Heralded Three-Photon Entanglement from a Single-Photon Source on a Photonic Chip.

In the quest to build general-purpose photonic quantum computers, fusion-based quantum computation has risen to prominence as a promising strategy. This model allows a ballistic construction of large cluster states which are universal for quantum computation, in a scalable and loss-tolerant way without feed forward, by fusing many small n-photon entangled resource states. However, a key obstacle to this architecture lies in efficiently generating the required essential resource states on photonic chips. One such critical seed state that has not yet been achieved is the heralded three-photon Greenberger-Horne-Zeilinger (3-GHZ) state. Here, we address this elementary resource gap, by reporting the first experimental realization of a heralded 3-GHZ state. Our implementation employs a low-loss and fully programmable photonic chip that manipulates six indistinguishable single photons of wavelengths in the telecommunication regime. Conditional on the heralding detection, we obtain the desired 3-GHZ state with a fidelity 0.573±0.024. Our Letter marks an important step for the future fault-tolerant photonic quantum computing, leading to the acceleration of building a large-scale optical quantum computer.

[Study on the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogelin post-traumatic osteoarthritis].

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats (n=70), and the sham surgery group (n=70) was set as control. The changes in inflammatory indicators such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n=70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n=70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2,n=18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro (n=18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group(P=0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P=0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 ß, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P<0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P=0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P<0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

[Prognostic factors for non-small cell lung cancer patients with central nervous system metastasis with positive driver genes].

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients' prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients' prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ2=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

[Antimicrobial resistance and plasmid-mediated colistin resistance mechanism of diarrheagenic Escherichia coli recovered from foods in parts of China in 2020].

Objective: To investigate the antimicrobial resistance of food-borne diarrheagenic Escherichia coli (DEC) and the prevalence of mcr genes that mediates mobile colistin resistance in parts of China, 2020. Methods: For 91 DEC isolates recovered from food sources collected from Fujian province, Hebei province, Inner Mongolia Autonomous Region and Shanghai city in 2020, Vitek2 Compact biochemical identification and antimicrobial susceptibility testing platform was used for the detection of antimicrobial susceptibility testing (AST) against to 18 kinds of antimicrobial compounds belonging to 9 categories, and multi-polymerase chain reaction (mPCR) was used to detect the mcr-1-mcr-9 genes, then a further AST, whole genome sequencing (WGS) and bioinformatics analysis were platformed for these DEC isolates which were PCR positive for mcr genes. Results: Seventy in 91 isolates showed different antimicrobial resistance levels to the drugs tested with a resistance rate of 76.92%. The isolates showed the highest antimicrobial resistance rates to ampicillin (69.23%, 63/91) and trimethoprim-sulfamethoxazole (59.34%, 54/91), respectively. The multiple drug-resistant rate was 47.25% (43/91). Two mcr-1 gene and ESBL (extended-spectrum beta-lactamase) positive EAEC (enteroaggregative Escherichia coli) strains were detected. One of them was identified as serotype of O11:H6, which showed a resistance profile to 25 tested drugs referring to 10 classes, and 38 drug resistance genes were predicted by genome analysis. The other one was O16:H48 serotype, which was resistant to 21 tested drugs belonging to 7 classes and carried a new variant of mcr-1 gene (mcr-1.35). Conclusion: An overall high-level antimicrobial resistance was found among foodborne DEC isolates recovered from parts of China in 2020, and so was the MDR (multi-drug resistance) condition. MDR strains carrying multiple resistance genes such as mcr-1 gene were detected, and a new variant of mcr-1 gene was also found. It is necessary to continue with a dynamic monitoring on DEC contamination and an ongoing research into antimicrobial resistance mechanisms.

[Notch1 inhibits the mechanistic role of STING signaling to regulate hepatocyte lipophagy in nonalcoholic steatohepatitis].

