Src is a non-receptor protein tyrosine kinase activated by a number of extracellular signal moleculars. It is recruited to peripheral sites through myristoylation and the SH3 domain. Src initiates intracellular signal trandsduction pathways that influence cell adhesion, migration, growth, differentiation and survival though catalytic domain. Src is normally maintained in an inactive conformation because of carboxy terminal Src kinase, but can be activated transiently during cellular events such as mitosis or constitutively by abnormal events such as mutation and some cancers. In additions, c-Src protein is found to be highly activated and the Src gene is frequently over-expressed in many cancers. These findings suggest that the relationship between c-Src activation/over-expression and cancer progression appears to be significant.

AIM: To investigate the anti-HIV-1 activity of five anthraquinone derivatives (emodin,rhein,chrysophanol,physcion and aloe-emodin) in vitro.METHODS: Viral replication was estimated by observation of cytopathogenesis and measurement of HIV-1 p24 antigen production in HIV-1ⅢB acutely infected C8166 cells. The anti-HIV-1 activity was evaluated by the 50% effective concentrations (EC50) and selective indexes (SI) of these derivatives.RESULTS: These anthraquinone derivatives inhibited HIV-1ⅢB replication on syncytia formation induced by HIV-1ⅢB infection with EC50 mean values of (11.44±0.93)μmol/L (emodin),(51.28±2.86)μmol/L (rhein),(90.58±2.30)μmol/L (chrysophanol),(8.59±0.38)μmol/L (physcion) and (0.89±0.08)μmol/L (aloe-emodin),respectively. The p24 antigen production with EC50 mean values were (11.61±0.56)μmol/L (emodin),(12.35±4.73)μmol/L (rhein),(39.63±2.87)μmol/L (chrysophanol),>250 μmol/L (physcion) and (2.75±0.20)μmol/L (aloe-emodin) respectively. CONCLUSION: These structurally-related chemicals show different anti-HIV-1 activity in vitro. Among them,aloe-emodin is the most potent inhibitor to HIV-1 replication.

BACKGROUND: Common threewingnut root has the functions of anti-inflammation and immune inhibition, etc., and it has been used at present to treat various autoimmune diseases including rheumatoid arthritis.. Common threewingnut root has complex components, and triptolide is acknowledged as one of the important effective components of common threewingnut root.OBJECTIVE: To establish rat models of type Ⅱ collagen induced arthritis, and observe the effects of triptolide on the contents of interleukin-6,interleukin-10 and tumor necrosis factor alpha (TNF-α) in peripheral serum and synovial fluid.DESIGN: A randomized control animal experiment.SETTING: Department of Integrated Traditional and Western Medicine,Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiments were carried out in the Tongji Hospital from November 2004 to July 2005. Fifty healthy male Wistar rats of clean degree were purchased from the experimental animal center of Tongji Medical College, Huazhong University of Science and Technology [qualification number of animal [scxk(E)2004-2007]. Triptolide (nobatch number because of temporary production) was bought from Fujian Institute of Medical Sciences, and the purity was above 98.5%.METHODS: ① Ten of the 50 rats were randomly selected as the normal controls, and the others were made into models. Type Ⅱ collagen emulsion was injected intradermally at five points along the back and tail of the rats,0.05 mL for each point, and injected intradermally at two points after 15 days. The rats in the normal control group were treated with saline in the same way. The effects of the model establishment were evaluated according to the scoring standards of arthritis index at 30 days after the first immunity, and the rats scored 6 points or above were taken as successful models and enrolled in the experiments. Twenty successful rat models were randomly divided into arthritis model group (n=10) and triptolide treated group (n=10). ② Triptolide (100 mg/L)was dispensed into parenteral solution with propylene glycol (0.05 in volume fraction), and then intramuscularly injected into hindlimb of rats in the triptolide treated group (0.04 mL/100 g), once every three days for 30 days. The rats in the normal control group were given isovolume saline, and those in the arthritis model group were treated with isovolume propylene glycol (0.05 in volume fraction). ③ The materials were removed at 30 days after administration. The contents of interleukin-6, interleukin-10 and TNF-α in peripheral serum and synovial fluid were detected with enzyme-linked immunosorbant assay(ELISA).MAIN OUTCOME MEASURES: The effects of triptolide on contents of TNF-α, interleukin-6 and interleukin-10 in peripheral serum and synovial fluid were observed.RESULTS: Fifty male Wistar rats of clean degree were selected, 10 were used as normal controls, and 20 of the other 40 rats were successfully made isto models and enrolled in the analysis of results. ① The TNF-α contents in peripheral serum and synovial fluid were the highest in the arthritis model group, and obviously decreased after treatment of triptolide [(35.09±8.82), (15.35±3.56) ng/L; (44.17±8.94), (22.54±4.76) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).② The contents of interleukin-6 in peripheral serum and synovial fluid were the highest in the arthritis model group, and were obviously decreased after treatment of triptolide [(76.58 ±6.81), (42.45 ±5.72) rig/L;(88.69±10.56), (48.67±5.97) ng/L; P ＜ 0.01], but did not recover to the levels in the normal control group (P ＜ 0.05). ③ The contents of interleukin-10 in peripheral serum and synovial fluid were the lowest in the arthritis model group, and obviously increased after treatment of triptolide[(17.53±2.07), (21.23±2.91) ng/L; (10.59±2.96), (14.74±1.85) ng/L; P＜ 0.01], which were similar to those in the normal control group (P ＞ 0.05).CONCLUSION: Triptolide can treat arthritis by modulating the contents of cytokines.

