Methyltransferase WTAP aggravates hypoxia/reoxygenation-induced myocardial cell injury by regulating the expression of activator of transcription 4 / 中华危重病急救医学

Objective:To investigate the regulatory role of Wilms tumor 1-associating protein (WTAP) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its molecular mechanism.Methods:① Experiment Ⅰ: H9C2 cardiomyocytes were divided into blank control group and H/R model group. H/R was used to induce myocardial ischemia/reperfusion (I/R) injury model in H9C2 cells. The blank control group was not treated. N6-methyladenosine (m6A) RNA methylation assay kit was used to detect the level of m6A. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect the mRNA and protein expression levels of methyltransferases [WTAP, methyltransferase-like proteins (METTL3, METTL14)], respectively. ② Experiment Ⅱ: H9C2 cardiomyocytes were divided into blank control group, H/R+sh-NC group, and H/R+sh-WTAP group. sh-WTAP was transfected to knock down the expression of WTAP in H/R+sh-WTAP group, and the model establishment method in the other groups was the same as experimentⅠ. At 48 hours after transfection, the apoptosis rate of cells was detected by flow cytometry. The protein expressions of WTAP, activated caspase-3, activated poly (ADP-ribose) polymerase (PARP), activating transcription factor 4 (ATF4), proline-rich receptor-like protein kinase (PERK), phosphorylated PERK (p-PERK) and CCAAT/enhancer-binding protein homologous protein (CHOP) were detected by Western blotting. The positive expression of ATF4 was observed by immunofluorescence staining. ③ Experiment Ⅲ: H9C2 cardiomyocytes were divided into blank control group, H/R+sh-NC group, H/R+sh-WTAP group and H/R+sh-WTAP+ATF4 group. The overexpression plasmid ATF4 was transfected into H9C2 cardiomyocytes, and the modeling method of the other groups were modeled the same as experimentⅡ. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the protein expressions of ATF4, CHOP, activated caspase-3 and activated PARP.Results:① ExperimentⅠ: the methylation level of m6A in the H/R group was significantly higher than that in the blank control group. RT-qPCR results showed that the gene expressions of METTL3, METTL14 and WTAP in the H/R model group were significantly higher than those in the blank control group, and WTAP was the most significantly up-regulated. Western blotting results showed the same trend. These results suggested that the expression level of methyltransferase WTAP is significantly up-regulated in H/R-induced cardiomyocytes. ②Experiment Ⅱ: the apoptosis level in H/R+sh-WTAP group was significantly lower than that in H/R+sh-NC group [(14.16±1.58)% vs. (24.51±2.38)%, P < 0.05]. Western blotting results showed that the protein expressions of WTAP, activated caspase-3, activated PARP, p-PERK, ATF4 and CHOP in the H/R+sh-WTAP group were significantly lower than those in the H/R+sh-NC group. Fluorescence microscopy results showed that the ATF4 positive signal in the H/R+sh-WTAP group was significantly weaker than that in the H/R+sh-NC group [(19.36±1.81)% vs. (32.83±2.69)%, P < 0.01]. The above results suggested that knockdown of WTAP could inhibit H/R-induced cardiomyocyte apoptosis and endoplasmic reticulum stress. ③ Experiment Ⅲ: the apoptosis level of H/R+sh-WTAP+ATF4 group was significantly higher than that of H/R+sh-WTAP group [(26.61±2.76)% vs. (17.14±0.87)%, P < 0.05]. Western blotting results showed that the protein expressions of ATF4, CHOP, activated caspase-3 and activated PARP in the H/R+sh-WTAP+ATF4 group were significantly higher than those in the H/R+sh-WTAP group. These results suggested that overexpression of ATF4 reversed the inhibitory effect of sh-WTAP on endoplasmic reticulum stress and apoptosis in H/R-induced cardiomyocytes. Conclusion:Methyltransferase WTAP could regulate ATF4 expression, mediate cell apoptosis and endoplasmic reticulum stress, and promote H/R-induced myocardial cell injury.

