Objective To research and develop a kind of puncture needle depth -controlled device. Methods Based on mechanical design principle, and with stainless steel and plexiglass as materials, the puncture needle depth -controlled device is composed of syringe, needle guard, pin pusher, scale gauge, depth-controlled nut, and locking screw and pedestal hood. Results The puncture needle depth-controlled device is suitable for different kinds of puncture needles and syringe needles, and has many advantages including operation labor -saving, controlling depth, diminishing contamination and infection, avoiding needle guard slippage and needle bending. The operation can be implemented in one minute. Conclusion The kind of puncture needle depth-controlled device is developed successfully and as new first-aid equipment is provided for war wounds or accidents scene rescue.

AIM To investigate the role of serine/threonine protein phosphatases 1 and 2A (PP1/2A) in regulation of cell signal transduction involved in the tolerance of human umbilical vein endothelial cells (HUVEC) to hypoxia. METHODS HUVEC tolerance was established by hypoxic preconditioning. The tolerance of HUVEC was evaluated by the cell survival rate, lactic dehydrogenase (LDH) releasing and total antagonistic-oxidative capability (T-AOC). Subcellular localization of nuclear factor E2-related factor 2 (Nrf2) was determined by immunocytochemistry combined with Western blot. The expression of stress protein of heme oxygenase-1 (HO-1) was measured by Western blot. RESULTS Hypoxia 90 min decreased the survival rate and T-AOC of HUVEC significantly, increased the release of LDH in cultured HUVEC. Compared with the hypoxic group, hypoxic preconditioning (4, 8 and 24 h after hypoxia 10 min) up-regulated the tolerance against hypoxia in HUVEC, the survival rate of HUVEC and T-AOC increased and the release of LDH down-regulated when insulted with hypoxia (90 min) in HUVEC. Hypoxic preconditioning established the translocation of Nrf2 from cytoplasm to nucleus and up-regulated the expression of downstream protein HO-1. Pretreatment with okadaic acid (40 nmol·L-1), a powerful inhibitor of PP1/2A, for 10 min in hypoxic preconditioning HUVEC partly inhibited the translocation of Nrf2 from cytoplasm to nucleus and the expression of HO-1, abolished the tolerance of HUVEC established by hypoxic preconditioning. CONCLUSION PP1/2A at least partly take part in Regulation of translocation of Nrf2 and expression of HO-1, with is associated with the tolerance of HUVEC established by hypoxic preconditioning.

Objective To investigate the clinical significance.of thrombocytopenia in systemic lupus erythematosus (SLE).Methods One hundred and two SLE patients with thrombocytopenia who were admitted to Peking University People's Hospital were involved in the study.SLE patients without thrombocytopenia were controls.Clinical and laboratory characteristics were analyzed.T-test and Chi-square test were used for inter-group comparison.Results Patients with thrombocytopenia had more organ damage than those without,although the disease activities (SLEDAI) were not different between these two groups.Bone marrow characteristics were analyzed and 16 patients were amegakaryocytic.However,there were no differences observed between patients with amegakaryocytosis and normal megakaryocytes in organ damage,disease activity and response to therapy.Conclusion Lupus patients with thrombocytopenia usually have more organ damage.About 32％ of those patients are amegakaryocytosis.

AIM: To study the effects of hypertonic NaCl-NaAc on microcirculation in hemorrhage-shocked rats.METHODS: SD rats were randomized into three groups of 7 5% NaCl(hypertonic saline, HS),5% NaCl-3 5% NaAc(hypertonic sodium acetate, HSA) and 0 9% NaCl(normal saline, NS) 4 mL/kg HS,HSA or NS was given intravenously following hemorrhagic shock The microcirculation of spinotrapezius muscle was observed RESULTS: HS increased mean aortic pressure more significant than HSA Variables including arteriolar and venular diameter,velocity and volumetric flow rate and open capillaries were increased and erythrocyte aggregation was decreased in 5 min after resuscitation with both HS and HSA solutions 5 min later,variables were deteriorated in HS group After local treatment, arteriolar and venular diameters were dilated significantly in HSA group CONCLUSION:HSA had superior effects to HS in improving microcirculation of hemorrhage-shocked rats

