[Treatment of patent ductus arteriosus in very preterm infants in China].

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.

[Evolution and progress of surgical intervention strategies for acute pancreatitis].

Acute pancreatitis is one of the common surgical acute abdominal diseases. Since people first recognized acute pancreatitis in the middle of the nineteenth century, a diversified minimally invasive treatment model with standardization has been formed today. According to the main line of surgical intervention of acute pancreatitis treatment,this period can be roughly divided into five stages:exploration stage, conservative treatment stage, pancreatectomy stage, debridement and drainage of the pancreatic necrotic tissue stage, and minimally invasive treatment as the first choice led by the multidisciplinary team mode stage. Throughout history, the evolution and progress of surgical intervention strategies for acute pancreatitis cannot be separated from the progress of science and technology, the update of treatment concepts and the further understanding of the pathogenesis. This article will summarize the surgical characteristics of acute pancreatitis treatment at each stage to explain the development of surgical treatment of acute pancreatitis,to help investigate the development of surgical treatment of acute pancreatitis in the future.

[Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China].

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

[Comparison of three commercial photosensitizers for efficiency of inducing immunogenic cell death in anti-tumor immunotherapy].

OBJECTIVE: To compare 3 commercial immunogenic cell death (ICD) inducers, namely Chlorin e6 (Ce6), Neutral Red (NR), and Rose Bengal Sodium salt (RB), for their photosensitive properties, efficacy for photodynamic therapy (PDT) and ICD induction efficiency in antitumor immunotherapy. METHODS: Reactive oxygen species (ROS) probes were used to evaluate the photosensitivity of the 3 ICD inducers, and their capacity for inducing intracellular ROS production was evaluated using a DCFH-DA probe. The cytotoxicity and biocompatibility of the 3 photosensitizers were compared using a CCK-8 kit, and their ICD-inducing efficiency was assessed by detecting the levels of surface-exposed calreticulin (ecto-CRT), high mobility group protein 1 (HMGB1) and adenosine triphosphate (ATP). In the animal experiment, BALB/c mouse models bearing 4T1 cellderived subcutaneous tumor were given intratumoral injection of Ce6 or NR solution (30 µL, 5 mg/mL), followed 2 h later by white light irradiation for 10 min (400 mW/cm2). Body weight and tumor size changes of the mice were monitored, and the percentage of CD8+ T cells in the tumor and IFN-γ+ CD8+ T cells in the spleen were analyzed by flow cytometry 14 days after the treatment. HE and TUNEL staining was used to analyze tumor cell apoptosis in the mice. RESULTS: Among the 3 photosensitizers, Ce6 exhibited the strongest ROS-inducing capability and killing effect on the tumor cells. The results of ectoCRT, HMGB1 and ATP level detection all demonstrated a stronger ICD induction ability of Ce6. In the tumor-bearing mice, the tumor growth in Ce6 and NR groups was significantly inhibited after the treatment. The percentages of CD8+ T cells and IFN-γ+ CD8+ T cells were 12.7% and 7.1% in Ce6 group, respectively, significantly higher than those in NR group (6.1% and 2.8%, respectively; P < 0.05). HE and TUNEL staining revealed obvious tumor cell apoptosis in the tumor tissues in both Ce6 and NR groups, but the therapeutic effect was more prominent in Ce6 group. CONCLUSION: Among the 3 photosensitizers, Ce6 has the highest efficiency for inducing ROS production with the strongest PDT efficacy and ICD induction capability. Ce6 can also increase the number and function of CD8+ T cells in anti-tumor immunotherapy to initiate robust adaptive immune response.

Time resolved absolute extreme ultraviolet radiation measurement on the ENN XuanLong-50 spherical tokamak.

A plasma radiation measurement system for a wide spectral range, based on compact Absolute eXtreme UltraViolet (AXUV) silicon photodiodes, has been implemented on the newly constructed ENN XuanLong-50 (EXL-50) spherical tokamak. The system consists of two 16-channel AXUV16ELG arrays and one AXUV63HS1 single-cell detector mounted on ceramic sockets. The two arrays, facing toward the EXL-50 slim central post from two locations inside a top and a side ConFlat 400 port, have 32 view chords covering the interested plasma region in a poloidal cross section at toroidal 330°. The single-cell detector, seated on a retractable feedthrough, could be arranged flexibly with the help of an ultra-high vacuum compatible gate valve. The design details together with considerations on the EXL-50 specific engineering realities and physics requirements are described. Preliminary results from the EXL-50 2020 experimental campaign are presented.