Embryo-fetal developmental toxicity and toxicokinetics of fluoropezil in New Zealand rabbits / 中国药理学与毒理学杂志

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

The directionality of measurement bias: a directed acyclic graph-based structural perspective / 中华流行病学杂志

Measurement bias (MB) has been described in causal structures but is still not entirely clear. In practice, the correctness of substitution estimate (SE) of effect is a prerequisite for causal inference, usually based on a bidirectionally non-differential misclassification between the measured exposure and the measured outcome. Based on a directed acyclic graph (DAG), this paper proposes a structure for the single-variable measure, where its MB is derived from the choice of an imperfect, "input/output device-like" measurement system. The MB of the SE is influenced both by the measurement system itself and by factors outside the measurement system: while the independence or dependence mechanism of the measurement system still ensures that the MB of the SE is bidirectionally non-differential; however, the misclassification can be bidirectionally non-differential, unidirectionally differential, or bidirectionally differential resulted from the factors outside the measurement system. In addition, reverse causality should be defined at the level of measurement, where measured exposures can influence measured outcomes and vice versa. Combined with temporal relationships, DAGs help elucidate MB's structures, mechanisms, and directionality.

Association between gestational diabetes mellitus and preterm birth subtypes / 中华流行病学杂志

Objective: To investigate the association between gestational diabetes mellitus (GDM) and preterm birth subtypes. Methods: Based on the cohort of pregnant women in Anqing Prefectural Hospital, the pregnant women who received prenatal screening in the first or second trimesters were recruited into baseline cohorts; and followed up for them was conducted until delivery, and the information about their pregnancy status and outcomes were obtained through electronic medical record system and questionnaire surveys. The log-binomial regression model was used to explore the association between GDM and preterm birth [iatrogenic preterm birth, spontaneous preterm birth (preterm premature rupture of membranes and preterm labor)]. For multiple confounding factors, the propensity score correction model was used to compute the adjusted association. Results: Among the 2 031 pregnant women with a singleton delivery, the incidence of GDM and preterm birth were 10.0% (204 cases) and 4.4% (90 cases) respectively. The proportions of iatrogenic preterm birth and spontaneous preterm birth in the GDM group (n=204) were 1.5% and 5.9% respectively, while the proportions in non-GDM group (n=1 827) were 0.9% and 3.2% respectively, and the difference in the proportion of spontaneous preterm birth between the two groups was significant (P=0.048). Subtypes of spontaneous preterm were further analyzed, and the results showed that the proportions of preterm premature rupture of membranes and preterm labor in the GDM group were 4.9% and 1.0% respectively, while the proportions in the non-GDM group were 2.1% and 1.1% respectively. It showed that the risk of preterm premature rupture of membranes in GDM pregnant women was 2.34 times (aRR=2.34, 95%CI: 1.16-4.69) higher than that in non-GDM pregnant women. Conclusions: Our results showed that GDM might increase the risk of preterm premature rupture of membranes. No significant increase in the proportion of preterm labor in pregnant women with GDM was found.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells / 生理学报

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

Differential diagnosis of benign and malignant breast calcification by quantitative measurement of gray value on contrast-enhanced spectral mammography / 中华放射学杂志

Objective:To investigate the value of gray value (GV) measurement of subtraction images in contrast-enhanced spectral mammography (CESM) in the differential diagnosis of breast benign and malignant calcification.Methods:This was a retrospective study. A total of 95 patients received CESM only with mammographic calcifications without any associated mass or distortions from March 2017 to July 2021 in Peking University Cancer Hospital were enrolled. The patients were all female with an average age of 34-76(48±7) years. The craniocaudal (CC) projection of bilateral breasts was obtained prior to the mediolateral-oblique (MLO) projection. Two radiologists were asked to independently review the images to diagnose the calcification as either benign or malignant based on the presence of enhancement on subtracted imaging. GV of the calcification and background parenchyma including breast parenchyma tissue, the pectoralis major muscle and subcutaneous fatty tissue were measured by another two radiologists. The difference of lesion to background parenchyma GV (D GV) and lesion to background parenchyma gray value ratio (DR GV) were calculated. The consistency of observers was compared using the Kappa statistic. The stability of GV was evaluated with coefficient of variation. Differences of GV, D GV and DR GV between benign and malignant calcification were compared using t test or Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of GV in differentiating benign from malignant calcification. Comparisons between diagnostic efficacies were performed using χ 2 tests. Results:Totally 97 calcification (35 malignant and 62 benign) from 95 patients were enrolled. The consistency and stability of GV values on MLO and CC projections measured by two physicians were high. The GV, D GV and DR GV of malignant calcification were significantly higher than those of the benign lesions ( P<0.05). The area under the ROC curve for the differential diagnosis of benign and malignant calcification by GV in the MLO and CC positions was 0.799 and 0.843, respectively. Threshold of calcified area GV=2015.5 in CC position, its diagnostic accuracy was 76.8%, which was similar to the subjective diagnosis of radiologists (82.1%, 78/95, P>0.05). Conclusion:Quantitative GV on subtracted imaging of CESM can differentiate benign from malignant breast calcification, especially on craniocaudal projection.

