomization (RBMR) model that uses the more robust multivariate generalized t-distribution (Arellano-Valle and Bolfarine, 1995) to model such direct effects in a probabilistic model framework which can also incorporate the LD structure explicitly. The generalized t-distribution can be represented as a Gaussian scaled mixture so that our model parameters can be estimated by the EM-type algorithms. We compute the standard errors by calibrating the evidence lower bound using the likelihood ratio test. Through extensive simulation studies, we show that our RBMR has robust performance compared to other competing methods. We also apply our RBMR method to two benchmark data sets and find that RBMR has smaller bias and standard errors. Using our proposed RBMR method, we find that coronary artery disease is associated with increased risk of critically ill coronavirus disease 2019 (COVID-19). We also develop a user-friendly R package RBMR (https://github.com/AnqiWang2021/RBMR) for public use.

The influence of bundled ligation of the pancreatic stump on postoperative pancreatic fistula of distal pancreatectomy / 中华消化外科杂志

Objective:To investigate the influence of bundled ligation of the pancreatic stump on postoperative pancreatic fistula (POPF) of distal pancreatectomy (DP).Methods:The retrospective case-control study was conducted. The clinical data of 60 patients with diseases in pancreatic body and tail who underwent DP in the Affiliated Hospital of Inner Mongolia Medical University from January 2011 to August 2018 were collected. There were 24 males and 36 females, aged from 19 to 68 years, with a median age of 45 years. Of the 60 patients, 36 cases undergoing dissection of pancreas with Endo-GIA stapler were allocated into non-bundled group, and 24 cases undergoing bundled ligation of the pancreatic stump with No.10 or No.7 suture at the site over 1 cm of the resection site before dissection of pancreas were allocated into bundled group. Observation indicators: (1) postoperative situations; (2) analysis of risk factors for POPF of DP. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test or ANOVA test. Measurement data with skewed distribution were represented as M (range).Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test and multivariate analysis was conducted using the Logistic regression model. Results:(1) Postoperative situations: the amylase concentration, cases with biochemical fistula, cases with grade B pancreatic fistula, cases with complications, time to extubation, duration of postoperative hospital stay, total hospital expenses were (2 629±592)U/L, 14, 5, 7, (11.9±0.7)days, (13.6±0.7)days, (49 430±1 626)yuan in non-bundled group and (683±312)U/L, 3, 1, 2, (9.7±0.6)days, (11.3±0.5)days, (44 767±1 163)yuan in bundled group, respectively. There were significant differences in the amylase concentration, cases with biochemical fistula, time to extubation, duration of hospital stay, total hospital expenses between the two groups ( t=2.528, χ2=1.512, t=2.341, 2.311, 2.111, P<0.05), and there was no significant difference in the cases with grade B pancreatic fistula or cases with complications between the two groups ( χ2=1.512, 1.394, P>0.05). (2) Analysis of risk factors for POPF of DP. Results of univariate analysis showed that tumor diameter and bundled ligation of the pancreatic stump were related factors of patients undergoing pancreatic fistula after DP ( χ2=4.462, 5.061, P<0.05). Results of multivariate analysis showed that bundled ligation of the pancreatic stump was an independent influencing factor of patients undergoing pancreatic fistula after DP ( odds ratio=0.187, 95% confidence interval as 0.037-0.954, P<0.05). Conclusions:Bundled ligation of the pancreatic stump was an independent influencing factor of patients undergoing pancreatic fistula after DP. Bundled ligation of the pancreatic stump can effectively reduce the incidence of POPF, especially biochemical fistula, the time to extubation, duration of postoperative hospital stay and total hospital expenses, and promote patient recovery after DP.

Effects of thoracoscopy combined with laparoscopy on lung function and tumor micrometastasis in patients with thoracic esophageal cancer / 中华内分泌外科杂志