Metabolomics Changes of Serum and Tissues in Mice Died of Acute Tetracaine Poisoning.

ABSTRACT: Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.

[Impact of iron deficiency on prognosis of heart failure patients with preserved ejection fraction].

Objective: To investigate the impact of iron deficiency (ID) on prognosis in heart failure patients with preserved ejection fraction (HFpEF). Methods: A total of 215 consecutive patients with HFpEF, who visited the cardiovascular outpatient department of Beijing Anzhen Hospital, were enrolled in this prospective study. The plasma ferritin level and transferin saturation were measured. Patients were divided into two groups: ID group and non-ID group. ID patients were further divided into absolute ID subgroup and functional ID subgroup. Patients were followed up to 1 year. The endpoints of the study were all-cause mortality and rehospitalization for heart failure (HF). The independent predictors of outcome were determined by Cox regression model. The quality of life of patients was evaluated at the end of the follow-up. Results: The age of this patient cohort was (67±8) years, 39.1% patients were male. The prevalence of ID was 54.4%. Within one year of follow-up, 37 patients (17.2%) died and 70 patients (32.6%) were rehospitalized for HF. Compared to non-ID group, patients in ID group were older, had higher heart rate, lower plasma hemoglobin level and estimated glomerular filtration rate (eGFR) value, had a higher prevalence of anemia and chronic kidney disease (P all<0.05). Kaplan-Meier curves showed that all-cause mortality and rehospitalization for HF in HFpEF patients with ID were higher than patients without ID, and prognosis was similar between patients with absolute ID and functional ID. Multivariable regression analysis showed that ID was an independent predictor for all-cause mortality and rehospitalization for HF in HFpEF patients. The of 6 minutes walking distance was shorter ((356.0±98.3)m vs. (389.2±94.3)m, P=0.023), and the value in Kansas city cardiomyopathy questionnaire was lower ((58.06±10.43) m vs. (61.51±11.64) m, P = 0.039) in patients with ID than patients without ID. Conclusion: In patients with chronic HFpEF, ID is an independent predictor for all-cause mortality and rehospitalization for HF at one year of follow-up, independent of the types of ID.

[Efficacy and safety of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma].

Objective: To evaluate the safety and efficacy of catheter ablation in patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma. Methods: Nine patients with new onset atrial arrhythmia and a prior history of left atrial myxoma, who received surgical myxoma excision and catheter ablation between September 2014 and November 2019, were included in the present study. Baseline characteristics, procedural parameters during catheter ablation, severe perioperative adverse events, recurrence rate of arrhythmia and clinical prognosis were analyzed. Kaplan Meier survival analysis was used to define the maintenance rate of sinus rhythm after catheter ablation in this patient cohort. Results: Nine patients were included. The average age was (55.8 ± 9.1) years old (3 male), there were 3 patients (3/9) with paroxysmal atrial fibrillation (PAF) and 6 patients (6/9) with atrial flutter or atrial tachycardia (AFL or AT). Ablation was successful in all patients, there were no perioperative complications such as stroke, pericardial effusion, cardiac tamponade, vascular complications or massive hemorrhage. During a mean follow-up time of 40.0 (27.5, 55.5) months, sinus rhythm was maintained in six patients (6/9) after the initial catheter ablation. The overall sinus rhythm maintenance rate was 2/3. In addition, 1 out of the 3 AF patients (1/3) developed recurrence of AF at 3 month after ablation, and 2 out of the 6 AFL or AT patients (2/6) developed late recurrence of AF or AFL (19 months and 29 months after ablation), two out of three patients with recurrent AFs or AFL received repeated catheter ablation and one patient remained sinus rhythm post repeat ablation. Meanwhile, there was no recurrence of atrial myxoma, no death, stroke, acute myocardial infarction and other events during the entire follow-up period. Conclusions: Catheter ablation is a safe and feasible therapeutic option for patients with new-onset atrial arrhythmia after surgical excision of left atrial myxoma.

[The classification and MR imaging of scapholunate ligament injuries].