Clinical Characteristics and Survival Analysis of Carbapenem-Resistant Pseudomonas Aeruginosa Colonized or Infected Patients with Hematological Disorders / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical characteristics and impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) colonized or infected patients with hematological disorders in order to provide evidence for the prevention and treatment of CRPA.@*METHODS@#The patients who were colonized or infected with CRPA in the Department of Hematology of The First Affiliated Hospital of Zhejiang Chinese Medical University from January 2020 to March 2021 were selected as the research subjects, the clinical data such as hospitalization time, primary disease treatment regimen, granulocyte count, previous infection and antibiotic regimen of these patients were analyzed, meanwhile, antibiotic regimen and efficacy during CRPA infection, 30-day and long-term survival were also analyzed.@*RESULTS@#A total of 59 patients were included in this study, and divided into CRPA infection group (43 cases) and CRPA colonization group (16 cases). Univariate logistic regression analysis showed that ECOG score (P =0.003), agranulocytosis (P <0.001), and exposure to upper than 3rd generations of cephalosporins and tigecycline within 30 days (P =0.035, P =0.017) were the high-risk factors for CRPA infection. Multivariate logistic regression analysis showed that ECOG score of 3/4 ( OR=10.815, 95%CI: 1.260-92.820, P =0.030) and agranulocytosis ( OR=13.82, 95%CI: 2.243-85.176, P =0.005) were independent risk factors for CRPA infection. There was a statistically significant difference in cumulative survival rate between CRPA colonization group and CRPA infection group ( χ2=14.134, P < 0.001). Kaplan-Meier survival analysis showed that the influencing factors of 30-day survival in patients with CRPA infection were agranulocytosis (P =0.022), soft tissue infection (P =0.03), and time of hospitalization before CRPA infection (P =0.041). Cox regression analysis showed that agranulocytosis was an independent risk factor affecting 30-day survival of patients with CRPA infection (HR=3.229, 95%CI :1.093-3.548, P =0.034).@*CONCLUSIONS@#Patients with hematological disorders have high mortality and poor prognosis after CRPA infection. Bloodstream infection and soft tissue infection are the main causes of death. Patients with high suspicion of CRPA infection and high-risk should be treated as soon as possible.

A single-cell landscape of triptolide-associated testicular toxicity in mice / 药物分析学报

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

Systematic analysis of MYB transcription factors related to the geniposide biosynthesis in Gardenia jasminoides Ellis based on whole genome / 药学学报

MYB transcription factors are involved in the regulation of various secondary metabolites biosynthesis. Gardenia jasminoides Ellis is the commonly used Chinese herbal medicine, and its main active ingredient is geniposide. Here, leaves and flower buds at different developmental stages of G. jasminoides were used to explore MYB transcription factors related to geniposide biosynthesis based on genome and transcriptome analysis. Transcriptome data analysis showed that, different from the expression of the common pathway genes for terpenoid biosynthesis, the expression level of genes in the specific pathway of geniposide biosynthesis was significantly higher in flower buds than in leaves, which was the same as the organ accumulation pattern of this component. And the promoter regions of geraniol synthase, iridoid synthase and geniposidic acid methyltransferase involved in the specific pathway all contained multiple MYB-binding sites. A total of 105 MYB transcription factors were obtained by annotating the coding genes of G. jasminoides, which were divided into 68 1R-MYB, 33 R2R3-MYB, 3 3R-MYB and 1 atypical MYB transcription factor according to the number of conserved domain. Based on the analysis of phylogenetic tree and quantitative real-time PCR, three candidate MYB transcription factors related to geniposide biosynthesis were selected, including potential positive regulation factor GjMYB23 and negative regulation factors GjMYB31 and GjMYB73. The results of this study will lay a foundation for searching the regulation of geniposide biosynthesis and further analysis of the quality formation mechanism of G. jasminoides, so as to promote the breeding of excellent varieties of G. jasminoides.