Objective:To investigate the effect of thoracoscopy combined with laparoscopy on lung function and tumor micrometastasis in patients with thoracic esophageal cancer.Methods:109 patients with thoracic esophageal cancer admitted from Mar. 2018 to Jul. 2019 in our hospital were divided into study group (60 cases) and the control group (49 cases) . The study group underwent thoracoscopy and laparoscopy assisted surgery, while the control group underwent traditional surgical resection of esophageal cancer. The differences of lung function, RBC immune function and the expression of invasive gene in the lesions between the two groups were compared.Results:Three days after the operation, maximum ventilation per minute (MVV) , forced expiratory volume for 1 s (FEV1) and vital capacity (VC) of the two groups were all decreased ( P<0.01) , but they were significantly higher in the study group than in the control group[ (69.90±7.07) vs (48.62±5.09) , (75.12±7.93) vs (42.99±4.81) , (74.57±7.30) vs (41.37±4.69) ( P<0.01) ]. mRNA of matrix metalloproteinase 9 (MMP9) and tumor necrosis factor receptor-related protein 1 (TRAP1) in the two groups were all decreased ( P<0.01) , while they were significantly higher in the study group than in the control group [ (0.54±0.09) vs (0.42±0.06) , (0.52±0.08) vs (0.41±0.06) ( P<0.01) ]. mRNA of Krüppel-like factor 4 (KLF4) and E-cad-herin in the two groups were all increased ( P<0.01) , while it was significantly lower in the study group than in the control group[ (2.87±0.30) vs (3.17±0.36) , (2.92±0.32) vs (3.19±0.38) ( P<0.01) ]. RBC immune complex rosette rate (RBC-ICR) in the study group was higher than that on the first day before operation ( P<0.01) , and gradually decreased from the first day after operation, and recovered to the preoperative level on the third day after operation. At the end of operation, red blood cell C3b receptor rosette rate (RBC-C3bRR) and red blood cell adhesion tumor cell rosette rate (TRR) in the study group were all decreased compared with those on the first day before operation ( P<0.01) , and gradually increased on the first day after operation in the study group, and recovered to the preoperative level on the third day after operation. Except for the first day before surgery, there were statistically significant differences in red blood cell immune function indexes at other time points between the study group and the control group[At the end of the operation: (30.29±4.80) vs (34.68±5.47) , (16.02±1.58) vs (12.03±1.17) , (17.50±2.86) vs (12.59±2.26) ; 1 d after operation: (29.13±4.19) vs (35.01±5.29) , (20.98±2.86) vs (16.23±2.40) , (22.50±2.56) vs (17.39±2.34) ; 3 d after operation: (26.01±3.80) vs (31.50±5.01) , (23.30±3.37) vs (18.02±2.79) , (25.80±2.10) vs (21.19±2.60) ( P<0.01) ]. Conclusion:In patients who need radical surgery for thoracic esophageal cancer, the application of thoracoscopy combined with laparoscopy has little effect on lung function, red blood cell immunity, and tumor micrometastasis, which is worth promoting.

Derivation of endothelial cells from porcine induced pluripotent stem cells by optimized single layer culture system

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

Derivation of endothelial cells from porcine induced pluripotent stem cells by optimized single layer culture system

Regenerative therapy holds great promise in the development of cures of some untreatable diseases such as cardiovascular diseases, and pluripotent stem cells (PSCs) including induced PSCs (iPSCs) are the most important regenerative seed cells. Recently, differentiation of human PSCs into functional tissues and cells in vitro has been widely reported. However, although porcine reports are rare they are quite essential, as the pig is an important animal model for the in vitro generation of human organs. In this study, we reprogramed porcine embryonic fibroblasts into porcine iPSCs (piPSCs), and differentiated them into cluster of differentiation 31 (CD31)-positive endothelial cells (ECs) (piPSC-derived ECs, piPS-ECs) using an optimized single-layer culture method. During differentiation, we observed that a combination of GSK3β inhibitor (CHIR99021) and bone morphogenetic protein 4 (BMP4) promoted mesodermal differentiation, resulting in higher proportions of CD31-positive cells than those from separate CHIR99021 or BMP4 treatment. Importantly, the piPS-ECs showed comparable morphological and functional properties to immortalized porcine aortic ECs, which are capable of taking up low-density lipoprotein and forming network structures on Matrigel. Our study, which is the first trial on a species other than human and mouse, has provided an optimized single-layer culture method for obtaining ECs from porcine PSCs. Our approach can be beneficial when evaluating autologous EC transplantation in pig models.

Derivation of endothelial cells from porcine induced pluripotent stem cells by optimized single layer culture system

Fuzhuan Brick Tea Attenuates High-Fat Diet-Induced Obesity and Associated Metabolic Disorders by Shaping Gut Microbiota.