Objective To study the clinic manifest-rations, mechanism, diagnosis and treatment of pulmonary arterial hypertention (PAH) in systemic lupus erythamatosus (SLE). Methods The clinic symptoms, laboratory tests. Doppler tests of patients who were diagnosed with PAH and SLE during last five years were analyze retrospectively. Results Anti-RNP antibody's prevalence rate was high. The presence of pulmonary arterial perssure (PAP) was not related to SLE disease active index (SLEDAI). Those who had PAP higher than 45 mm Hg were prone to have Raynaud's phenomenon PAH had no association to auto-antibodies and other systemic lesions. There were no differences in clinic features, auto-antibodies and other examinations between those with kidney injure and without kidney injure. Conclusion PAH may develop insidiously in SLE, so early diagnosis and prompt treatment of PAH can improve the prognosis.

Objective:To analyze the clinical characteristics, etiology and outcome of early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS).Methods:The clinical data of 265 neonates with NS admitted in the neonatal ward of the the Affiliated Hospital of Qingdao University from January 2014 to September 2020 were enrolled, including 76 cases of EONS and 189 cases of LONS. The general information, clinical manifestation, laboratory findings, pathogen distribution, treatment and outcome of the two groups were analyzed with SPSS25.0 statistical software.Results:The rates of meconium-stained amniotic fluid, prenatal maternal fever, abnormal white blood cell (WBC) count and neutrophil count in EONS group were significantly higher than those in LONS group ( P<0.05 or <0.01). However, the rates of indwelling central venous catheters, mechanical ventilation, fever, abdominal distension, abnormal platelet count and serum prealbumin level in LONS group were significantly higher than those in EONS group ( P<0.05 or <0.01). Staphylococcus epidermidis(135/265)and Staphylococcus aureus (22/265) were the most common gram-positive bacteria and Escherichia coli (13/265) was the most common gram-negative bacteria in NS. The proportion of gram-positive bacteria was the highest in both EONS group (85.5%) and LONS group (84.7%), which was mainly Staphylococcus epidermidis of coagulase negative staphylococci. The proportion of Listeria monocytogenes and Streptococcus infections in EONS group was significantly higher than that in LONS group ( P<0.05 or <0.01). The proportion of Staphylococcus aureus infection in LONS group was significantly higher than that in EONS group ( P<0.01). There was no significant difference in case fatality rate between EONS group and LONS group (6.6% vs 2.6%, P>0.05). Conclusions:Perinatal amniotic fluid pollution and prenatal maternal fever are risk factors for the occurrence of EONS, while indwelling central venous catheter and mechanical ventilation are risk factors for the occurrence of LONS. Abnormal platelet count and abnormal serum prealbumin are more common in the LONS group. The bacteria detected in EONS and LONS are mainly Staphylococcus epidermidis. Clinical diagnosis and treatment of EONS and LONS should be managed differently.

Objective:To investigate the clinical risk factors of preterm infants and its severity in premature infants with bronchopulmonary dysplasia (BPD) with retinopathy of prematurity (ROP).Methods:Retrospective clinical study was performed. A total of 126 preterm infants with BPD in the Neonatal Department of the Affiliated Hospital of Qingdao University from January 2016 to December 2018 were enrolled in the study. Among them, 69 were males and 57 were females, whose gestational age<32 weeks and birth weight<1500 g. BPD grades Ⅰ , Ⅱ , and Ⅲ were 63, 40, and 23 cases respectively. According to the presence or absence of ROP, children were divided into ROP group and non-ROP group, with 48 (38.1%) and 78 (61.9%) cases respectively. The differences of clinical data between the two groups were compared and analyzed. Quantitative data comparison between groups was performed by t test, and count data comparison was performed by χ2 test. The risk factors of ROP in BPD premature infants were analyzed by multi-factor logistics regression. The correlation between BPD severity and ROP severity was tested by Spearman rank correlation test. Results:Compared with the non-ROP group, the ROP group had a smaller gestational age ( t=5.988), lower birth weight ( t=7.371), higher the application rate of oxygen concentration> 30% (duration of service> 24 h), high rate ( χ2=17.244) and longer noninvasive ventilation time ( t=-7.139), the differences were statistically significant ( P<0.05). In the logistic regression model, the noninvasive ventilation time was the risk factor for ROP in preterm infants with BPD ( OR≈1.054, P<0.05), while gestational age and birth weight were importantly protective factors for ROP in preterm infants with BPD ( OR≈0.938, 0.996; P<0.05). The results of the correlation analysis found that the severity of BPD was significantly positively correlated with the severity ofROP. As the severity of BPD increased, the severity of ROP increased, and the difference was statistically significant ( rs=0.306, P<0.035). Conclusions:Fetal gestational age, low birth weight, hyperoxia, and long-term non-invasive mechanical ventilation are the main risk factors for ROP in preterm infants with BPD. The severity of BPD is positively correlated with the incidence and severity of ROP.