Effect of insular involvement on the outcomes of patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the effect of insular involvement on the outcomes of patients with acute anterior circulation ischemic stroke.Methods:Patients with acute anterior circulation ischemic stroke admitted to the Department of Neurology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University from January 2015 to December 2020 were retrospectively included. Demographic data, vascular risk factors, clinical and laboratory data, as well as treatment and outcomes were collected. Firstly, the correlation between the insular involvement and the outcomes was investigated, and then the bootstrap method was used to clarify the mediating role of infarct volume between the insular involvement and the poor outcomes.Results:A total of 450 patients with acute anterior circulation ischemic stroke were enrolled, among whom 79 cases (17.6%) had insular involvement and 41 (9.1%) had left insular involvement. There were 111 (24.7%) with poor outcomes, including 5 (1.1%) died. Compared to the non-insular involvement group, the insular involvement group had a higher proportion of patients with atrial fibrillation, shorter onset to door time, higher neutrophil-to-lymphocyte ratio (NLR), higher National Institutes of Health Stroke Scale (NIHSS) score at admission, larger infarct volume, and higher proportion of patients with poor outcomes (all P<0.05). In addition, patients with left insular involvement were younger than those with right insular involvement, had a higher baseline NIHSS score, a lower proportion of patients with minor stroke (NIHSS score ≤8), and had a longer onset to door time (all P<0.05). Compared to the good outcome group, the poor outcome group was older, with a higher proportion of female patients, higher systolic blood pressure, blood glucose, NLR, and NIHSS scores at admission, larger infarct volume, and a higher proportion of patients with insular involvement (all P<0.05). Mediation analysis suggested that the mediating effect of infarct volume between the insular involvement and the poor outcomes was significant (95% confidence interval 0.033-0.230; P=0.008). Conclusions:insular involvement in patients with acute anterior circulation ischemic stroke is associated with the poor outcomes, and this association may be mediated by infarct volume. Patients with left insular involvement may have more severe symptoms than those with right insular involvement, but there is no significant difference in the outcomes.

Analysis on epidemiological characteristics of dengue fever and E gene evolution of dengue virus in Guangzhou, 2020 / 中华流行病学杂志

Objective: To assess the incidence of dengue fever and E gene evolution of dengue virus in Guangzhou in 2020 and understand the local epidemiological characteristics of dengue fever and spreading of dengue virus. Methods: The information of dengue fever cases in Guangzhou in 2020 was collected from Notifiable Infectious Disease System of Chinese Center for Disease Control and Prevention Information System. Serum samples from the cases were detected by real-time PCR. The E gene was sequenced and analyzed. Maximum likelihood phylogenetic trees were constructed using software MEGA 5.05. The statistical analysis was conducted using software SPSS 20.0. Results: A total of 33 dengue fever cases were reported in Guangzhou in 2020, including 31 (93.94%) imported cases and 2 (6.06%) local cases. Compared with the data during 2016 to 2019, the number of cases, overall incidence and local incidence all decreased with statistically significant differences (all P<0.05). The imported cases from Southeast Asia constituted 90.32% (28/31) of imported cases. The E gene sequences and the phylogenetic trees of imported and local cases demonstrated close relationship with the virus sequences from Southeast Asian, and they were less homologous with the sequences of dengue virus isolated in Guangzhou in previous years. Conclusions: The incidence of dengue in Guangzhou in 2020 was significantly affected by the imported cases, especially those from Southeast Asian countries. The study result demonstrated that dengue fever was not endemic in Guangzhou and it was caused by imported ones.

Analysis of clinical characteristics and prognosis of 4 264 patients with asymptomatic and mild novel coronavirus infections in Shanghai / 中华危重病急救医学

Objective:To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment.Methods:Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed.Results:A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37∶1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). Conclusions:The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.