An increasing amount of evidence suggests that the metabolic improvement of high-fat diet (HFD)-induced obese mice by Fuzhuan brick tea (FBT) is associated with gut microbiota. However, the causalities between FBT and gut microbiota have not yet been elucidated and the underlying mechanisms of action remain unclear. To impart direct evidence for the essential role of gut microbiota in the attenuation of obesity by FBT, the effects of FBT on healthy mice and microbiota-depleted mice that were treated with antibiotics were compared in an HFD-induced obesity mouse model. The results showed that FBT dramatically ameliorated obesity, serum lipid parameters, blood glucose homeostasis, hepatic steatosis, adipocyte hypertrophy, and tissue inflammation. However, the microbiota-depleted mice with single bacterium (Escherichia-Shigella) after antibiotic treatment were resistant to FBT-induced antiobesity and metabolic improvement. The beneficial effects of FBT resulted from its shift on gut microbiota composition and structure in mice. HFD-induced increase in the phyla Firmicutes/Bacteroidetes (F/B) ratio was remarkably restored by FBT. Furthermore, FBT-induced increase in abundances of beneficial bacteria Clostridiaceae, Bacteroidales, and Lachnospiraceae and decreases in harmful Ruminococcaceae, Peptococcaceae, Peptostreptococcaceae, and Erysipelotrichaceae were causal antecedents for FBT to reduce obesity and improve metabolic disorders.

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

BACKGROUND: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients. METHODS: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables. RESULTS: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years. CONCLUSIONS: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.

The length of guide RNA and target DNA heteroduplex effects on CRISPR/Cas9 mediated genome editing efficiency in porcine cells

The clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is a versatile genome editing tool with high efficiency. A guide sequence of 20 nucleotides (nt) is commonly used in application of CRISPR/Cas9; however, the relationship between the length of the guide sequence and the efficiency of CRISPR/Cas9 in porcine cells is still not clear. To illustrate this issue, guide RNAs of different lengths targeting the EGFP gene were designed. Specifically, guide RNAs of 17 nt or longer were sufficient to direct the Cas9 protein to cleave target DNA sequences, while 15 nt or shorter guide RNAs had loss-of-function. Full-length guide RNAs complemented with mismatches also showed loss-of-function. When the shortened guide RNA and target DNA heteroduplex (gRNA:DNA heteroduplex) was blocked by mismatch, the CRISPR/Cas9 would be interfered with. These results suggested the length of the gRNA:DNA heteroduplex was a key factor for maintaining high efficiency of the CRISPR/Cas9 system rather than weak bonding between shortened guide RNA and Cas9 in porcine cells.

Prediction of microvascular invasion in hepatocellular carcinoma patients by preoperative neutrophil-lymphocyte ratio and cancer-related factors / 中华肝胆外科杂志

Objective To predict the presence of MVI,the general clinicopathological of HCC patients' data of the preoperative neutrophil-lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR),altplatelet ratio (APRI) were evaluated.Methods 143 cases of HCC patients who underwent radical resection and ≤ 5 cm of tumor diameter in Chifeng Clinical Medical School of Inner Mongolia Medical University from January 2011 to December 2014 were analysed retrospectively and followed up.The relationship between NLR,PLR,APRI and other clinical parameters was evaluated.Results According to ROC Curve,the NLR truncation value was 2.00,PLR to 115.00,APRI 1.6.The single factor analysis of x2 test showed that NLR (x2=6.419;P＜0.05),APRI (x2=3.975;P＜0.05),AFP (x2=33.37;P＜0.05),Degree of differentiation (x2 =9.839;P＜0.05) were significant differences between MVI positive (MVI+) and negative (MVI-) groups,and the difference was statistically significant;Logistic regression multifactor analysis showed that NLR (OR 2.678;95％ CI 1.033～6.944;P＜0.05) and AFP (OR 1.724;95％CI 1.023～2.905;P＜0.05) are independent predictors of MVI.Conclusion Preoperative NLR and AFP are convenient,economical and reliable hematological indices for predicting the presence of MVI in HCC patients.

