Pregnancy ; Female ; Humans ; Placenta ; Nuclear Transfer Techniques ; Embryo, Mammalian ; Cell Nucleus

Based on the theory of surgical membrane anatomy and the abnormality of membranous structure under the condition of intra-abdominal infection, the authors creatively propose the concept of partition of intra-abdominal infection, and briefly explain the definition, content and significance, which has caused widespread resonance in the academic community. Combining the clinical practices and relevant literatures, several key issues related with diagnosis and therapy in the view of D region are discussed in depth, aiming at theoretical basis for scientific planning of treatment strategies and optimal system of diagnosis and treatment of intra-abdominal infection.

Intracerebral hemorrhage is the bleeding caused by spontaneous non-traumatic rupture of blood vessels in brain parenchyma. It has high disability rate and mortality. A series of injuries after intracerebral hemorrhage will lead to neuronal apoptosis. If apoptotic neurons are not cleared in time, intracellular toxic substances will be released, thereby further aggravating the inflammatory reaction. Therefore, the timely clearance of apoptotic cells is of great significance to the brain homeostasis after intracerebral hemorrhage. At the same time, a large number of phagocytic "eat me" signal phosphatidylserine (PS) will appear on the surface of apoptotic neurons. Microglia, as resident macrophages in the brain, have a variety of PS receptors on their surface, which promote the phagocytosis of apoptotic neurons by microglia and reduce the occurrence of local inflammatory responses.

Background Parabens, a widely used class of preservatives, are suspected to be potential obesogens as emerging endocrine disrupting chemicals with reproductive and developmental toxicity. Objective To analyze five urinary parabens (PBs) and estimate the associations of exposure to PBs with adiposity measures in 10-year-old school-age children. Methods A total of 471 school-age children aged 10 years from the Sheyang Mini Birth Cohort were enrolled in this study. A questionnaire survey was conducted to collect socio-demographic information, physical activity, and dietary intake. Weight, height, and waist circumference of children were measured, and age- and sex-adjusted body mass index (BMI-Z score) was calculated. Spot urine samples were collected during the follow-up visits. Urinary concentrations of five PBs including methyl-paraben (MeP), ethyl-paraben (EtP), propyl-paraben (PrP), butyl-paraben (BuP), and benzyl-paraben (BzP) were detected by gas chromatography-tandem mass spectrometry (GC-MS/MS). Generalized linear models (GLMs) and Bayesian kernel machine regression (BKMR) models were applied to estimate associations of individual/overall urinary PBs concentrations with BMI Z-score and waist circumference. Results The positive rates of selected five urinary PBs were in the range from 78.98% to 98.94%. The urinary PBs concentrations (geometric mean) were in the range of 0.31-5.43 μg·L⁻¹. The children's BMI Z-score and waist circumference (mean ± standard deviation) were (0.56±1.40) and (67.62±10.07) cm respectively. The GLMs results showed that the urinary BzP concentration was negatively associated with waist circumference (b=−0.08, 95%CI: −0.14, −0.02; P=0.01). In sex-stratified analysis, the urinary concentration of BzP was negatively associated with BMI-Z score (b=−0.59, 95%CI: −0.88, −0.30; P<0.001) and waist circumference (b=−0.80, 95%CI: −1.23, −0.37; P<0.001) in boys, but not in girls. The BKMR results also found significant negative correlations of urinary BzP concentrations with BMI-Z score and waist circumference, which were consistent with the GLM results. Conclusion The selected 10-year-old children are extensively exposed to PBs in the study area. Furthermore, childhood PBs exposure may have potential impacts on childhood adiposity measures with sex-specific effects.

The disability and mortality rate of patients with intracerebral hemorrhage are very high. At present, there is no effective treatment to improve the outcome of patients with intracerebral hemorrhage. Mechanical compression of hematoma and release of toxic products are the main causes of primary and secondary brain injury in patients with intracerebral hemorrhage, while safe and effective acceleration of hematoma regression is the key strategy to improve the neurological deficit in patients with intracerebral hemorrhage. Microglia/macrophages are the main phagocytic system that mediates hematoma clearance and are mainly polarized into M1 and M2 phenotypes. Cell surface receptors and possible signal transduction pathways play an important role in regulating the endogenous hematoma regression mediated by microglia/macrophages, and may become a new target for clinical treatment of intracerebral hemorrhage and improvement of the outcomes of patients in the future.