Knocking-down Synaptotagmin 1 Attenuated Colitis via Suppressing the IL-6/STAT3 Signaling Pathway / 中国生物化学与分子生物学报

Synaptotagmin 1 (Sytl) is a member of the Synaptotagmin family and plays a role in neurotransmitter vesicle transport and exoeytosis. It has been reported that Sytl appears to be expressed in the intestinal epithelium, but the biological function of Sytl in colitis remains poorly understood. This study aimed to investigate the effects of Sytl in the inflammatory response and intestinal epithelial regeneration in colitis using Sytl transgenic mice and dextran sulfate sodium (DSS)-induced ulcerative colitis mode. qRT-PCR and Western blotting were employed to analyze the dynamic changes of Sytl in colitis. H&E staining, immunostaining and Western blotting were used to explore the roles of Sytl in the inflammatory response and in the regeneration and repair of intestinal epithelium in colitis. The results showed that the expression level of Sytl was indeed high in the colonic epithelium of wild-type mice and the intestinal epithelial cells of the adjacent tissues of colorectal cancer patients. Consistently, DSS-induced inflammation progressively resulted in marked upregulation of Sytl in the colon (P<0.01). In DSS-induced colitis, both the body weight loss and colonic shortening were dampened in Sytl loss-of-function mice compared with the control group (P < 0.05), while the number of regenerated crypts and Ki67 proliferating cells were also increased (P<0.01). Additionally, there were less infiltration of CD45 immune cells and F 4/80 macrophages and the expression of pro-inflammatory cytokines IL-6, TNFα and I L l-β, which were related with the severity of inflammation in the inflammatory bowel disease (I B D), were significantly decreased after Sytl deletion (P<0.05). Immunohistochemistry staining and Western blotting results further showed that IL-6 and p-STAT3 was significantly downregulated in Sytl knockdown mice (P<0.05). Taken together, these results suggested that knocking-down of Sytl may improve colitis by inhibiting the IL6/STAT3 signaling pathway.

Effect and Mechanism of Xiangsha Liujunzi Tang on Lipid Deposition in Liver of ApoE-/- AS Mice by Affecting Long Noncoding RNA-HC/miR-130b and to Regulate Cholesterol Metabolism / 中国实验方剂学杂志

Objective:To investigate the mechanism of Xiangsha Liujunzi Tang in improving liver lipid deposition in ApoE^-/- atherosclerotic （AS） mice by affecting long noncoding RNA-HC （Lnc-HC）/microRNA-130b （miR-130b） in the regulation of cholesterol metabolism. Method:Totolly 10 C57BL/6J mice were selected as normal controls， and 30 healthy ApoE^-/- mice fed with high fat diet for 12 weeks were then randomly divided into the model group， Xiangsha Liujunzi Tang group（19.12 g·kg^-1·d^-1） and simvastatin group（2.275 mg·kg^-1·d^-1）， with gavage administration for 4 weeks. The serum lipid level of mice was detected by automatic biochemistry analyzer， and the histopathological changes of liver cells were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect expression of long noncoding RNA-HC， and miR-130b. Real-time PCR and Western blot assay were used to detect gene and protein expression of peroxisome proliferator-activated receptor gamma （PPAR<italic>γ</italic>）， liver X receptor （LXR）， ATP-binding cassette transporters A1 （ABCA1）， ATP-binding cassette transporters G1 （ABCG1）， ATP-binding cassette transporters G5 （ABCG5）， and ATP-binding cassette transporters G8 （ABCG8）. Result:Compared with the normal control group， the mice in the model group showed abnormal blood lipids， larger liver cells， obvious fat vacuoles， significantly increased expression of Lnc-HC， miR-130b in liver， and significantly decreased gene and protein expression of PPAR<italic>γ</italic>， LXR， ABCA1， ABCG1， ABCG5， and ABCG8 in mice liver （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the abnormal blood lipid levels of the mice in the Xiangsha Liujunzi Tang group and the simvastatin group were improved， and the number of fatty vacuoles of liver cells was significantly reduced， the expression of liver Lnc-HC， miR-130b in Xiangsha Liujunzi Tang group decreased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01）， the gene and protein levels of liver PPAR<italic>γ</italic>， ABCA1， ABCG1， ABCG5， ABCG8 in mice of the Xiangsha Liujunzi Tang group and the simvastatin group showed an upward trend. Among them， the gene and protein expression of LXR protein in the liver of the Xiangsha Liujunzi Tang group was significantly up-regulated （<italic>P</italic><0.05）. Conclusion:Xiangsha Liujunzi Tang may improve the lipid deposition in the liver of ApoE^-/-AS mice by affecting Lnc-HC/miR-130b to regulate the cholesterol metabolism process mediated by PPAR<italic>γ</italic>， thus playing a role in preventing and treating AS.