Objective: To explore the MRI characteristics of injuries of scapholunate ligament (SLL), and provide imaging basis for the early diagnosis and treatment of the injuries. Methods: A total of 20 healthy volunteers without wrist injuries and 30 patients who complained dorsoradial-sided wrist pain and were highly suspected as the injury of SLL underwent the wrist magnetic resonance examination and X-ray examination in Beijing Jishuitan Hospital from January 2013 to September 2017.All subjects underwent anterior and lateral radiographs of the wrist joint and examination on coronal T(1)WI scan and PD-FS on 3 planes respectively in a prone position.Then the MRI characteristics of 20 healthy volunteers and 30 patients with SLL injuries that confirmed by operation were analyzed.According to the comparative analysis of normal anatomy and Geissler grades, the injuries were graded and MRI features of different types of injuries were analyzed.At last, imaging findings were compared with surgical results. Results: Twenty healthy volunteers without injuries showed mainly in low signal intensity on T(1)WI and PD-FS images.According to Geissler grades, there were 11 GradeⅠ injuries (5 had triangular fibrocartilage complex (TFCC) and SLL injuries and 1 had fracture of scaphoid and SLL injuries simultaneously), 8 GradeⅡ injuries (2 had TFCC and SLL injuries, 1 had TFCC, lunotriquetral ligament (LTL) and SLL injuries and 1 had distal radius fracture, TFCC and SLL injuries simultaneously), 7 Grade Ⅲ injuries (3 had TFCC and SLL injuries, 2 had fracture of scaphoid and SLL injuries and 1 had TFCC, LTL and SLL injuries simultaneously) and 4 Grade Ⅳ injuries (2 had TFCC and SLL injuries and 1 had fracture of scaphoid and SLL injuries simultaneously) among 30 patients.A tear can be confidently diagnosed when the ligament segment was absent or there was a fluidfilled discontinuity.A tear that involves 1 or 2 of the 3 segments (volar, proximal, or dorsal) of either the SLL was considered a partial tear, whereas a tear of all 3 segments was a complete tear. Conclusion: MRI can demonstrate the anatomy of interosseous ligaments accurately, evaluate and make the general grades of injuries.It is of significance for the early diagnosis and treatment protocols of the interosseous ligaments injuries.

Application of a triblock copolymer additive modified polyvinylidene fluoride membrane for effective oil/water separation.

A hollow fibre membrane was fabricated by blending polyvinylidene fluoride (PVDF) with a triblock copolymer additive polymer that has both hydrophilic and oleophobic surface properties. The novel membrane was characterized and examined for oil/water separation under various system conditions, including different cross-flow rate, feed temperature, trans-membrane pressure, and its rejection and cleaning efficiency, etc. By applying the membrane into the filtration of synthesized oil/water emulsion, the membrane constantly achieved an oil rejection rate of above 99%, with a relatively constant permeate flux varied in the range of 68.9-59.0 l m-2 h-1. More importantly, the fouling of the used membrane can be easily removed by simple water flushing. The membrane also demonstrated a wide adaptability for different types of real oily wastewater, even at very high feed oil concentration (approx. 115 000 mg l-1 in terms of chemical oxygen demand (COM)). Hence, the novel triblock copolymer additive-modified PVDF membrane can have a great prospect in the continuing effort to expand the engineering application of polymeric membranes for oily wastewater treatment.

Integration of molecules to construct the processes of conceptus implantation to the maternal endometrium.

During the peri-implantation period, ruminant conceptuses go through rapid elongation, followed by their attachment to the uterine endometrial epithelial cells, during which interferon-tau (IFNT), a trophectodermal cytokine required for the process of maternal recognition of pregnancy, is expressed in a temporal and spatial manner. On day 22 (day 0 = day of estrus), 2 to 3 d after the initiation of bovine conceptus attachment to the uterine epithelium, when IFNT production begins to subside, the expression of molecules related to epithelial-mesenchymal transition, zinc finger E-box binding homeobox 1, snail family transcriptional repressor 2, N-cadherin, and vimentin was found in the trophectoderm. Through the use of in vitro coculture system with bovine trophoblast CT-1 and endometrial epithelial cells, a series of experiments have been conducted to elucidate mechanisms associated with the regulation of IFNT gene transcription and conceptus implantation, including epithelial-mesenchymal transition processes. Expression of IFNT, both up- and downregulation, during the peri-implantation period is tightly controlled. Cytokines and cell adhesion molecules such as epidermal growth factor, basic fibroblast growth factor, transforming growth factor beta, activin A, L-selectin-podocalyxin, and vascular cell adhesion molecule 1-integrin α4 expressed in utero all contribute to the initiation of epithelial-mesenchymal transition in the trophectoderm. These results indicate that conceptus implantation to the uterine endometrium proceeds while elongated conceptuses and endometria express cell adhesion molecules and their receptors, and the trophectoderm experiences epithelial-mesenchymal transition. Data accumulated suggest that while the conceptus and the endometrial epithelium adhere, trophectodermal cells must gain more flexibility for binucleate and possibly trinucleate cell formation during the peri-implantation period, and that understanding and constructing the conditions throughout implantation processes is key to improving ruminants' fertility.