Effect of phosphorus deficiency on erythrocytic morphology and function in cows

The aim of this study was to evaluate the influence of phosphorus (P) deficiency on the morphological and functional characteristics of erythrocytes in cows. Forty Holstein-Friesian dairy cows in mid-lactation were randomly divided into two groups of 20 each and were fed either a low-P diet (0.03% P/kg dry matter [DM]) or a control diet (0.36% P/kg DM). Red blood cell (RBC) indices results showed RBC and mean corpuscular hemoglobin decreased while mean corpuscular volume increased significantly (p < 0.05) in P-deficient cows. Erythrocyte morphology showed erythrocyte destruction in P-deficient cows. Erythrocytes' functional characteristics results showed total bilirubin and indirect bilirubin concentrations and aspartate transaminase and alanine transaminase activity levels in the serum of P-deficient cows were significantly higher than those in control diet-fed cows. Activities of superoxide dismutase and glutathione peroxidase in erythrocytes were lower, while the malondialdehyde content was greater, in P-deficient cows than in control diet-fed cows. Na⁺/K⁺-ATPase and Mg²⁺-ATPase activities were lower in P-deficient cows than in control diet-fed cows; however, Ca²⁺-ATPase activity was not significantly different. The phospholipid composition of the erythrocyte membrane changed and membrane fluidity rigidified in P-deficient cows. The results indicate that P deficiency might impair erythrocyte integrity and functional characteristics in cows.

The pulmonary arterial hypertension of patients on maintained hemodialysis is positively associated with the decreased percent of CD8 T cell in the peripheral blood independently / 中华肾脏病杂志

Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH.Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently:PAH group (pulmonary artery systolic pressure,PASP ＞ 35 mmHg) and non-PAH group (PASP≤35 mmHg).The related clinical,biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3,CD4,CD8 and CD69 with flow cytometry.Logistic regression analysis was used to find out the relationship between PAH and T cell subsets.Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender,age,mean systolic and diastolic pressure,dialysis durations,morbidities of hypertension and diabetes,smoking rate,and left ventricular diameter.Compared with the non-PAH group,the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells,but a much higher left atrial diameter (LAD),Interventricular septum thickness,left ventricular posterior wall thickness,and NT-proBNP.The percentage of T cells,CD4 T cells and CD4 CD69 T cells showed no difference between the two groups.Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells.Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients,and CD8 T cells may play an important role in the genesis of PAH.

Effectiveness of monitoring common chronic diseases in community by integrated traditional Chinese medicine and western medicine / 中华全科医师杂志

The monitoring of chronic diseases , including diabetes , hypertension , coronary heart disease and osteoporosis among residents in the community was conducted by Shanghai Changfeng Community Health Service Center , and the identification of physical constitution according to Traditional Chinese Medicine system was performed simultaneously .The medical checkup report and advices on prevention and treatment was provided to the residents , so that they know better about their health condition and its management .

In vitro development and chimeric efficiency of mouse-porcine interspecies chimeric embryos in different culture systems / 生物工程学报

With the advancements of stem cells and regenerative medicine, interspecies chimera has become a hot topic and will pave a new way of providing donor sources in organ transplantation. However, the interspecies chimera is confronted with a number of scientific questions and technical obstacles, including selections of appropriate embryonic stage and appropriate culture medium; those factors will deeply influence the developmental balance between donor cells and receptor embryos. Due to its relatively rapid reproductive cycle and similar organ size to human's, porcine is a very potential donor candidate to study these questions. To compare the development and chimeric efficiency of interspecies embryos, we tested and evaluated three different culture systems, PZM-3 (Porcine zygotic medium), culture medium for iPSCs (N2B27) and 3.5 h of N2B27 before PZM-3 (N2B27(3.5 h)), and two different embryonic stages, 8-cell and blastocyst in mouse-porcine chimeric embryos using parthenogenetically activated porcine embryos and mouse induced pluripotent stem cells (miPS). The results showed that, PZM-3 was beneficial for both development of chimeric embryos and miPSCs proliferation in porcine embryos in the 8-cell injection group. After early blastocyst injection, the chimeric efficiency did not appear significantly different among the three culture systems but was lower than 8-cell injection. In summary, the results suggest that 8-cell injection and PZM-3 culture medium are more beneficial to the in vitro development and chimeric efficiency of mouse-porcine chimeric embryos.