The proteolysis targeting chimeras (PROTACs) technology has been rapidly developed since its birth in 2001, attracting rapidly growing attention of scientific institutes and pharmaceutical companies. At present, a variety of small molecule PROTACs have entered the clinical trial. However, as small molecule PROTACs flourish, non-small molecule PROTACs (NSM-PROTACs) such as peptide PROTACs, nucleic acid PROTACs and antibody PROTACs have also advanced considerably over recent years, exhibiting the unique characters beyond the small molecule PROTACs. Here, we briefly introduce the types of NSM-PROTACs, describe the advantages of NSM-PROTACs, and summarize the development of NSM-PROTACs so far in detail. We hope this article could not only provide useful insights into NSM-PROTACs, but also expand the research interest of NSM-PROTACs.

ObjectiveTo investigate the regulatory effect of Shoutaiwan on oxidative stress and pyroptosis in lipopolysaccharide （LPS）-induced human extravillous trophoblast （HTR-8/SVneo） cells and provide a new direction for deciphering the mechanism of action of Shoutaiwan. MethodLPS （100 μg∙L^-1） was used to induce the injury of HTR-8/SVneo cells （modeling）. Five groups were designed in this study， including a blank group， a model group， a Shoutaiwan （10% Shoutaiwan-containing serum） group， an antioxidant （1 mmol·L^-1 NAC） group， and NOD like receptor thermoprotein domain 3 （NLRP3） inhibitor （50 μmol·L^-1 MCC950） group. Cell viability was detected by cell counting kit-8 （CCK-8） kit. Hochest 33342/PI double fluorescence staining and flow cytometry were employed to observe cell death. The levels of interleukin-18 （IL-18）， interleukin-1β （IL-1β）， malondialdehyde （MDA）， and superoxide dismutase （SOD） in cell supernatant was determined by enzyme-linked immunosorbent assay （ELISA）. DCFH-DA probe was used to measure the level of intracellular reactive oxygen species （ROS）. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， gastermin D （GSDMD）， and IL-1β in cells， and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） to measure the mRNA levels of NLRP3 and Caspase-1 in cells. ResultCompared with the blank group， the modeling decreased the cell viability （P<0.01）， elevated the levels of IL-1β， IL-18， ROS， and MDA， and weakened the activity of SOD （P<0.01）. Furthermore， it up-regulated the protein levels of NLRP3， Caspase-1， GSDMD， and IL-1β and the mRNA levels of NLRP3 and Caspase-1 （P<0.01）. Compared with the model group， Shoutaiwan， NAC， and MCC950 increased the cell viability （P<0.01）. Further， Shoutaiwan and NAC lowered the levels of MDA and ROS and increased the activity of SOD （P<0.01）. Shoutaiwan and MCC950 reduced the IL-1β and IL-18 in cell supernatant （P<0.01）， and down-regulated the protein levels of NLRP3， Caspase-1， GSDMD， and IL-1β and the mRNA levels of NLRP3， Caspase-1， and IL-1β （P<0.05，P<0.01）. ConclusionShoutaiwan can regulate oxidative stress and pyroptosis to attenuate the LPS-induced damage of HTR-8/SVneo cells， which may be the mechanism of Shoutaiwan in preventing recurrent spontaneous abortion.

Purpose: Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver primary tumors but its treatments are limited. Bioinformatics showed that the expression level of long non-coding RNA cancer-associated susceptibility 15 gene (CASC15) is correlated with ICC progression, but its functional mechanism remains unclear. Materials and Methods: Tissues from ICC patients, tumor and adjacent tissue, were used for detection of the expression of CASC15. Clinical data were also collected for clinicopathologic and survival analysis. Short interfering RNA and lentiviral short hairpin RNA were used to knock down CASC15 and PRDX2 expression in ICC cell lines, for the analysis of changes of cell function and xenografts. RNA-pulldown and RNA immunoprecipitation assays were used to detect RNA-binding protein, PRDX2. Male nude mice were used for ICC xenografts, and livers were collected after 4 weeks for immunohistochemistry. Results: CASC15 is highly expressed in ICC tissues and is related to higher TNM stage. Knockdown of CASC15 in ICC cells reduced cell proliferation, migration, invasiveness and increased apoptosis, and G1/S block. PRDX2 bound to CASC15. Knockdown of CASC15 decreased PRDX2 expression which was rescued by the inhibition of proteasome formation. Downregulation of PRDX2 resulted in G1/S block, reduced ICC cell invasion. Downregulation of CASC15 inhibited phosphoinositide 3-kinase (PI3K)/AKT/c-Myc pathway through downregulating of PRDX2 and overexpressed PRDX2 rescued the block. CASC15 knockout in ICC xenografts suppressed tumor development in vivo, decreased the expression of PRDX2 and Ki67 and inhibited PI3K/AKT pathway. Conclusion CASC15 promotes ICC possibly by targeting PRDX2 via the PI3K/AKT pathway, indicating poor prognosis and high degree of malignancy of ICC.

