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Xinfeng Lu,1,2,* Haijun Guo,2,3,* Xuyong Wei,2,3 Di Lu,2,3 Wenzhi Shu,2,4 Yisu Song,2,4 Nasha Qiu,1,2 Xiao Xu1– 4 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310000, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 4Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao Xu, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China, Email zjxu@zju.edu.cn Nasha Qiu, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China, Email qiunasha@163.comAbstract: With the improvement of the average life expectancy and increasing incidence of obesity, the burden of liver disease is increasing. Liver disease is a serious threat to human health. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, liver transplantation still faces unavoidable difficulties. Mesenchymal stem cells (MSCs) can be used as an alternative therapy for liver disease, especially liver cirrhosis, liver failure, and liver transplantation complications. However, MSCs may have potential tumorigenic effects. Exosomes derived from MSCs (MSC-Exos), as the important intercellular communication mode of MSCs, contain various proteins, nucleic acids, and DNA. MSC-Exos can be used as a delivery system to treat liver diseases through immune regulation, apoptosis inhibition, regeneration promotion, drug delivery, and other ways. Good histocompatibility and material exchangeability make MSC-Exos a new treatment for liver diseases. This review summarizes the latest research on MSC-Exos as delivery vehicles in different liver diseases, including liver injury, liver failure, liver fibrosis, hepatocellular carcinoma (HCC), and ischemia and reperfusion injury. In addition, we discuss the advantages, disadvantages, and clinical application prospects of MSC-Exos-based delivery vectors in the treatment of liver diseases.Keywords: exosomes, mesenchymal stem cells, liver disease, nanocarriers

Tianhui Gao,1,&ast; Cong Yao,1,&ast; Yuanyuan Shang,1 Renchun Su,1 Xuxia Zhang,1 Weicong Ren,1 Shanshan Li,1 Wei Shu,2 Yu Pang,1 Qi Li2 1Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Clinical Center on Tuberculosis Control, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Li; Yu Pang, Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax +86 010 6954 6690 ; +86 10 8950 9366, Email lq0703@hotmail.com; pangyupound@163.comPurpose: Unsatisfactory efficacies of currently recommended anti-Mycobacterium abscessus complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates.Methods: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. A checkerboard method was used to investigate efficacies of various antimicrobial drug combinations.Results: BDQ MICs for MABC isolates ranged from < 0.031 to 1 μg/mL, while MIC50 and MIC90 values were 0.125 μg/mL and 0.25 μg/mL, respectively. TZD MIC50 and MIC90 values for MABC isolates were 1 μg/mL and 4 μg/mL, respectively, which were fourfold lower than corresponding LZD values (P < 0.001). DZD MIC90 values for MABC isolates was 8 μg/mL, which were 0.5-fold lower than corresponding LZD values (P < 0.01). MICs of BDQ, SZD, and LZD for M. abscessus subspecies massiliense isolates were significantly lower than corresponding MICs for M. abscessus subspecies abscessus isolates (P < 0.05). Notably, use of oxazolidinones (DZD, SZD, LZD, or TZD) with BDQ against MABC isolates led to reduction of the oxazolidinone median MIC range from 4 to 0.125 μg/mL to 1– 0.031 μg/mL.Conclusion: These results demonstrated excellent BDQ inhibitory activity against MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections.Keywords: bedaquiline, tedizolid, oxazolidinones, susceptibility testing, Mycobacterium abscessus complex, delpazolid

Plant pathogens are increasingly considered as important agents in promoting plant coexistence, while plant symbionts like ectomycorrhizal fungi (EMF) can facilitate plant dominance by helping conspecific individuals to defend against plant pathogens. However, we know little about their relationships with plants at large scales. Here, using soil fungal data collected from 28 forest reserves across China, we explored the latitudinal diversity gradients of overall fungi and different fungal functional guilds, including putative plant pathogens, EMF, and saprotrophic fungi. We further linked the spatial patterns of alpha diversities of putative plant pathogens and EMF to the variation of plant species richness. We found that the relationships between latitude and alpha diversities of putative plant pathogens and EMF were region-dependent with sharp diversity shifts around the mid-latitude (~35°N), which differed from the unimodal diversity distributions of the overall and saprotrophic fungi. The variations in the diversities of putative plant pathogens and EMF were largely explained by the spatial regions (south vs. north/subtropical zone vs. temperate zone). Additionally, the alpha diversities of these two fungal guilds exhibited opposing trends across latitude. EMF could alter the relationship between diversities of putative plant pathogens and plants in the south/subtropical region, but not vice versa. We also found that the ratio of their alpha diversities (EMF to putative plant pathogens) was negatively related to plant species richness across the spatial regions (north to south), and explained ~10% of the variation of plant species richness. Overall, our findings suggest that plant-microbe interactions not only shape the local plant diversity but also may have non-negligible contributions to the large-scale patterns of plant diversity in forest ecosystems.