Combination curcumin and (-)-epigallocatechin-3-gallate inhibits colorectal carcinoma microenvironment-induced angiogenesis by JAK/STAT3/IL-8 pathway.

Tumor microenvironment has a crucial role in cancer development and progression, whereas the mechanism of how it regulates angiogenesis is unclear. In this study, we simulated the colorectal carcinoma microenvironment by conditioned medium (CM) of colorectal carcinoma cell lines (SW620, HT-29, HCT116) supernatant or colorectal carcinoma tissue homogenate supernatant to induce normal endothelial cells (NECs). We found that colorectal carcinoma CM promoted tumor angiogenesis by coercing NECs toward tumor endothelial cells (TECs) with the activation of the JAK/STAT3 signaling pathway. Antibody array analysis showed HT-29 supernatant contained numerous angiogenesis-related proteins, especially IL-8. Interestingly, the production of IL-8 in NECs induced by HT-29 CM was also increased. We also verified the crucial role of IL-8 in promoting the CM-induced angiogenesis, as IL-8 repression by neutralizing antibody abolished the transition of NECs toward TECs. Curcumin and (-)-epigallocatechin-3-gallate (EGCG) are broadly investigated in cancer chemoprevention. However, poor bioavailability hurdles their application alone, and the mechanism of their anti-angiogenesis still need to be illuminated. Here, we found that curcumin combination with EGCG attenuated the tumor CM-induced transition of NECs toward TECs by inhibiting JAK/STAT3 signaling pathway. Furthermore, the combination of curcumin and EGCG markedly reduced tumor growth and angiogenesis in the colorectal carcinoma PDX mouse model, and the combined anti-angiogenic effect was better than that of curcumin or EGCG alone. Taken together, our findings provide a new mechanism of tumor angiogenesis, and the combination of curcumin and EGCG represents a potential anti-angiogenic therapeutic method for colorectal carcinoma.

[MRI anatomy and injury of the lateral collateral ligaments of ankle].

Objective: To explore the MRI features of the lateral collateral ligament injuries of the ankle and determine the value MRI in diagnosing the ligament injuries of the ankle. Methods: The study was reviewed and approved by an institutional review board of hospital. Retrospective analysised 10 healthy volunteers and 26 ankle injury cases underwent surgery since January 2013 to September 2016, the MR imaging findings of patients were compared with volunteers' and operative documents, to analysis the MRI feature of the ligament injuries of the ankle. Results: The normal anterior talofibular ligament and posterior talofibular ligament can be manifest in 3-4 layers of MRI, and can be fully displayed in 1 layer. The normal calcaneofibular ligament can be manifest in 3 layers of MRI, but can not be fully displayed in 1 layer. 26 cases of lateral ligament injury (including 1 case of ATFL injury, 1 case of CFL injury, 3 cases of ATFL conjunction with CFL injury, 3 cases of ATFL conjunction with CFL and PTFL injury) manifested the heterogeneous signal of the T(1)-weighted image, the ligament disruption, the increased signal intensity on fat-suppression PD-weighted image , the surrounding soft tissue edema and bone marrow edema. Conclusion: MR imaging is an accurate method for evaluation of the ligament injuries of the ankle, and it is a useful tool for diagnosis and treatment.

A transcriptional cofactor YAP regulates IFNT expression via transcription factor TEAD in bovine conceptuses.