The predictive value of red blood cell distribution width in predicting the prognosis of patients with Extracorporeal Membrane Oxygenation / 中华急诊医学杂志

Objective:To explore the predictive value of Red Blood Cell Distribution Width (RDW) in predicting the prognosis of patients with Extracorporeal Membrane Oxygenation (ECMO).Methods:The clinical data of patients undergoing ECMO admitted to Intensive Care Unit of Sichuan Provincial People’s Hospital from January 2015 to January 2020 were retrospectively analyzed. Patients were divided into the survival group and death group according to the prognosis during ICU hospitalization. The patients' basic data , acute physiology and chronic health score system Ⅱ (APACHE Ⅱ), RDW and activated partial thromboplastin time (APTT) at 72 hours after treatment with ECMO were compared between the two groups. Univariate and Logistic regression multivariate analyses were used to analyze the prognostic factors of patients with ECMO, predictive models and death warning scores were established. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficacy of RDW and death warning scores for the prognosis of patients with ECMO.Results:A total of 71 patients with ECMO who met the inclusion criteria were included, including 38 patients in the death group and 33 patients in the survival group. The age, APACHE-Ⅱscore, 72 h RDW and 72 h APTT in the death group were higher than those in the survival group. Respectively, the hospitalization time of ICU in the death group was significantly lower than that in the survival group ( P< 0.05). Logistic regression analysis showed that APACHE-Ⅱscore ( OR=1.117, P=0.047)、72 h RDW( OR=1.102, P=0.029) and 72 h APTT ( OR=1.049, P=0.029) were independent risk factors for death in patients with ECMO. ROC curve analysis showed that the area under ROC curve (AUC) of the APACHE-Ⅱ, score 、72 h RDW and 72 h APTT were 0.691, 0.691 and 0.632( P<0.05), Respectively, the combined AUC was 0.764, the sensitivity was 0.526, and the specificity was 0.909. The death warning score of patients with ECMO was established according to the Predictive model , which is less than 2 points with low risk of death and more than 2 points with high risk of death. The area under the ROC curve of death warning score is 0.8, the sensitivity is 0.607 and the specificity is 0.923. Conclusions:The RDW at 72 hours after treatment with ECMO has a good value in predicting the prognosis of patients with ECMO. Besides, a greater predictive value for the prognosis of patients with ECMO by combining 72 hours RDW, 72 hours APTT with APACHE-Ⅱscore than that of any separate indicator.

Experimental study on the distribution of 99Tc m-MDP in the repair of femoral bone injury in rabbits / 中华核医学与分子影像杂志

Objective:To investigate the distribution of 99Tc m-methylene diphosphonate (MDP) at different stages of bone injury repair. Methods:A total of 30 rabbit models of femur injury were established by the method of electric drill and perforation of femur. According to the different stages of bone injury repair (at 1, 2 and 3 week), rabbits were divided into group A, B and C ( n=10 each group). Femoral SPECT/CT imaging was performed on the last day of different stages of bone injury repair to obtain radioactivity counts in the region of interest (ROI) on the test side and control side and to calculate target/background ratio (T/B). The light intensity of 3 groups was analyzed by phosphor screen imaging and the distribution of 99Tc m-MDP in bone cells was observed by autoradiography. One-way analysis of variance and paired t test were used to analyze the data. Results:The T/B values of group A, B and C were 1.16±0.14, 1.39±0.23 and 1.18±0.10, respectively ( F=5.83, P<0.01). There were significant differences of the maximum radiation count between the test side (50.00±12.45, 59.50±12.83 and 55.10±9.26) and the control side (43.20±9.57, 50.00±12.30 and 44.30± 6.50) in group A, B and C ( t values: 3.24, 2.28 and 5.77, all P<0.05). There were significant differences in the light intensity of bone specimens in group A, B and C by phosphor screen imaging (37 324.67±6 481.50, 60 950.33±9 781.72 and 43 905.00±4 957.92; F=8.25, P=0.02). 99Tc m-MDP were deposited in both intracellular and extracellular during different stages of bone repair in osteocytes and osteoblasts under autoradiography. Conclusion:At different stages of bone injury repair, the concentration of 99Tc m-MDP is significantly distributed, suggesting that there are other ways of concentration mechanism of 99Tc m-MDP in bone tissue besides the chemical adsorption with hydroxyapatite.