Wan Shu, Ziwei Wang, Rong Zhao, Rui Shi, Jun Zhang, Wei Zhang, Hongbo Wang Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Hongbo Wang, Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email hb_wang1969@sina.comBackground: Endometrial cancer (EC) is one of the most common gynecological malignancies, especially in postmenopausal women. Echinacoside (ECH) is a major natural bioactive ingredient derived from Cistanches Herba and Echinacea that has a variety of pharmacological effects. However, the efficacy and the mechanism of ECH against EC have not been elucidated yet.Purpose: A compound-target-disease network was constructed to explore the potential targets and mechanism of ECH against EC. Molecular docking and in vitro experiments further verified the effect of ECH against EC.Methods: The potential targets of ECH against EC were retrieved from multiple public databases. Then, the protein–protein interaction (PPI) network was constructed to screen hub targets. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to discover the potential mechanism. Molecular docking was utilized to verify the binding affinity between hub targets and ECH. Finally, in vitro experiments were conducted to demonstrate the anti-EC effect of ECH.Results: A total of 110 genes were identified as potential targets of ECH against EC. The GO enrichment analysis found that targets were primarily related to oxygen species, apoptosis, and other physiological processes. KEGG pathway analysis showed that PI3K/Akt signaling pathways might play an important role in ECH against EC. Molecular docking indicated that ECH had a significant binding ability with the EGFR, AKT1, ESR1, CASP3, HSP90AA1and MMP9 targets. Results from in vitro experiments revealed that ECH induced apoptosis of Ishikawa and HEC-1-B cells by promoting the arrest of the G2M phase, increasing ROS levels, and decreasing mitochondrial membrane potential (MMP) levels. Furthermore, treatment of ECH significantly reduced the expression levels of PI3K and p-AKT, and the combination of the PI3K inhibitor (LY294002) further enhanced the effects of ECH against EC. The findings suggested that ECH exerted an inhibitory effect on EC cells by inhibiting the PI3K/AKT pathway.Conclusion: Based on network pharmacology, molecular docking technology and in vitro experiments, we comprehensively clarified the anti-EC efficacy of ECH through multiple targets and signal pathways. Furthermore, we provided a novel idea of Traditional Chinese medicine (TCM) against EC.Keywords: endometrial carcinoma, echinacoside, network pharmacology, mechanism, molecular docking

Yanhua Song,1,* Yifeng Ma,2,* Rongmei Liu,1,* Yuanyuan Shang,3,* Liping Ma,1 Fengmin Huo,3 Yunxu Li,3 Wei Shu,4 Yufeng Wang,5 Mengqiu Gao,1 Yu Pang3 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Clinical Laboratory, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 3Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4Clinical Center on TB, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 5Department of Laboratory Quality Control, Innovation Alliance on Tuberculosis Diagnosis and Treatment (Beijing), Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9322Email gaomqwdm@aliyun.comYu PangDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9359Email pangyupound@163.comObjective: A prospective study was conducted to ascertain the accuracy of oral swab specimens collected in the early morning, spot and at night for detecting pulmonary tuberculosis (TB).Methods: We prospectively enrolled patients with symptoms suggestive of pulmonary TB in Beijing Chest Hospital. An early morning sputum specimen was collected from each patient for GeneXpert MTB/RIF (Xpert) and mycobacterial culture. In addition, three oral swabs were collected for TB-LAMP testing.Results: With the combined results of three oral swab specimens, the proportion of Mycobacterium tuberculosis (MTB)-positive cases achieved 40.6%, which was comparable to results for Xpert and MGIT (P=0.603). Using Xpert plus MGIT as reference, the sensitivity of OS-LAMP on a single specimen ranged from 32.6% on the night oral swab to 50.0% on the morning swab. The combination of three oral swab specimens correctly identified 38 MTB-positive cases, indicating an overall sensitivity of 82.6%, which was significantly higher than that of a single oral swab specimen (P< 0.001, P=0.001).Conclusion: Oral swab can be used as an alternative specimen for diagnosis of pulmonary TB using TB-LAMP. Morning oral swab exhibits the highest sensitivity, and the inclusion of more specimens at different time points provides compensation in diagnostic sensitivity with single oral swab.Keywords: diagnosis, oral swab, TB-LAMP, pulmonary tuberculosis, China