Objective: To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy. Methods: A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1(FL/FL) mice were randomly divided into two groups: the Notch1(FL/FL) + normal diet (NCD) and the Notch1(FL/FL) + HFD group. Further, 12 Notch1(M-KO) mice were randomly divided into two groups: Notch1(M-KO) + NCD, and Notch1(M-KO) + HFD group.Serum alanine aminotransferase (sALT), total cholesterol (TC) and triglyceride (TG) were collected from mice serum samples. Liver tissue samples were collected for H&E staining, immunofluorescence (IF), Western blot and qRT-PCR. Tumor necrosis factor (TNF)-α was detected in the supernatant by enzyme-linked immunosorbent assay (ELISA). The comparison of inter group data was conducted using a t-test. Results: The mouse NASH model, mouse BMMs co-culture system, and primary hepatocytes were successfully constructed. Compared with the Notch1(FL/FL) + HFD group, the Notch1(M-KO) + HFD group showed a significant increase in serum ALT [(250.02 ± 58.21) U/L vs (370.70 ± 54.57) U/L, t = 3.705, P = 0.004], TG [(29.90 ± 3.54) mg/g vs (43.83 ± 8.56) mg/g, t = 3.685, P = 0.004], and TC [(33.70 ± 8.43) mg/g vs (90.53 ± 12.53) mg/g, t = 9.917, P < 0.001]. HE staining of liver tissue showed remarkable balloon-like alterations in liver cells, while IF staining demonstrated increased macrophage infiltration (t = 7.346, P < 0.001). Compared with the hepatocyte group co-cultured with Notch1(FL/FL) BMMs, the BODIPY probe showed a significant increase in lipid droplet (LDs) deposition in liver cells in the Notch1(M-KO) group (t = 3.835, P < 0.001). The co-localization of lysosomal associated membrane protein 1 (LAMP1), LDs (t = 7.103, P < 0.001), microtubule-associated protein light chain 3 (LC3) -II/LC3-I (t = 5.0, P = 0.007), and autophagy associated gene 12 (Atg12) (t = 28.36, P < 0.001) had decreased expression, while P-62 had increased expression (t = 3.253, P = 0.03), indicating a decrease in autophagic flow. Additionally, LC3 and LDs colocalization decreased (t = 5.24, P = 0.0003), indicating reduced lipophagy. Compared with the Notch1(FL/FL) group, the Notch1(M-KO) BMMS mouse group showed an increase in the expression of p-STING (t = 5.318, P = 0.006), p-TANK1 binding kinase 1 (TKB1) (t = 6.467, P = 0.002), p-interferon regulatory factor 3 (IRF3) (t = 14.61, P < 0.001), and p-P65 (t = 12.7, P = 0.002) protein, accompanied by mRNA expression of the inflammatory mediators interferon (IFN)-ß (t = 7.978, P < 0.001), TNFα (t = 8.496, P = 0.001), interleukin-1 ß (IL-1 ß) (t = 4.7, P < 0.001), and CXCL-10 (t = 4.428, P = 0.001). The STING gene was knocked out in the BMMs Notch1(M-KO) mice using CRISPR/Cas9. Compared with the CRISPR-Control group, the expression of P-TKB1 (t = 2.909, P = 0.044), p-IRF3 (t = 10.96, P < 0.001), p-IRF3 (t = 10.96, P < 0.001), and p-P65 (t = 7.091, P = 0.002) proteins was lower in the STING-KO BMMs group. The release of TNF-α in the supernatant was decreased (732.3 ± 129.35 pg/ml vs. 398.17 ± 47.15 pg/ml, t = 4.204, P = 0.014). However, in hepatocytes co-cultured with STING-KO BMMs, LC3-II/LC3-I (t = 7.546, P = 0.001) increased, p-62 (t = 10.96, P < 0.001) expression decreased, autophagic flow increased, and the colocalization of LC3 and LDs increased, lipophagy increased, and LDs deposition decreased. Conclusion: Myeloid-specific Notch1 knockout can activate macrophages STING signaling, increase the expression of inflammatory mediator genes, inhibit the occurrence of autophagy flow and lipophagy in hepatocyte cells, and aggravate LDs deposition and NASH progression.

[Value of hypoxic burden in evaluating the impairments of organ systems in obstructive sleep apnea].

Obstructive sleep apnea (OSA) is a common sleep-disordered-breathing with decreased or even suspended ventilation due to upper airway obstruction, which is characterized by intermittent hypoxia and sleep fragmentation. OSA can damage a variety of organ systems, especially the cardiovascular system, seriously affecting the quality of life of patients. Therefore, more attention is paid to the precise assessment of the impairments of the organ systems caused by OSA and the evaluation of indicators, in order to carry out preventive measures as soon as possible. However, due to the limitations of traditional indicators such as apnea-hypopnea index (AHI) in assessing the severity of disease, it is necessary to explore other alternative indicators to obtain multi-dimensional characteristics of OSA. A promising parameter, hypoxic burden (HB) can better quantify the severity of OSA and capture the disease load of OSA. This review mainly focused on the basic concept, main features, calculating method of HB and its clinical significance in predicting the adverse consequences of OSA, aiming at a better management of patients with OSA.