Objective To compare the clinical efficacy of ibuprofen arginate,a new nonsteroidal antiinflammatory drug,with that of ibuprofen,in patients with rheumatoid arthritis or knee osteoarthritis and to evaluate the safety and tolerability of ibuprofen argihate.Methods This is a muhicenter,random,open,active comparator-controlled,parallel clinical trail in which 171 patients with rheumatoid arthritis or knee osteoarthritis were enrolled.Patients were randomized to 2 groups:400 mg of ibuprofen arginate three times daily and 400 mg of ibuprofen three times daily respectively.Clinical efficacy and safety were evaluated after 4-week treatment.Results Ibuprofen arginate,at dosages of 400 mg three times daily,had shown significant efficacy in relieving pain,tenderness and swelling of joints and there was no significant difference when compared to that of ibuprofen.There was no difference in clinical adverse effects between the two groups and no serious adverse effects were repofled.But ibuprofen arginate could initiate effectiveness more rapidly than ibuprofen in both rheumatoid arthritisand osteoarthritis patients.Conclusion Ibuprofen arginate has the same clinical efficacy and safety profiles as itmprofen in treating rheumatoid arthritis and osteoarthritis.However,its onset is more rapid than ibuprofen.

This study aimed to observe the therapeutic effect and mechanism of Jinshuibao tablet on acute renal injury induced by cisplatin. Acute renal injury models in SD rats were induced separately by single intraperitoneal injection of cisplatin(5 mg/kg)and intravenous injection for 5 consecutive days at a dosage of 2 mg/kg per day. The renal function and renal histopathological changes were observed in rat acute renal injury models after prevention and treatment with Jinshuibao tablet, respectively. The content of tumor necrosis factor(TNF-α)and reactive oxygen species(ROS), the activity of Caspase 3 and the expression of t-p38, p-p38, Bax and Bcl-2 in the kidneys were detected. The results showed that preventive and therapeutic administration of Jinshuibao tablets could both significantly inhibit the increase of the blood urea nitrogen(BUN)and creatinine(CRE), increase the creatinine clearance rate, reduce the contents of TNF-α and ROS, and decrease the activity of Caspase 3 in acute renal injury models induced by cisplatin. The renal histopathological results showed that Jinshuibao tablets could significantly reduce renal histopathology scores, ameliorate renal tubule degeneration and inflammatory infiltration. Western blot results showed that Jinshuibao tablets could significantly decrease the expression of t-p38 and p-p38, while increasing the Bcl-2/Bax ratio in the kidneys. These results suggested that preventive and therapeutic administration of Jinshuibao tablets could both improve renal function and pathological changes of renal tissue, which might be related to the inhibition of TNF-α and the ROS-p38 MAPK-Caspase3 pathway and thus inhibition of apoptosis.

Background::Response to immune checkpoint inhibitors (ICIs) is affected by multiple factors. This study aimed to explore whether sites of metastasis are associated with clinical outcomes of ICIs in advanced non-small-cell lung cancer (NSCLC) patients.Methods::The data of NSCLC patients with high programmed death-ligand 1 expression and good performance status receiving first-line ICIs monotherapy from Guangdong Provincial People’s Hospital between May 2019 and July 2020 were retrospectively analyzed. Metastatic sites included liver, bone, brain, adrenal gland, pleura, and contralateral lung. Progression-free survival (PFS) and overall survival (OS) were compared between different metastatic sites and metastatic burden by the Kaplan-Meier method. Organ-specific disease control rate (OSDCR) of different individual metastatic sites was evaluated.Results::Forty NSCLC patients meeting the criteria were identified. The presence of liver metastasis was significantly associated with shorter PFS (3.1 vs. 15.5 months, P = 0.0005) and OS (11.1 months vs. not reached, P = 0.0016). Besides, patients with bone metastasis tend to get shorter PFS (4.2 vs. 15.5 months, P = 0.0532) rather than OS ( P = 0.6086). Moreover, the application of local treatment could numerically prolong PFS in patients with brain metastasis (15.5 vs. 4.3 months, P = 0.1894). More metastatic organs involved were associated with inferior PFS ( P = 0.0052) but not OS ( P = 0.0791). The presence of liver metastasis or bone metastasis was associated with more metastatic organs (Phi[φ]: 0.516, P = 0.001). The highest OSDCR was observed in lung (15/17), and the lowest in the liver (1/4). Conclusions::Metastases in different anatomical locations may be associated with different clinical outcomes and local tumor response to ICIs in NSCLC. ICIs monotherapy shows limited efficacy in patients with liver and bone metastasis, thus patients with this type of metastasis might require more aggressive combination strategies.

