Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.

ObjectiveTo observe the effects of Cuscutae Semen on the learning and memory ability， N6-methyladenosine （m⁶A）-related modification enzymes and total m⁶A level in hippocampus of the offspring of fear-damaged pregnant rats. MethodForty-five pregnant rats were randomly divided into blank group， model group and Cuscutae Semen group. From the 1^st day to the 19^th day of pregnancy， rats in the model group and the Cuscutae Semen group were induced by observing electric shock of other rats. The Cuscutae Semen group was treated with 5 g·kg^-1·d^-1 Cuscutae Semen decoction （ig）， while the other two groups were treated with the same amount of purified water. The offspring were assigned following the grouping method of their maternal generation. The behavioral changes of the offspring were tested by Morris water maze on 21^st day after birth， and the development of hippocampal neurons was observed by transmission electron microscopy. The mRNA and protein expression levels of methyltransferase-like 3 （METTL3）， METTL14， Wilms tumor 1 associated protein （WTAP）， fat mass and obesity-associated protein （FTO） and Alk B homologue 5 （ALKBH5） were detected by Real-time polymerase chain reaction （Real-time PCR）， Western blot and immunohistochemistry （IHC）. The total content of m⁶A in hippocampus was determined by high performance liquid chromatography tandem mass spectrometry （LC-MS/MS）. ResultCompared with the conditions in the blank group， the average latency duration in the model group was prolonged， and the number of entries in the target quadrant， the target quadrant duration and the number of crossing the platform were decreased （P<0.01）. Additionally， the model group had seriously damaged structure of hippocampal CA1 and CA3 neurons， swollen mitochondria， expanded endoplasmic reticulum， and small number of synapses with some having blurred structure， and the expression levels of METTL3， METTL14， FTO， ALKBH5 as well as the total m⁶A level were lower than those in the blank group （P<0.05，P<0.01）. Compared with the model group， the Cuscutae Semen group had shortened average latency duration， increased number of entries in the target quadrant， target quadrant duration and number of crossing the platform （P<0.01）， alleviated damage of hippocampal CA1 and CA3 neurons， fine structure of mitochondrial and endoplasmic reticulum， and clear， intact and dense synapses. And the expression levels of METTL3， METTL14， FTO as well as the total level of m⁶A were up regulated， while the expression level of ALKBH5 was down regulated in the Cuscutae Semen group （P<0.05，P<0.01）. ConclusionCuscutae Semen improved the learning and memory ability of the offspring of the rats affected by fear damaging kidney during pregnancy， protected hippocampal neurons， and up-regulated the expression levels of METTL3， METTL14， FTO and the total m⁶A level in hippocampus.

Objective: To observe the effects of the tofacitinib on interstitial lung disease( ILD) by regulating the JAK⁃STAT signaling pathway. Methods: Wistar rats were randomly divided into 4 groups:normal group , ILD group ,prednisone acetate group , and tofacitinib group. Except for the normal group , the other three groups were given 3mg/ml bleomycin solution for modeling. After 28 days of intragastric administration , the lung tissues of all rats were collected for hematoxylin⁃eosin staining ( HE) and Western blot ( WB) to detect the protein levels of JAK1 and STAT1;Enzyme⁃linked immunosorbent assay(ELISA) was used to detect tumor necrosis factor in rat serum (TNF) Ⅳ α , interleukin (IL) Ⅳ6 , IL⁃10 , IL⁃1β . Results : HE staining of lung tissue in ILD ,prednisone acetate group and tofacitinib group showed alveolar tissue thickening , alveolar wall capillary congestion , bronchial luminal epithelial cells shedding, and inflammatory cell exudation. The results of WB showed that JAK1 and STAT1 significantly increased in ILD group , and decreased in different degrees compared with ILD group , tofacitinib group and prednisone acetate group (P < 0. 05) . The ELISA results showed that the expressions of serum TNF⁃α , IL⁃6 and IL⁃1β in the ILD group were significantly higher than those in the normal group (P < 0. 01) . The expression of pine group decreased (P < 0. 05) , and the expression of IL⁃10 was the opposite. Conclusion Tofacitinib reduces lung tissue damage and the inflammatory response in the treatment of ILD by inhibiting the JAK⁃STAT pathway and down⁃regulating the expression of inflammatory factors TNF⁃α , IL⁃6 , IL⁃1β and up⁃regulating the anti⁃inflammatory factor IL⁃10.

Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death (ICD) to provoke a robust immune response for metastasis control. Here, a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation, chemodynamic (CDT) and photothermal therapy. Ultrasmall FeS-GOx nanodots were synthesized with glucose oxidase (GOx) as template and induced by paclitaxel (PTX) to form self-assembling FeS-GOx@PTX (FGP)

Objective: To analyze the sensory processing characteristics among preschoolers with mental health problems in Nanshan District, Shenzhen. Methods: Random cluster sampling was used to select kindergartens for psychological screening from March to June 2018. The Strengths and Difficulties Questionnaire (SDQ) and the Simplified Sensory Questionnaire (SSP) were used to evaluate 6 365 preschool children. Results: A total of 15.15% preschoolers were detected with abnormal results. The SSP scores of preschoolers with emotional symptoms/conduct problems/prosocial behaviors were lower than normal preschoolers’(P<0.01). Among the preschoolers with hyperactivity-inattention, taste/smell sensitivity (F=12.45)/underresponsive/seeks sensation(F=102.44), auditory filtering(F=93.51), low energy/weak(F=13.33), visual/auditory sensitivity (F=4.32) scores were lower than normal preschoolers’(P<0.05), the scores of tactile sensitivity movement sensitivity were no statistical difference with normal preschoolers’. Among the preschoolers with peer problem, taste/smell sensitivity(F=5.86), tactile sensitivity(F=6.05), movement sensitivity(F=4.70), auditory filtering(F=17.32), low energy/weak (F=9.56), visual/auditory sensitivity (F=4.16) scores were lower than normal preschoolers’ (P<0.05), and the scores of under-esponsive/seeks sensation were no statistical difference with normal pre-schoolers’. Prosocial behavior and tactile (r=0.30), under-responsive/seeks sensation(r=0.37), auditory filtering(r=0.37), low energy/weak (r=0.31) were positive associated(P<0.01). Emotional symptoms were negatively associated with lack of energy/weakness(r=-0.33, P<0.01). Conclusion Mental health problems are related to sensory processing ability in preschoolers. Preschoolers with mental health problems have weak sensory processing ability. Clinicians and occupational therapists should pay attention to evaluation and intervention of sensory processing ability in preschoolers with mental health problems.

Objective To compare the effects of transcutaneous electrical acupoint stimulation ( TEAS) combined with general anesthesia and epidural block combined with general anesthesia on the re-covery of patients undergoing laparoscopic radical resection of colorectal cancer. Methods Eighty-four pa-tients of both sexes, aged 35-64 yr, with body mass index of 18-25 kg∕m2 , of American Society of Anes-thesiologists physical status Ⅱ or Ⅲ, scheduled for elective laparoscopic radical resection of colorectal cancer, were divided into 3 groups (n=28 each) using a random number table method: general anesthesia group (group G), TEAS combined with general anesthesia group (group TG), and epidural block com-bined with general anesthesia group ( group EG) . In group TG, patients received continuous TEAS of bilat-eral Neiguan, Hegu, Zusanli, Shangjuxu and Xiajuxu acupoints starting from 30 min before anesthesia in-duction until the end of surgery at a frequency of 2∕100 HZ and intensity of 3-8 mA with disperse-dense waves. In group EG, an epidural catheter was placed at L1,2 and advanced for 3 cm in the epidural space in cephalad direction, 2％ lidocaine 3 ml was given as a test dose, 0. 375％ ropivacaine 6-10 ml was injected into the epidural space, the level of anesthesia was adjusted to T6 , and then 0. 375％ ropivacaine 5 ml∕h was infused to the epidural space until the end of operation. Patients were endotracheally intubated after rou-tine induction of general anesthesia and mechanically ventilated, and combined intravenous-inhalational an-esthesia was used to maintain anesthesia. The Quality of Recovery ( QoR-15) score was recorded on 1 day before surgery and 1-3 days after surgery. The development of nausea and vomiting, cognitive decline and requirement for rescue analgesics was recorded within 3 days postoperatively. The intraoperative consump-tion of remifentanil and propofol, vasoactive drugs, extubation time, time of PACU stay, time of passing flatus and length of postoperative hospital stay were recorded. Results Compared with group G, the con-sumption of remifentanil was significantly decreased, the QoR-15 scores were increased at 1-3 days after surgery, the incidence of nausea and vomiting and cognitive decline was decreased, and the extubation time, time of passing flatus and length of postoperative hospital stay were shortened in group TG and group EG ( P<0. 05) . Compared with group TG, the intraoperative requirement for vasoactive drugs was signifi-cantly increased in group EG ( P<0. 05) . Conclusion TEAS combined with general anesthesia and epi-dural block combined with general anesthesia have the comparable effect on the recovery of patients undergo-ing laparoscopic radical resection of colorectal cancer, however, the former one provides more stable hemo-dynamics during surgery.