[Study on the etiological characteristics and prevention and control of adult community-acquired pneumonia in hospitalized patients in a hospital in Beijing from 2015 to 2019].

Objective: To explore the distribution characteristics of pathogens in adult patients with community-acquired pneumonia (CAP) and to provide basis for the diagnosis, treatment, prevention of CAP. Methods: 1 446 inpatients with CAP were prospectively enrolled in a third-class hospital in Beijing in recent 5 years (from January 2015 to December 2019). Respiratory tract samples were collected for smear, culture, nucleic acid, antigen and antibody detection to identify the pathogen of CAP. Mann-Whitney U test was used for continuous variables and χ2 test or Fisher's exact test was used for categorical data for statistical analysis. Results: Among the 1 446 patients, 822 (56.85%) patients were infected with a single pathogen, 231 (15.98%) patients were infected with multiple pathogens, and 393 (27.18%) patients were not clear about the pathogen. Influenza virus is the first pathogen of CAP (20.95%, 303/1 446), mainly H1N1 (8.51%, 123/1 446), followed by mycoplasma pneumoniae (7.19%, 104/1 446), Mycobacterium tuberculosis (5.33%, 77/1 446) and Streptococcus pneumoniae (5.05%, 73/1 446). The outbreak of H1N1 occurred from December 2018 to February 2019, and the epidemic of mycoplasma pneumoniae pneumonia was monitored from August to November 2019. Patients under 65 years old had high detection rates of Mycoplasma pneumoniae (14.41% vs. 2.41%, χ²=74.712,P<0.001), Streptococcus pneumoniae (8.16% vs. 2.99%, χ²=18.156, P<0.001), rhinovirus (6.08% vs. 3.56%, χ²=5.025, P<0.025), Chlamydia pneumoniae (5.90% vs. 1.15%, χ²=26.542, P<0.001) and adenovirus (3.13% vs. 0.92%, χ²=9.547, P=0.002). The severe disease rate of CAP was 14.66% (212/1 446), and the average mortality rate was 3.66% (53/1 446). The severe illness rate and mortality rate of bacterial-viral co-infection were 28.97% (31/107) and 19.63% (21/107), respectively. Conclusions: Influenza virus is the primary pathogen of adult CAP. Outbreaks of Mycoplasma pneumoniae and H1N1 were detected in 2018 and 2019, respectively. The remission rate and mortality rate of virus-bacteria co-infection were significantly higher than those of single pathogen infection. Accurate etiological basis not only plays a role in clinical diagnosis and treatment, but also provides important data support for prevention and early warning.

[Clinical characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease].

Objective: To study the clinical and etiological characteristics of viral pneumonia in patients with chronic obstructive pulmonary disease(VP-COPD), and to identify the risk factors associated with poor prognosis. Methods: From August 1, 2017 to August 1, 2019, totally 235 patients in a general hospital in Beijing were prospectively enrolled in this research, and all patients were diagnosed with viral pneumonia by imaging and etiology. The patients were divided into VP-COPD group(n=60) and VP-nCOPD(viral pneumonia in non-COPD patients) group(n=175). Pathogen detection and clinical characteristics were compared between the two groups.Finally, the binomial logistic regression was used to explore the risk factors associated with severe VP-COPD. Results: Compared with the VP-nCOPD group, the VP-COPD group was older(76.5 vs 66.0 years, P=0.001), and the CURB-65 score(2 vs 1, P= 0.001) and the PSI score(111 vs 85, P<0.001) were higher at admission. Pseudomonas aeruginosa(χ²= 10.308, P= 0.001) and Staphylococcus aureus(χ²= 5.953, P=0.028) were the most common co-infection bacteria. In the VP-COPD group type Ⅱ respiratory failure was more common(23.3% vs 6.8%, P<0.001), the number of severely ill patients was larger(48.3% vs 30.3%, P=0.011), the length of hospital stay was longer(13 vs 8, P<0.001), and the mortality rate during hospitalization was higher(18.3% vs 7.4%, P=0.016) in the VP-nCOPD group. Multivariate analysis showed that the level of blood glucose(OR: 1.73, 95%CI: 1.22-2.44, P= 0.002) and pleural effusion(OR: 133.12, 95%CI: 7.57-2 340.36, P=0.001) were risk factors for severe VP-COPD patients. Conclusion: Viral pneumonia in patients with COPD tended to develop into severe cases and had a poor prognosis.