The modulation of AMPA receptor (AMPAR) content at synapses is thought to be an underlying molecular mechanism of memory and learning. AMPAR content at synapses is highly plastic and is regulated by numerous AMPAR accessory transmembrane proteins such as TARPs, cornichons, and CKAMPs. SynDIG (synapse differentiation-induced gene) defines a family of four genes (SynDIG1-4) expressed in distinct and overlapping patterns in the brain. SynDIG1 was previously identified as a novel transmembrane AMPAR-associated protein that regulates synaptic strength. The related protein SynDIG4 [also known as Prrt1 (proline-rich transmembrane protein 1)] has recently been identified as a component of AMPAR complexes. In this study, we show that SynDIG1 and SynDIG4 have distinct yet overlapping patterns of expression in the central nervous system, with SynDIG4 having especially prominent expression in the hippocampus and particularly within CA1. In contrast to SynDIG1 and other traditional AMPAR auxiliary subunits, SynDIG4 is de-enriched at the postsynaptic density and colocalizes with extrasynaptic GluA1 puncta in primary dissociated neuron culture. These results indicate that, although SynDIG4 shares sequence similarity with SynDIG1, it might act through a unique mechanism as an auxiliary factor for extrasynaptic GluA1-containing AMPARs. J. Comp. Neurol. 524:2266-2280, 2016. © 2015 Wiley Periodicals, Inc.

Xuezheng Li,1,2 Yunfeng Deng,2 Junling Wang,2 Hui Jing,2 Wei Shu,3 Jingmin Qin,2 Yu Pang,4 Xin Ma1,2 1School of Public Health, Shandong University, Jinan, People’s Republic of China; 2Katharine Hsu International Research Center of Human Infectious Diseases, Shandong Provincial Chest Hospital, Shandong University, Jinan, People’s Republic of China; 3Clinical Center on TB Control, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of ChinaCorrespondence: Yu PangNational Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, No 9, Beiguan Street, Tongzhou District, Beijing 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9359Email pangyupound@163.comXin MaSchool of Public Health, Shandong University, No. 44 Wenhuaxi Road, Lixia District, Jinan 250012, People’s Republic of ChinaTel +86-531-6760 7909Fax +86-531-6760 5715Email mx79@hotmail.comBackground: In this study, we aimed to describe the impact of the Genotype® MTBDRplus line probe assay (LPA) for multidrug-resistant tuberculosis (MDR-TB) on total costs in a high-burden setting in China. The second objective was to evaluate the performance of HAIN on smear-positive sputum and clinical isolates.Methods: All definitive TB inpatients at the Shandong Provincial Chest Hospital between May 2012 and May 2017 were included in the study. Two sputum specimens were collected from each patient to conduct smear microscopy, conventional drug susceptibility testing (DST), and the HAIN test. Laboratory and cost data were collected from the electronic medical record system.Results: A total of 1670 definitive TB patients were included in this study. Of these patients, 1307 (78.3%) had smear-positive/culture-positive tuberculosis, and the remaining 363 (21.7%) had smear-negative/culture-positive tuberculosis. The sensitivity and specificity of the HAIN test for RIF resistance was 94.8% (95% confidence interval [CI]: 91.9–97.6%) and 98.8% (95% CI: 98.3–99.4%), respectively. For INH resistance, the sensitivity and specificity was 89.5% (95% CI: 85.7–93.2%) and 95.6% (95% CI: 94.5–96.7%), respectively. The mean time for detection of MDR-TB in smear-negative cases was determined to be 32 days by the HAIN test, which was significantly shorter than that by conventional DST (56 days). Similarly, the mean time for detection of MDR-TB by the HAIN test was significantly shorter than that by conventional DST in smear-positive cases (3 versus 53 days). In addition, by utilizing the HAIN test, the total health care cost decreased by 71.0% for smear-positive cases and 25.9% for smear-negative cases.Conclusion: In conclusion, our data demonstrate that the HAIN test is an accurate rapid test for detecting both RIF and INH resistance in TB patients. The use of the HAIN test can decrease health care costs and reduce the detection time for MDR-TB patients in China, despite the increased costs for laboratory testing.Keywords: tuberculosis, HAIN, multidrug-resistance, performance, cost