Objective To compare the three-dimensional （3D） gait characteristics of patients with medial meniscus injury of the knee before and after arthroscopic surgery. Methods Fifteen patients with medial meniscus injury and fifteen healthy subjects were included in the study. The 3D gait parameters were collected, including spatiotemporal parameters, kinematic parameters and kinetic parameters. Results (1) The preoperative walking speed and step length of the injury group were significantly lower than those of the control group. There was no significant difference in walking speed and step length after surgery between the injury group and the control group. (2) In the sagittal plane, the preoperative knee flexion-extension range of motion (ROM), the maximum flexion angle in load-bearing phase and swinging phase were significantly lower than those in the control group (P＜0.001). The maximum knee flexion in load-bearing response phase was significantly increased after surgery (P＜0.05), but the maximum flexion angle in swing phase and the knee flexion-extension ROM after surgery were still significantly lower than those of the control group (P＜0.05). In the coronal plane, the preoperative knee adduction-abduction ROM and the maximum adduction angle in gait cycle were significantly lower than those of the control group (P＜0.001). The postoperative parameters significantly increased compared with the preoperative ones (P＜0.05), but they were still significantly lower than those of the control group (P＜0.001). (3) In the sagittal plane, the postoperative first and second peaks of knee flexion moment in stance phase of the injury group increased, compared with the preoperative ones (P＞0.05), but they were still significantly lower than those of the control group (P＜0.05). In the coronal plane, the postoperative first and second peaks of knee adduction moment in stance phase of the injury group increased, compared with preoperative ones, but they were also significantly lower than those of the control group (P＜0.05). Conclusions Patients with medial meniscus injury have their own unique gait patterns, usually with stiffening gait to reduce the knee load. Arthroscopic meniscusplasty can significantly improve knee gait characteristics, but patients still cannot return to normal gait in a short period of time.

Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.

OBJECTIVE：To stud y the effects of sinapine thiocyanate （ST） on the proliferation ，epithelial mesenchymal transformation（EMT）and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells，and to investigate its possible mechanism. METHODS ：Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group （0.1％ DMSO） and ST different concentration groups （5，10，20 μmol/L）. CCK- 8 assay，5-ethynyl-2′-deoxyuridine（EDU）test， scratch test and Transwell chamber invasion test were adopted to test the proliferation ，migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group （0.1％ DMSO），ST group （20 μmol/L），ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155（EGFR agonist ）] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79（PI3K/Akt agonist ）]. The proliferation ，migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay，scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor （EGFR），phosphatidylinositol 3 kinase（PI3K），phosphorylated phosphatidylinositol 3 kinase（p-PI3k），protein kinase B （Akt）and phosphorylated protein Akt （p-Akt）protein of cells in blank control group and ST different concentration groups（5，10，20 μmol/L）were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group （0.1％ DMSO），ST group （20 μmol//L），ZD1839 group（positive control ，20 μmol//L，EGFR inhibitor ）and LY 294002 group（positive control，20 μmol//L，PI3K/Akt inhibitor ）. CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS ：Compared with blank control group ，the proliferation ，migration and invasion ability of SCL- 1 cells were significantly decreased in 5，10，20 μmol/L ST groups（P＜0.05）. Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5，10，20 μmol/L ST groups（P＜0.05），while the protein expression of E-cadherin was increased significantly （P＜0.05）；the protein expressions of EGFR ，p-PI3K and p-Akt were significantly decreased （P＜0.05）. Compared with ST group ，the proliferation ，migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group （P＜0.05）. Compared with blank control group ，the proliferation ability of WS 1 cells had no significant change in ST group ，while the proliferation ability of SCL- 1 cells was decreased significantly （P＜0.05）；the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group（P＜0.05）. Compared with ST group ，the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group（P＜0.05），but there was no significant difference in the proliferation ability of SCL- 1 cells （P＞0.05）. CONCLUSIONS ：ST may inhibit the proliferation ，EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ，and its side effects are few.