[The study on the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis].

Objective: To explore the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis (CWP) , the relationship of extracellular histones in plasma with pulmonary fibrosis caused by coal mine dust was analyzed, and the stimulating effect of extracellular histones on fibroblast proliferation was studied. Methods: In May 2019, a total of 220 coal mine dust exposure workers (including coal miners and CWP patients) who visited the occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61 coal miners were in category 0 SOP, 65 coal miners were in category 1 SOP, 56 coal miners were in category 2 SOP and 38 coal miners were in category 3 SOP. The plasma levels of extracellular histone H4 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients' plasma and calf thymus histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro. Results: Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years, coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of histone H4 in the coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) 、(9.84±4.17) 、(14.35±5.52) and (17.83±7.69) µg/ml, respectively. There were significant differences among the four groups (P<0.01) . The plasma level of histone H4 was positively correlated with the plasma level of PDGF in the coal miners (r=0.769, P<0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased (P<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased (P<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased (P<0.05) . Conclusion: Extracellular histones in plasma are associated with pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular histones can be important biomarkers for pulmonary fibrosis caused by coal mine dust.

Effects of Sca-1(+) bone marrow mesenchymal stem cells on lung ischemia-reperfusion injury.

This study aimed to explore the effect of Sca-1+ bone marrow stromal stem cells (BMSCs) on lung ischemia reperfusion injury in mice. Five healthy Sprague-Dawley rats were selected to isolate and purify their Sca-1+ BMSCs using a Sca-1+ magnetic sorting kit in conjunction with whole bone marrow culture. In addition, 21 male C57BL/6J mice were divided into 3 groups (7 mice in each group), namely sham group (group A), I/R group (group B) and BMSCs group (group C). A pulmonary ischemia reperfusion injury model was established by ligating the left pulmonary portal vessel for 60 min and reperfusion for 240 min, after which the right pulmonary portal vessel was blocked to measure arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Subsequently, the mice were sacrificed to determine their superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and myeloperoxidase (MPO) activity in the lung tissue. The histological changes were observed by light microscopy, while an enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in plasma expressions of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the mice. In addition, plasma expressions of TNF-α and B-cell lymphoma-2 (bcl-2) in the mice were detected by immunohistochemistry, while the apoptosis of transplanted lung cells was detected by a TdT-mediated dUTP Nick-End Labeling (TUNEL) method. Compared with group A, group B showed a decreased level of PaO2 and SOD activity but an increased level of MDA content and MPO activity (P less than 0.01), indicating that group B had significant ischemia reperfusion injury compared to group A. In conclusion, BMSCs significantly reduced lung ischemia-reperfusion injury and improved lung function through their anti-oxidation, anti-inflammatory and anti-apoptosis properties.

[Effect of umbilical cord mesenchymal stem cells on biological characteristics of esophageal cancer EC1 cells].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (MSCs) on the proliferation, apoptosis, migration, invasion and stemness of esophageal cancer EC1 cells. Methods: Human umbilical cord mesenchymal stem cells were isolated and cultured in vitro, and cell phenotype was identified by flow cytometry. MSCs or their conditioned medium were co-cultured with esophageal cancer EC1 cells. The effects on the proliferation, apoptosis, migration, invasion and stemness of EC1 cells were examined by cell counting kit-8 (CCK-8), flow cytometry, Transwell, quantitative real-time polymerase chain reaction (RT-qPCR) and spheroid formation assays. Results: MSCs inhibited the proliferation of EC1 cells in a concentration dependent manner. When the ratio of MSCs to EC1 cells was 0∶1, 1∶1, 2∶1, 5∶1, the apoptotic rates of EC1 cells were (4.07±0.34)%, (8.90±0.36)%, (10.80±0.50)% and (15.23±1.06)%, respectively, suggesting that MSCs promoted the apoptosis of EC1 cells in a concentration dependent manner (all P<0.05). The expression levels of OCT2, SOX2, KLF4, CXCR4 and CXCR7 in EC1 cells cultured in 80% conditioned medium were 0.53±0.03, 0.49±0.02, 0.73±0.09, 0.57±0.05 and 0.24±0.02, respectively, which were lower than those in the regular medium group (all P<0.05). The numbers of migrated cells in regular medium as well as 10%, 40%, and 80% conditioned medium were 287.3±21.6, 280.7±15.5, 264.3±16.8, and 257.7±8.0, respectively. Meanwhile, the numbers of invasive cells were 194.3±16.6, 213.7±24.3, 221.0±16.0, (252.0±20.4), respectively. There was no significant difference between the groups (all P>0.05). Conclusion: Human umbilical cord mesenchymal stem cells can inhibit the proliferation, promote apoptosis and reduce the stemness, and have no significant effect on the migration and invasion of EC1 cells.