Peijun Tang,1,* Ping Xu,1,* Wei Shu,2 Xiafang Wang,1 Jian Guo,1 Huafeng Song,1 Sumei Li,1 Yu Pang,2 Meiying Wu1 1Department of Tuberculosis, The Fifth People’s Hospital of Suzhou, Suzhou, China; 2National Clinical Laboratory on Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China *These authors contributed equally to this work Background: We performed a prospective study to investigate the association between pre-diagnosis exposure to fluoroquinolone (FQ) and laboratory testing results among tuberculosis (TB) patients. Patients and methods: Each TB-suspected patient provided sputum specimen for mycobacteria growth indicator tube (MGIT) culture and GeneXpert among pulmonary TB patients. Confirmed TB patients and clinically diagnosed TB patients were further enrolled in the final analysis. Results: A total of 661 TB patients were included in the final analysis. The distribution of rural TB patients in the FQ-exposed group was significantly higher than that of urban TB patients (P=0.02). GeneXpert showed significantly better positive rate than MGIT technology for TB cases with prior FQ exposure (30.6% for GeneXpert vs 20.1% for MGIT, P=0.01). The positive rate of GeneXpert was significantly higher than that of MGIT for 7–13 days (P=0.04) and ≥14 days FQ exposure (P=0.01) groups, respectively. We also found that the positive rate of MGIT was significantly decreased from 31.5% for

Jian Zhang,1 Zhisen Shen,1 Huigao Liu,2 Shuai Liu,3 Wenxiu Shu4 1Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Ningbo Zhenhai Longsai Hospital, Ningbo, People’s Republic of China; 3Department of Radiology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, People’s Republic of China; 4Department of Oncology and Hematology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, People’s Republic of China Background: The death-associated protein kinase (DAPK) gene is an important member of the apoptotic pathway and is inactivated by abnormal methylation in numerous cancers, including nasopharyngeal carcinoma (NPC). However, the diagnostic value of DAPK methylation in brushing samples and tissue samples of NPC remains unclear. Methods: We conducted a systematic meta-analysis based on 17 studies (including 386 tissue cases, 233 brushing cases, and 296 blood cases). Results: Our results revealed an association between methylated DAPK and increased risk of NPC in blood, brushing, and tissue samples. In addition, the comparison of the pooled sensitivity, specificity, and area under the curve of methylated DAPK in brushing and tissue samples demonstrated the non-inferior effectiveness of methylated DAPK in brushing samples to monitor the development of NPC. Keywords: death-associated protein kinase, methylation, nasopharyngeal carcinoma, diagnosis

The partitioning and transmutation strategy has increasingly attracted interest for the safe treatment and disposal of high level liquid waste, in which the partitioning of high level liquid waste is one of the critical technical issues. An improved total partitioning process, including a tri-alkylphosphine oxide process for the removal of actinides, a crown ether strontium extraction process for the removal of strontium, and a calixcrown ether cesium extraction process for the removal of cesium, has been developed to treat Chinese high level liquid waste. A test system containing 72-stage 10-mm-diam annular centrifugal contactors, a remote sampling system, a rotor speed acquisition-monitoring system, a feeding system, and a video camera-surveillance system was successfully developed to carry out the hot test for verifying the improved total partitioning process. The test system has been successfully used in a 160 hour hot test using genuine high level liquid waste. During the hot test, the test system was stable, which demonstrated it was reliable for the hot test of the high level liquid waste partitioning.

Nan Wu, Wenna Li, Wenqi Shu, Dalin Jia Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China Abstract: The aim of this study was to determine the effect of picroside II on myocardial ischemia reperfusion injury in rats and to explore its underlying mechanism. Isolated rat hearts underwent 30 minutes of global ischemia followed by 120 minutes of reperfusion. Different doses of picroside II (1 µM, 10 µM, and 100 µM) were given 20 minutes before ischemia. Phosphoinositide 3-kinase inhibitor (wortmannin) and nitric oxide synthase (NOS) inhibitor (L-NG-nitroarginine methyl ester) were given 10 minutes before picroside II treatment. The cardiac function, myocardial infarct size, apoptosis, myocardial nitric oxide content, the expressions of Bcl-2 and Bax, and the activation of the phosphoinositide 3-kinase/Akt/endothelial NOS pathway were evaluated. Treatment with 10 µM and 100 µM picroside II significantly improved postischemic myocardial function, reduced myocardial infarct size, inhibited apoptosis, increased myocardial NO content, upregulated Bcl-2, downregulated Bax, and increased the phosphorylation of Akt and endothelial NOS, but cardioprotection was not shown in the 1 µM picroside II treatment group and was abrogated by wortmannin and L-NG-nitroarginine methyl ester. Furthermore, cardioprotection in the 100 µM picroside II treatment group was superior to that in the 10 µM picroside II treatment group. In conclusion, the data reveals that picroside II has a significant protective effect on myocardial ischemia reperfusion injury in a dose-dependent manner, which was mediated by upregulating the phosphoinositide 3-kinase/Akt/endothelial NOS pathway to increase nitric oxide production and regulating the expressions of Bcl-2 and Bax to inhibit apoptosis. Keywords: picroside II, ischemia reperfusion injury, apoptosis, nitric oxide, endothelial nitric oxide synthase