Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Although computational approaches have been complementing high-throughput biolog-ical experiments for the identification of functional regions in the human genome,it remains a great challenge to systematically decipher interactions between transcription factors(TFs)and regulatory elements to achieve interpretable annotations of chromatin accessibility across diverse cellular con-texts.To solve this problem,we propose DeepCAGE,a deep learning framework that integrates sequence information and binding statuses of TFs,for the accurate prediction of chromatin acces-sible regions at a genome-wide scale in a variety of cell types.DeepCAGE takes advantage of a den-sely connected deep convolutional neural network architecture to automatically learn sequence signatures of known chromatin accessible regions and then incorporates such features with expres-sion levels and binding activities of human core TFs to predict novel chromatin accessible regions.In a series of systematic comparisons with existing methods,DeepCAGE exhibits superior perfor-mance in not only the classification but also the regression of chromatin accessibility signals.In a detailed analysis of TF activities,DeepCAGE successfully extracts novel binding motifs and mea-sures the contribution of a TF to the regulation with respect to a specific locus in a certain cell type.When applied to whole-genome sequencing data analysis,our method successfully prioritizes puta-tive deleterious variants underlying a human complex trait and thus provides insights into the understanding of disease-associated genetic variants.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.

Objective To evaluate the efficacy of ultrasound-guided great auricular nerve (GAN)block combined with general anesthesia for middle ear microsurgery in adult patients.Methods Sixty-four adult patients of both sexes,aged 18-60 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective middle ear microsurgery,were assigned into 2 groups (n =32 each) using a random number tabte:GAN block combined with general anesthesia group (group GANB+G) and general anesthesia group (group G).Patients received GAN block with 0.25％ ropivacaine 2 ml using ultrasoundguided in-plane technique before anesthesia induction in group GANB+G.Anesthesia induction and maintenance protocols (IV infusion of propofol and target-controlled infusion of remifentanil) were similar in two groups.Analgesia was performed with sufentanil,flurbiprofen axetil or parecoxib sodium after operation to maintain visual analog scale score ＜4 within 48 h after operation.The infusion duration and consumption of propofol and remifentanil,requirement for postoperative analgesia and occurrence of postoperative nausea and vomiting were recorded.Results Compared with group G,the consumption of remifentanil was significantly reduced,and the requirement for postoperative analgesia and incidence of postoperative nausea and vomiting were decreased in group GANB + G (P ＜ 0.05 or 0.01).Conclusion Ultrasound-guided GAN block combined with general anesthesia provides better analgesic efficacy in the the perioperative period in adult patients undergoing middle ear microsurgery.

Objective To determine the clinical features and the factors affecting the recurrence of ovarian borderline epithelial tumors. Methods A retrospective data of 112 cases with ovarian borderline epithelial tumors admitted in General Hospital of Tianjin Medical University from 2000 to 2015 were analyzed. Results The average age was (50.59±16.90) years in 112 patients with FIGO stageⅠof 102 (91.07%) patients, stageⅡof 4 (3.57%) and stageⅢof 6 (5.36%). The serum tumor marker (CA125) was examined in 102 patients, and 27 cases with the elevated indicator (26.47%). Surgical treatment was performed in 112 patients. Younger patients were more likely to choose conservative surgery. Ninety-seven patients were followed up, and 5 of them relapsed. Non fertility preserving surgery was performed in patients with recurrence. The recurrence rates of patients with different clinical pathological factors were compared. The recurrence rate was higher in patients with micro infiltration than that of patients without micro infiltration [37.50%(3/8) vs. 2.25%(2/89), P=0.004]. And the recurrence rate was higher in patients with microemulsion type borderline serous tumor than that of patients with non-papillary tumors [40.00%(2/5)vs. 0(0/41),P=0.019]. Seven patients underwent conservative surgery had normal spontaneous pregnancy. Conclusion The fertility-sparing surgery can be used as the treatment procedures for young patients, which is safe and effective. It is necessary to be on alert of recurrence for the cases with micropapillary pattern, and microinvasive tumor.

Objective To detect the important parameters of three dimensional structure of the aortic annulus by using real time three dimensional transesophageal echocardiograhy (RT 3D TEE) and analyse morphological and physiological characteristics , in order to establish simplified model of aortic valve and provide references for designing aortic annulus .Methods A total of 95 ca‐ses of healthy individuals carrying out RT 3D TEE were selected ,and the images of total volume of aortic root were collected .The important parameters of three dimensional aortic valve in four cardiac cycles ,including sinus tube junction(S) ,distance between ad‐jacent valve junction(L ,R and N) ,diameter of the circumcircle of triangle(J) ,aortic annulus height(H) ,long diameter(A) ,short di‐ameter(B) and eccentricity ratio (B/A) of the aortic valve ,were measured by using the QLAB7 .0 software .In the 3D imaging ,the extending relationship between the bottom of aortic valve and aortic annulus was analysed ,the structural characteristics of the aortic valve were simplified ,and the model was established .Results The values of the parameters measured at the end‐diastole were as follows :sinus tube junction (26 .3 ± 3 .3)mm ,three‐dimensional aortic annulus height(12 .4 ± 1 .9)mm ,aortic valve long diameter and short diameter (25 .9 ± 2 .7)mm and (19 .8 ± 2 .0)mm ,adjacent valve junction distance(L ,R and N) all was(21 .6 ± 2 .5)mm . These three structures approximately formed an equilateral triangle .The values of the adjacent cycle time ,the change of sinus tube junction ,distance between adjacent valve junction ,aortic annulus height and long diameter were compared ,and there was no statisti‐cal significant differences(P>0 .05) ,while statistically significant differences were found in the aortic valve short diameter and long short diameter between those at the end‐diastole and those at the medium‐systole(P<0 .01) .Conclusion RT 3D TEE can accu‐rately measure the size of each part of the aortic valve and display its shape and change ,which contribute to simplifying and recon‐structing the aortic annlus .

Aorta ; abnormalities ; Child ; Heart Defects, Congenital ; diagnosis ; Heart Ventricles ; abnormalities ; Humans ; Male

Objective To explore the clinicalpathological characteristics of Lynch syndrome associated ovarian cancer.Methods Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan.2004 and Jan.2011,among which 10 patients( LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam Ⅱ criteria.One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group).Results Lynch syndrome associated ovarian cancer accounted for 3.8％ ( 10/260),the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7％ ( 10/115 ).Mean age at time of diagnosis in LS group was (46 ±7) years,significantly earlier than that in sporadic group [ (56 ±11 ) years,P ＜ 0.05 ].There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics ( FIGO ) stage ( P ＞ 0.05 ).Most of the tissue differentiation in LS group were well or moderate differentiated,there was statistical difference between the two groups(9/10 vs.55％,P ＜0.05).The 3-year and 5-year survival rate in LS group were 87.5％ and 52.5％respectively,compared with 55.4％and 22.7％ in sporadic group(all P＜0.05).Conclusion Compared with sporadic ovarian cancer,Lynch syndrome associated ovarian cancer is more likely present as the clinicalpathological characteristics of early age of onset,serous adenocarcinoma,lower grade and better prognosis.