[Activation of lung endothelial cells by extracellular histone in mice with acute respiratory distress syndrome].

Objective: To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) . Methods: The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model. Results: The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells. Conclusion: Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.

Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC.

The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

[Analysis of neoadjuvant docetaxel, carboplatin and trastuzumab (TCH) in HER-2-positive breast cancer].

Objective: To analyze docetaxel (T) and carboplatin (C) combined with trastuzumab (H) -TCH regimen as neoadjuvant systemic therapy in early breast cancer patients with human epidermal growth factor receptor 2 (HER-2) positive. Methods: From January 2008 to December 2014, the data of patients diagnosed as early breast cancer in Breast Disease Center of Peking University First Hospital were retrospective reviewed. The data of patients with HER-2 positive conducted TCH neoadjuvant therapy and surgery, and with the complete clinicopathological information were analyzed. Results: A total of 77 cases were enrolled in this study. We defined G2+ G3+ G4+ G5 as responsive group according to Miller-Payne grading system, the responsive rate was 84.4% (65/77). The rate of complete pathological remission (pCR) was 39.0% (30/77). The 5-year disease free survival (DFS) was 87.3%, and 5-year overall survival (OS) was 93.6%. There was a significant difference between DFS and OS in the responsive group and non-responsive group (DFS: χ2=6.762, P=0.009; OS: χ2=5.062, P=0.024). Conclusion: TCH is an effective neoadjuvant therapy for patients with HER-2 positive breast cancer, and the toxic and side effects were under control.

[Clinical characteristics and treatment of congenital fibrovascular pupillary membranes].

Objective: To investigate the clinical characteristics, surgical approaches and postoperative effects associated with congenital fibrovascular pupillary membranes. Methods: A retrospective study design was used. Thirteen children (13 eyes) with congenital fibrovascular pupillary membranes, treated in Beijing Children's Hospital from January 2014 to December 2017 were included. The morphology of the membrane and the anterior chamber was evaluated using a digital wide-area fundus imaging system. The ophthalmic signs, examination results, operation methods, intraocular pressure and ocular position were analyzed. Results: There were 13 children (13 eyes) were enrolled, including 9 males and 4 females. The age at surgery ranged from 2.0 months to 34.5 months, with an median of 5.1 months. According to the degree of obstruction of the pupil and the intraocular pressure, the eyes were divided into three groups. In the 5 eyes of group A, the pupil membrane did not completely cover the pupil, and the depth of the anterior chamber was normal. Among them, 4 eyes had normal intraocular pressure (9-12 mmHg) (1 mmHg=0.133kPa), and 1 eye had elevated intraocular pressure (18 mmHg). In the 5 eyes of group B, the pupillary membrane completely covered the pupil into a pinhole, the anterior chamber was normal or slightly shallow, and the intraocular pressure was normal (6-16 mmHg). In the 3 eyes of group C, the pupillary membrane completely covered the pupil, the anterior chamber was shallow or disappeared, and the intraocular pressure was high (24-45 mmHg). Membranectomy and pupilloplasty were performed in group A, and trabeculectomy was combined when there was glaucoma; postoperative intraocular pressure was normal (4-10 mmHg). Membranectomy, pupilloplasty and iridectomy were performed in group B; postoperative intraocular pressure was normal (7-13 mmHg). Membranectomy, pupilloplasty, iridectomy and goniosychialysis were performed in group C; after surgery, intraocular pressure was normal in 2 eyes (10 mmHg and 13 mmHg) and 25 mmHg in 1 eye. All eyes were orthophoric before and after operation in group A. In group B, 1 eye was esotropic, 2 eyes were exotropic (worse after surgery in 1 eye), and 2 eyes were orthophoric before surgery. In group C, one eye was esotropic, one eye was exotropic, and one eye was orthophoric before surgery, and all eyes were exotropic after operation. Conclusions: Congenital fibrovascular pupillary membranes are unilaterally a continuation of the iris covering the pupil at different degrees, with or without glaucoma. Surgical treatment should be performed promptly when there is obscuring of the visual axis or incorporating of glaucoma. The main surgical procedures are membranectomy and pupilloplasty and iridectomy. Postoperative intraocular pressure can be well controlled, and strabismus has no improvement. (Chin J Ophthalmol, 2018, 54:849-854).

