CD38 is a multifunctional enzyme expressed in a variety of mammalian tissues, its catalytic activity was involved in a wide range of physiological processes. Based on the reported inhibitor of human CD38 NADase, 33 purine derivatives were designed and synthesized. The biological activity assay showed that compounds 20 and 38 exhibited almost the same extent of inhibitory activities on human CD38 NADase as the lead compound H2. The results also revealed that small substituents at C-6 of purine ring gave no obvious effect on inhibitory activity, but phenylpropionyl moiety at N-2 could affect the binding mode of the compound with CD38. This study provides a reliable basis for future rational design of inhibitors for CD38.

ObjectiveTo explore the hospital information system (HIS) failure response capacity of medical staffs in Xi'an and provide evidences for hospitals to carry out individual education and guidance. MethodsSelf-designed general information and HIS failure response capacity questionnaires were used to investigate 210 medical staffs from three tertiary hospitals in Xi'an.Results Knowledge level of HIS failure response in medical staffs was general and their pass rate of the test was 62.9%. Univariate analysis showed that there was significant difference in the pass rate of staffs with different education level,HIS failure experiences and HIS failure related education experience (χ2=7.027,8.842,5.484;P<0.05). Binary logistic regression analysis showed that education level,working experience,hospital information system failure experience and HIS failure related education experience were main influencing factors of HIS failure response capacity of medical staffs.Conclusions The current HIS failure education system is not perfect in our country and the hospital information system failure response knowledge and capacity of medical stuffs should be improved. Hospitals could carry out various forms of education and training to improve the HIS failure response capacity of medical staffs.

Objective To explore the knowledge of occupational hazards and protection in vocational nursing students in Xi'an City, and to provide evidences for targeted education and guidance. Methods From January to June 2016, a total of 287 nursing students from 3 vocational colleges in Xi'an City were selected by stratified sampling method and investigated with "occupational hazards and protection knowledge questionnaire". Results The pass rate of occupational hazards and protection knowledge in nursing students was 53.0%. It was indicated that education level, parents' occupation, internship experience and nursing occupational hazards related education experience were the factors influencing occupational hazards and protection knowledge (P<0.01). Conclusions The current nursing occupational hazards and protection education system were not perfect in our country and it should be improved in nursing students. Meanwhile, schools can carry out various forms of education and training.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.
Animals ; Apoptosis ; Calcium/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; Hepatocyte Growth Factor/metabolism* ; Lipopolysaccharides/pharmacology* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Mice ; Mitochondria/metabolism* ; Oxidative Stress ; Reactive Oxygen Species/metabolism* ; Respiratory Distress Syndrome ; Sirolimus/pharmacology* ; TOR Serine-Threonine Kinases/metabolism*

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

Objective:To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China.Methods:Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio ( HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results:Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion:Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

Pinellia ternata is an important medicinal plant, and its growth and development are easily threatened by high temperature. In this study, comprehensive research on physiological, cytological and transcriptional responses to different levels of heat stress were conducted on a typical phenotype of P. ternata. First, P. ternata exhibited tolerance to the increased temperature, which was supported by normal growing leaves, as well as decreased and sustained photosynthetic parameters. Severe stress aggravated the damages, and P. ternata displayed an obvious leaf senescence phenotype, with significantly increased SOD and POD activities (46% and 213%). In addition, mesophyll cells were seriously damaged, chloroplast thylakoid was fuzzy, grana lamellae and stroma lamellae were obviously broken, and grana thylakoids were stacked, resulting in a dramatically declined photosynthetic rate (74.6%). Moreover, a total of 16 808 genes were significantly differential expressed during this process, most of which were involved in photosynthesis, transmembrane transporter activity and plastid metabolism. The number of differentially expressed transcription factors in MYB and bHLH families was the largest, indicating that these genes might participate in heat stress response in P. ternata. These findings provide insight into the response to high temperature and facilitate the standardized cultivation of P. ternata.
Pinellia/genetics* ; Heat-Shock Response/genetics* ; Photosynthesis/genetics* ; Plants, Medicinal/genetics* ; Phenotype