Objective This study established a model of invasive Aspergillus niger lung disease in immunosuppressed rats to provide theoretical support for the pharmacodynamic evaluation of anti-invasive pulmonary aspergillosis drugs and mechanism studies.Methods Sixty SD rats were randomly divided into a normal control group;cyclophosphamide control group,and cyclophosphamide+fungal infection low,medium,and high dose groups,with 12 animals in each group.General clinical observations were performed daily,and the serum levels of immunoglobulin(Ig)G and IgM and galactomannan(GM)were detected by ELISA on the 3rd and 7th days of modeling.Simultaneously,the ratio of CD4+and CD8+cells,content of white blood cells(WBCs)and neutrophils(Neu)in peripheral blood,the Aspergillus niger load in alveolar lavage,and morphological changes to rat lung tissue were observed.Results Rats in the cyclophosphamide control and cyclophosphamide+fungal infection groups showed reduced voluntary activity and erect hair after modeling,and rats in the cyclophosphamide+fungal infection group also had shortness of breath and audible wet rhonchi in the lungs.Compared with the normal control group,rats in the cyclophosphamide control group showed significant reductions in the levels of CD4+,WBC,Neu,IgG,and IgM in the blood,and their proportion of CD8+cells was significantly higher(P＜0.05,P＜0.01).Compared with the cyclophosphamide control group,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly reduced blood levels of IgG,IgM,and CD4+cells(P＜0.05,P＜0.01);while the cyclophosphamide+fungal infection low-,medium-,and high-dose groups had significantly reduced blood levels of WBC and Neu(P＜0.05,P＜0.01).Additionally,rats in the cyclophosphamide+fungal infection medium-and high-dose groups had significantly increased blood CD8+cells(P＜0.05,P＜0.01),Blood GM levels and the alveolar lavage Aspergillus niger load were significantly increased in rats in the cyclophosphamide+fungal infection low-,medium-,and high-dose groups compared with the cyclophosphamide control group(P＜0.05,P＜0.01).The lung tissues of the cyclophosphamide+fungal infection low-,medium-,and high-dose groups showed mycelial distribution and destruction of alveolar epithelium,increase of bronchial epithelial cup cells in the alveoli,and infiltration of inflammatory cells,and the degree of lesions was positively correlated with the modeling dose.Conclusions In this study,we used Aspergillus niger combined with cyclophosphamide immunosuppressant to construct a model of invasive Aspergillus niger lung disease.The duration of the disease was positively correlated with the concentration of bacterial fluid and modeling time,confirming that cellular immunity plays an important role in the pathogenesis of the disease.At the same time,Ig can also affect the development of invasive pulmonary aspergillosis,and it is speculated that the pathogenesis may be related to the level of Ig produced by humoral immunity.

As a new beer fermentation technology, high temperature and high gravity fermentation has brought many benefits to brewery industry, but there are also a series of problems such as the decrease of yeast flocculation ability at the end of fermentation and the high concentration of higher alcohols. To increase yeast flocculation ability and reduce the production of higher alcohols in high temperature and high gravity fermentation of beer, BAT2 was replaced by the FLO5 expression cassette to obtain the mutant strain S6-BF2. Real-time quantitative PCR showed that the relative transcriptional level of FLO5 in S6-BF2 improved 17.8 times compared with that in S6. The flocculation ability of mutant S6-BF2 heightened by 63% compared to that of the original strain S6, and the concentration of higher alcohols decreased from 175.58 mg/L to 159.58 mg/L in high temperature and high gravity fermentation of beer. Moreover, the activity of mitochondrial branched-chain amino acid transferase was repressed, resulting in the production of higher alcohols of 142.13 mg/L, reduced by 18.4% compared to that of the original strain S6, meanwhile, the flocculation ability of mutant S6-BF2B1 kept unchanged compared to the mutant S6-BF2. The determination result of flavor compounds showed that the higher alcohols/ester ratio in beer was reasonable. This research has suggested an effective strategy for enhancing yeast flocculation ability and decreasing production of higher alcohols in high-temperature and high-gravity brewing.
Beer ; Fermentation ; Hypergravity ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae Proteins ; Temperature ; Transaminases

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC₅₀: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC₅₀: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.