[The comparison of heparan sulfate and its fragments on the protection against extracellular histones during the pathogenesis of acute respiratory distress syndrome].

Objective: In order to explore the role of heparan sulfate (HS) during the pathogenesis of acute respiratory distress syndrome (ARDS) , the protective effect of HS and its fragments against extracellular histones was compared. Methods: Calf thymus histones (CTH) were injected via femoral vein to induce ARDS in rats. HS, HS fragments or saline was intraperitoneally injected (10mg/kg, Q6h, 24h) to test the protective effect against CTH. The ratio of wet/dry lung weight, protein content in bronchoalveolar lavage fluid (BALF) , total leukocyte and neutrophil count in BALF were measured. Results: After CTH injection, the ratio of wet/dry lung weight (5.7±0.95) was much higher than the saline control group (3.1±0.15). The protein content (0.47±0.086mg/ml) , total leukocyte[ (97.4±15.6l) ×10(4)/ml] and neutrophil (18±3.4/LPF) in BALF were obviously increased compared with the saline control group. The intervention of HS evidently decreased ratio of wet/dry lung weight (4.2±0.41) , protein content[ (0.26±0.019) mg/ml], leukocyte[ (61.3±5.74) ×10(4)/ml] and neutrophil (12±1.8/LPF) in BALF. HS fragments also decreased ratio of wet/dry lung weight, protein content, leukocyte and neutrophil count in BALF though the strength was much less than HS. Conclusion: HS and its fragments could provide protection against extracellular histones during the pathogenesis of ARDS. For the protective effect full length HS was much better than HS fragments.

Transcriptome and proteome analyses reveal complex mechanisms of reproductive diapause in the two-spotted spider mite, Tetranychus urticae.

Although a variety of factors underlying diapause have been identified in arthropods and other organisms, the molecular mechanisms regulating diapause are still largely unknown. Here, to better understand this process, we examined diapause-associated genes in the two-spotted spider mite, Tetranychus urticae, by comparing the transcriptomes and proteomes of early diapausing and reproductive adult females. Amongst genes underlying diapause revealed by the transcriptomic and proteomic data sets, we described the noticeable change in Ca2+ -associated genes, including 65 Ca2+ -binding protein genes and 23 Ca2+ transporter genes, indicating that Ca2+ signalling has a substantial role in diapause regulation. Other interesting changes in diapause included up-regulation of (1) glutamate receptors that may be involved in synaptic plasticity changes, (2) genes involved in cytoskeletal reorganization including genes encoding each of the components of thick and thin filaments, tubulin and members of integrin signalling and (3) genes involved in anaerobic energy metabolism, which reflects a shift to anaerobic energy metabolism in early diapausing mites.

An integrated method of therapeutic lifestyle change for older adults with dyslipidaemia.

OBJECTIVES: To evaluate the effect of therapeutic lifestyle change with a non-pharmacological intervention method in older adults with dyslipidaemia. STUDY DESIGN: Stratified randomized trial. METHODS: Participants with dyslipidaemia (n = 214) aged ≥60 years were randomized to the conventional guide group, the educational course (EC) group, the telephone call (PC) group or the PC + EC group for 24 weeks. Total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and the knowledge, attitude and practice score for serum lipids were measured at baseline (T1), mid-intervention (week 12, T2) and post-intervention (week 24, T3). RESULTS: Except the conventional guide group (n = 62), the PC group (n = 56), the EC group (n = 49) and the PC + EC group (n = 47) showed significant intra-group differences in serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, high-density lipoprotein cholesterol and knowledge, attitude and practice score after the intervention. The improvements were most prominent and sustained over time in the PC + EC group at post-intervention. CONCLUSIONS: The PC + EC method is more efficient for improving serum lipids and enhancing health awareness than any single programme in older adults with dyslipidaemia. This overlapped therapeutic lifestyle change method may serve as a cost-effective adjunct and ensure the continuity of high-quality health services for patients with dyslipidaemia.