Association of intradialytic hypotension and 5-year mortality in maintaining hemodialysis patients / 中华肾脏病杂志

Objective To assess the risk factors of intradialytic-hypotension (IDH) and the prognosis of IDH among maintenance hemodialysis (MHD) patients for the prevention and treatment of IDH.Methods 276 MHD patients were enrolled during Jan.2009 to Mar.2009.Intradialytic blood pressure was monitored during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mmHg or in mean artery pressure (MAP) more than 10 mmHgassociated with clinical events and need for interventions.Dialysis-related information was collected.Kaplan-Meier method,log-rank test,logistic regression and Cox regression analyses were performed to examine the association between IDH and survival,using a follow-up through 31 May 2014.Results A total of 276 patients were recruited.The incidence rate of IDH was 40.9％.163 patients with no-IDH (＜ 1/10 hypotensive events/3 months) served as controls.113 patients with IDH (≥ 1/10 hypotensive events/3 months) were identified among all 276 patients.Multivariate logistic regression analysis showed that age,ultrafiltration rate,gender,serum NT-proBNP,serum albumin and aortic rool inside dimension (AoRD) were associated with IDH among MHD patients.During the 5-year follow-up,74 patients died,with a mortality rate 5.2 per 100 person-year.Kaplan-Meier survival curve showed significant difference of overall and CV mortality rates between 2 groups.The multivariate Cox regression model indicated that IDH increased the risk of death (HR=1.572,95％CI 1.077-2.293,P=0.019).So did the rise of LVMI (HR=1.010,95％CI 1.009-1.085,P=0.020).Conclusion Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia and shorter AoRD are independent risk factors for IDH among MHD patients.LVMI can predict the outcome of MHDpatients.Intradialytic hypotension is an independent risk factor for long-term mortality in MHD patients.

Use of the way to find and manage renal pedicle along the ureteral ascending method in retroperitoneosocpic radical nephrectomy / 中华泌尿外科杂志

Objective To explore the operating skills of finding and dissecting renal pedicle in retroperitoneosocpic radical nephrectomy.Methods From April 2011 to April 2015,224 patients with renal tumors were treated by retroperitoneosocpic radical nephrectomy.Along the ureteral ascending methodis used to find renal pedicle for 126 cases(the research group):First found ureter in the iliac crest,the ureter was nearest psoas major here and waseasy to find.Along the ureteral upward until to the renal pelvis and the superior border of renal pelvis is the renal pedicle.77 male and 49 female cases,Age 42 to 84 years,(56.6 ± 9.0) years old on average.Sixty-nine tumors were located in left kidney,and 59 in the right kidney.The mean diameter of renal tumor was(5.3 ± 1.1)cm.There were 25 cases of T1a N0 M0,75 T1b N0 M0,23 of T2 N0 M0,3 of T1bN1M0.Over the same period uplift in he kidney central method is used to find renal pedicle for 98 cases.64 male and 34 female cases,Age 27 to 81 years,(57.9 ± 8.3)years old on average.52 tumors were located in left kidney,and 46 in the right kidney.The mean diameter of renal tumor was (5.5 ± 1.4)cm.There were 19 cases of T1aN0M0,61 T1bN0M0,16 of T2N0M0,2 of T1bN1 M0.Results The differences were significant for Looking for renal pedicle time(2.2 ± 1.1 vs.4.5 ±2.0) min,operation time (73.7 ±67.3 vs.90.1 ±87.5)min,hemorrhage volume(69.8 ±42.7 vs.89.7 ±89.2) ml,the incidence of complications (3 vs.9) between the study group and the control group (P ＜ 0.05).The difference were not significant in postoperative hospital stay (7.5 ± 0.8 vs.7.3 ± 0.8) d,exhaust time (2.1 ± 0.6 vs.2.2 ± 0.6) d between two group.All the operations were performed successfully in the research group,with no conversion to open and transfusion.Major complications included 3 cases of vessel injury.Hemostasis was performed with metal clips and suture.In the control group,ena cava rupture in 3 cases,left lumbar veins rupture in 3 cases,retroperitoneal hematoma in 2 case,mild pulmonary embolism in 1 case.two case performed open operation owing to vena cava rupture.The vena cava rupture transit open surgery in 2 cases,and Hemostasis was performed with metal clips in 1 case of vena cava rupture and on the left side of the lumbar veins rupture was managed by suture,titanium clips and bipolar electrocautery;Retroperitoneal hematoma improved by conservative treatment;Pulmonary embolism improved by medical consultation after thrombolysis.Conclusions Retroperitoneosocpic radical nephrectomy with the method of along the ureteral ascending was safe and could quickly locate and ligate the renal pedicle,and shorten operation time,reduce postoperative complications.