Expert consensus on Tongsaimai Tablets/Capsules in treatment of peripheral vascular diseases in clinical practice / 中国中药杂志

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.

Comparison on radiation dose of contrast-enhanced mammography and full-field digital mammography / 中国医学影像技术

Objective To compare breast radiation dose between contrast-enhanced mammography (CEM) and full-field digital mammography (FFDM), and to explore the correlation of breast radiation dose with gland compression thickness. Methods The average gland dose (AGD) of FFDM and CEM were compared through phantom experiment on the same mammography device. Totally 102 patients with breast disease underwent CEM (CEM group), while other 104 underwent FFDM (FFDM group) on the same machine, and AGD and gland compression thickness were recorded. Based on the 5th breast imaging-reporting and data system (BI-RADS) of American college of radiology (ACR), the breasts were divided into dense glands and non-dense glands. The differences of AGD and gland compression thickness were compared between 2 groups and among different types of glands, and the correlations of AGD and gland compression thickness were analyzed. Results AGD of low-energy CEM and FFDM were similar in phantom experiment. There were 22 non-dense glands and 80 dense glands in CEM group, 39 non-dense glands and 65 dense glands in FFDM group. No significant difference in gland compression thickness was found between 2 groups (U=4 823.50, P>0.05). There was no statistical difference of the AGD in CEM group and AGD of FFDM group (U=5 249.50, P>0.05), while AGD of low energy CEM was lower than that of FFDM group (U=2 111.00, P0.05). The AGD of dense glands was higher than that of non-dense glands in FFDM group (U=846.50, P0.05). Conclusion The overall ADC of CEM was comparable to that of FFDM. The thinner the gland compression thickness is, the lower the radiation dose is. CEM had more advantageous for dense breasts than for non-dense glands.

Report of 15 cases of single-port video-assisted thoracoscopic surgery for pulmonary sequestration / 上海交通大学学报（医学版）

Objective: To investigate the feasibility of single-port video-assisted thoracoscopic surgery (VATS) for pulmonary sequestration. Methods: Fifteen cases with intralobar pulmonary sequestration in Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2014 to December 2018 were reviewed. All the cases had underwent lobectomy by single-port VATS, including 13 cases of left lower lobectomy and 2 cases of right lower lobectomy. Results: Pleural adhesion was found in 11 of the 15 cases. Lobectomy was successfully performed by single-port VATS in 12 cases. Three cases were transferred to multi-port VATS because of severe pleural adhesion. There was no case conversed to thoracotomy in the study. There was no mortality and complication during the perioperative period. For the 15 cases, the operation time was (96.7±27.8) min, the bleeding volume was (75.3±45.5) mL, the postoperative intubation was (5.2±2.0) d and the postoperative hospital stay was (6.2±2.2) d. Conclusion: Single-port VATS treatment for pulmonary sequestration is safe, effective and feasible.

Recent advances in the biotoxicity of silica nanoparticles / 医学研究生学报

Silica Nanoparticles (SiNPs) is widely used in many fields including antibacterial agent, molecular probe and drug delivery forits special physicochemical properties. Recently, the biosecurity of nano-materials has become a hot spot of research in toxicology due to special structure and functional activeness of nano-materials. This paper briefly summarized recent researchreports at home and abroadto review the toxicity of SiNPs on cells and animals, the factors for influencing the toxicity of SiNPs and the mechanisms underlying SiNPs biotoxicity, aiming to provide references for the development, application and biosecurity of SiNPs.