[Analysis of early response to the antipsychotic treatment and related factors in acute schizophrenia patients].

Objective: The objective was to assess the relationship between early response and later response to antipsychotics, and the relationship between antipsychotics and early response. Methods: Data were retrospectively analyzed from patients with schizophrenia and they were hospitalized in the Second Affiliated Hospital of Xinxiang Medical College from May, 2013 to September, 2015.The patients were divided into theearly response group (PANSS total score improvement ≥20% at week 2) and early nonresponse group.General information, the use of drug and the Positive and Negative Syndrome Scale (PANSS) on before and 2, 4, 6 weeks after treatment were compared between the two groups.The relation between early response and late response and the effect of drug selection on early response were analyzed by correlation analysis and regression analysis. Results: Relative to early nonresponders, early responders were significantly more likely to have lower PANSS scores (total scores on 2, 4, 6 weeks after treatment 66.2±11.8 vs 84.5±10.9, 55.9±13.2 vs 70.9±13.7, 48.9±13.1 vs 60.6±14.9, all P<0.05) and higher PANSS scores improvement at 2, 4, 6 weeks after treatment (total scores improvement on 2, 4, 6 weeks after treatment (37±14)% vs (9±7)%, (56±19)% vs (32±18)%, (68±20)% vs (49±21)%, all P<0.05). The correlation coefficient between PANSS total score improvement at week 2 and at week 4, 6 were 0.730 and 0.541, respectively (all P<0.05). Olanzapine had more PANSS total score improvement than aripiprazole, quetiapine and ziprasidone (2 weeks after treatment (29±19)% vs (19±16)%, (18±15)%, (17±15)%, 4 weeks after treatment (51±21)% vs (37±25)%, (39±18)%, (37±22)%, all P<0.05). The protective factor for early response was olanzapine (P<0.05). Conclusions: Early responders are associated with faster and greater improvement in symptoms, the type of antipsychotic has impacts on early response, early non-responders can benefit from adjustment of treatment.

[Characteristics of molecular typing and drug resistance of 67 Salmonella paratyphi A isolated in Zhengzhou from 2013 to 2015].

Objective: To investigate the antimicrobial resistance and pulsed field gel electrophoresis (PFGE) patterns of S.paratyphi A strains in Zhengzhou city isolated from sentinel hospitals in 2013-2015. Methods: According to Salmonella molecular typing and K-B drug susceptibility testing method published by international PulseNet bacterial infectious disease monitoring network and USA Clinical and Laboratory Standards Institute (CLSI2015), we analyzed drug sensitivity and PFGE molecular characteristics of 67 S.paratyphi A strains(11 strains in 2013, 7 strains in 2014, 49 strains in 2015) isolated from blood and stool samples in two sentinel hospitals of fever with rash syndrome surveillance system established in Zhengzhou city in 2013-2015. Results: The results showed 67 strains of S.paratyphi A had different levels of resistance to 13 kinds of antibiotics, 65 strains were multi-drug resistant strains (97.0%), 5 isolates were resistant to 2-3 kinds of antibiotics (7.5%), 41 isolates were resistant to 5-8 kinds of antibiotics (61.2%),11 isolates were resistant to 9-10 kinds of antibiotics(16.4%),8 isolates were resistant to 11-12 kinds of antibiotics(11.9%). 67 strains of S.paratyphi A were divided into 10 molecular patterns(PTYA1-PTYA10) by digestion with XbaⅠ restriction endonuclease and pulsed field gel electrophoresis, each pattern contains 1-48 strains with similarity ranged from 94.31%-100%. PTYA3 contained 48 strains, which was predominant band type; PTYA1, 9 contained 6 strains; PTYA 2, 4, 5, 6, 7, 8, 10 contained 1 strains among them. Conclusion: The status of drug resistance of clinical isolates of S.paratyphi A in Zhengzhou city was rather serious, PFGE patterns showed diversity and dominant characteristics. The PFGE patterns of partial strains and its corresponding anti-drug spectrum have certain relevance and cluster relationship.