Interferon tau (IFNT) is the pregnancy recognition protein in all ruminants, and its expression is restricted to trophoblast cells. Interferon tau production increases as the conceptus elongates; however, its expression is downregulated soon after the initiation of conceptus attachment to the uterine epithelium. Our previous study identified that among 8 bovine IFNT genes, only 2 forms of IFNTs, IFNT2 and IFN-tau-c1, were expressed by the conceptuses during the periattachment period. To characterize whether Hippo signaling including a transcription cofactor yes-associated protein (YAP) was involved in the IFNT regulation, we examined the expression and effects of YAP and/or TEAD in human choriocarcinoma JEG3 and bovine trophoblast CT-1 cells, and in bovine conceptuses obtained from day 17, 20 or 22 pregnant animals (pregnant day 19.5 = day of conceptus attachment to the endometrium). YAP was expressed in bovine conceptuses and transfection of YAP or TEAD4, a transcription factor partner of YAP, expression plasmid increased the luciferase activity of IFNT2 and IFN-tau-c1 reporter plasmids in JEG3 cells. In the presence of YAP expression plasmid, TEAD2 or TEAD4 expression plasmid further upregulated transcriptional activity of IFNT2 or IFN-tau-c1 constructs, which were substantially reduced in the absence of the TEAD-binding site on IFNT2 or IFN-tau-c1 promoter region in JEG3 cells. In CT-1 cells, treatment with TEAD2, TEAD4, or YAP small-interfering RNA downregulated endogenous IFNT expression. It should be noted that TEAD2 and TEAD4 were predominantly localized in the nuclei of trophectoderm of Day 17 conceptuses, but nuclear localization appeared to be lower in those cells of conceptuses on days 20 and 22 of pregnancy. Moreover, the binding of TEAD4 to the TEAD-binding site of the IFN-tau-c1 promoter region in day 17 conceptuses was less in day 20 and 22 conceptuses. Furthermore, the level of YAP phosphorylation increased in day 20 and 22 conceptuses. These results indicated that although YAP/TEAD had the ability to up-regulate IFNT gene transcription on day 17, IFNT2 or IFN-tau-c1 was down-regulated following changes in the localization of TEAD2 and TEAD4 from the nucleus to the cytoplasm and increases in phosphorylation and degradation of YAP. These data suggest that TEAD relocation and/or YAP degradation following its phosphorylation down-regulates IFNT gene transcription after conceptus attachment to the uterine endometrium.

MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation.

Deregulation of microRNAs in human malignancies has been well documented, among which microRNA-186 (miR-186) has an antiproliferative role in some carcinomas. Here we demonstrate that low expression of miR-186 facilitates aerobic glycolysis in gastric cancer. MiR-186 suppresses cell proliferation induced by hypoxia inducible factor 1 alpha (HIF-1α) in gastric cancer cell lines MKN45 and SGC7901. Cellular glycolysis, including cellular glucose uptake, lactate, ATP/ADP and NAD+/NADH ratios, are also inhibited by miR-186. The negative regulation of miR-186 on HIF-1α effects its downstream targets, including programmed death ligand 1 and two glycolytic key enzymes, hexokinase 2 and platelet-type phosphofructokinase. The antioncogenic effects of miR-186 are proved by in vivo xenograft tumor experiment. The results demonstrate that the miR-186/HIF-1α axis has an antioncogenic role in gastric cancer.

Roles of oxidative DNA damage of bone marrow hematopoietic cells in steroid-induced avascular necrosis of femoral head.

An animal model of steroid-induced avascular necrosis of femoral head (SANFH) was established to investigate the role of oxidative DNA damage of bone marrow hematopoietic cells in SANFH. Forty-five-month-old Japanese white rabbits (male or female, 2.5 ± 0.5 kg) were randomly divided into groups A (methylprednisolone + Escherichia coli endotoxin), B (methylprednisolone alone), C (E. coli endotoxin alone), and D (blank control). The animals were sacrificed two and four weeks after administration of the last dose (N = 5 each group and each time). Left and right femoral heads were fixed and decalcified. Empty lacunae were counted by hematoxylin and eosin staining and oxidative DNA damage of bone marrow hematopoietic cells was detected by immunohistochemistry. At week 2, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference between groups B, C, and D. At week 4, the rate of oxidative DNA damage in bone marrow hematopoietic cells was significantly higher in group A than in groups B, C, and D (P < 0.01), while there was no significant difference among groups B, C, and D. Thus, oxidative DNA damage of bone marrow hematopoietic cells appears to play an important role in SANFH.