Objective:To investigate the diagnosis and treatment of hepatic artery thrombosis (HAT) after adult orthotopic liver transplantation.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 411 patients who underwent adult orthotopic liver transplantation in the First Affiliated Hospital of Xi ′an Jiaotong University from December 2011 to July 2018 were collected. There were 328 males and 83 females, aged from 21 to 66 years, with a median age of 46 years. Observation indicators: (1) incidence of HAT and its clinical characteristics; (2) diagnosis of HAT; (3) treatment of HAT; (4) follow-up. Follow-up using outpatient service, telephone interview or WeChat group communication was conducted to detect the incidence of biliary stricture and survival of patients up to August 2018. Measurement data with normal distribution were represented as Mean± SD, measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Survival rate was estimated using the Kaplan-Meier method. Results:(1) Incidence of HAT and its clinical characteristics: 11 of 411 patients had HAT after orthotopic liver transplantation with the incidence of 2.68%(11/411), including 10 males and 1 female, aged 44 years(range, 22-63 years). The time to occurrence of postoperative HAT was 4 days(range, 1-15 days). The etiologies of 11 patients included 6 cases of hepatitis B virus-related cirrhosis, 1 case of hapatitis related cirrhosis, 1 case of hepato-cellular carcinoma, 1 case of liver cirrhosis, 1 case of alcoholic hepatitis related cirrhosis, 1 case of wilson disease. All the 11 patients were ABO compatible. The cold ischemic time and warm ischemic time of donor liver were (316±89)minutes and (13±4)minutes, respectively. Type Ⅰ arterial anasto-mosis was conducted in 11 patients. The clinical manifestations included asymptomatic type in 10 patients and sepsis type in 1 patient. (2) Diagnosis of HAT: all the 11 patients were confirmed with HAT by endovascular angiography, including 7 cases showed no arterial flow under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. Two patients showed increased hepatic artery resistance index under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated 1 case of HAT and 1 case of anastomotic stenosis. One patient showed slow velocity of hepatic artery blood flow and low resistance index under color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. One patient showed slight blood flow signals under Color Doppler ultrasound, and contrast-enhanced ultrasound indicated HAT. (3) Treatment of HAT: 11 patients received endovascular therapy. Six patients had HAT completely disappeared after thrombolytic therapy, 5 patients with residual thrombosis continued thrombolytic therapy with microcatheter urokinase. Six patients with complications were improved after symptomatic treatment. HAT completely disappeared after (6.7±2.6)days of treatment and the clinical success rate was 11/11. (4) Follow-up: 11 patients were followed up for 19-1 722 days, with a median follow-up time of 46 days. During the follow-up, 4 patients had biliary stricture and underwent stent implantation. Nine patients survived with 1-, 3-, 5-year overall survival rates of 75%, 75%, 75%, and 2 patients died.Conclusions:The incidence of HAT after adult orthotopic liver transplantation is low and clinical manifestations are atypical. Contrast enhanced ultrasound can improve diagnosis of suspected thrombosis. Endovascular therapy is safe and effective, which can significantly improve the blood flow of hepatic artery.

Enteral nutrition is an indispensable part of the treatment for critically ill patients. Various authoritative guidelines point out that early enteral nutrition is the key to improve the prognosis of disease. The key to improve and promote standardized enteral nutrition for criti-cally ill patients is the application of guidelines in the clinical practice. Based on clinical practice and theoretical basis, the authors propose a new insight into enteral nutrition and a new nutritional strategy of "individual treatment, circular evaluation, channel basis, quality-quatity balance, step-up achievement" for critically ill patients on basis of a 5W1H mindset.