To construct recombinant eukaryotic expression plasmid vector of human IL-34 gene, and to study the effects of IL-34 expressed by human bone marrow-derived mesenchymal stem cells (hBM-MSCs) on THP-1 cells. Full-length IL-34 encoding sequence was amplified by PCR. And this fragment was cloned into the plasmid pIRES2-EGFP. Western blotting and ELISA were used to analyze the expression of IL-34 in hBM-MSCs. THP-1 cells were cultured with hBM-MSCs medium containing IL-34 protein. Real-time PCR detected the effects of IL-34 on the expression of IL-10 and TNFα in THP-1 cells. Restrictive enzyme analysis and sequencing demonstrated that IL-34 eukaryotic expression vector was successfully constructed. IL-34 protein expressed by hBM-MSCs could promote IL-10 and TNFα expression in THP-1 cells. Those results show that IL-34 expressed by hBM-MSCs has regulating effect on THP-1 cells.

Objective To investigate the effect of Miao medicine Jinwu Jiangu decoction containing serum freeze-dried powder on levels of IL-17,ACT1 and TRAF6 in human rheumatoid arthritis fibroblast like synoviocytes (RA-HFLS).Methods Rabbits were randomly divided into blank control group (recieving normal saline of the same volume),Jinwu Jiangu decoction high-dose,medium-dose and low-dose group (intragastrically administrated with Jinwu Jiangu decoction at doses of 14.4,4.8 and 2.4 g·kg-1,respectively),tripterygium glycosides group and prednisone group (treated with human equivalent dosage).RA-HFLS primary cell model was established in the experiment.ELISA method was used to detect effect of lyophilized powder on IL-17 secretion.Expression of ACT1,TRAF6 mRNA was detected by RT-PCR.Results Compared with the blank control gorup,IL-17 in the supernatant of each medication administration group was significantly decreased (all P<0.01),and it was decreased most significantly in Jinwu Jiangu decoction high-dose and medium-dose group.IL-17 was down-regulated more significantly in high-dose group than that in tripterygium glycosides group (P<0.01).Compared with the blank control group,TRAF6 and ACT1 mRNA expression level of each medication administration group were significantly decreased (all P<0.01),and in the high-dose group that were decreased most significantly,but not significantly different as compared with tripterygium glycosides group and prednisone group (P>0.05).Conclusion Freeze-dried powder of Jinwu Jiangu decoction can decrease the secretion of IL-17 and down-regulate expression of ACT1,TRAF6 with RA-HFLS.

Pulmonary surfactant (PS) is synthesized and secreted by alveolar epithelial type II (AEII) cells, which is a complex compound formed by proteins and lipids. Surfactant participates in a range of physiological processes such as reducing the surface tension, keeping the balance of alveolar fluid, maintaining normal alveolar morphology and conducting host defense. Genetic disorders of the surfactant homeostasis genes may result in lack of surfactant or cytotoxicity, and lead to multiple lung diseases in neonates, children and adults, including neonatal respiratory distress syndrome, interstitial pneumonia, pulmonary alveolar proteinosis, and pulmonary fibrosis. This paper has provided a review for the functions and processes of pulmonary surfactant metabolism, as well as the connection between disorders of surfactant homeostasis genes and lung diseases.
ATP-Binding Cassette Transporters ; genetics ; DNA-Binding Proteins ; genetics ; Homeostasis ; Humans ; Lung Diseases ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism ; Transcription Factors

Objective To analyze hemolysin and virulence -related genes in incomplete hemolytic Staphylococcus aureus.Methods Fifty strains of incomplete hemolytic Staphylococcus aureus were isolated from patients admitted in the Second Affiliated Hospital of Soochow University during 2013 and 2014, and the isolates with complete hemolytic phenotype were also collected at the same period as the control strains . All the strains were inoculated and subcultured on four kinds of sheep blood agar plates supplied by different manufacturers to compare their hemolytic phenotype .The relative mRNA expressions of hemolysin genes (hla, hlb, hlc, hld) in standard strain, complete and incomplete hemolytic phenotype strains were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and valued by 2 -△△Ct method.t test was used to compare mRNA expressions of hemolysin genes .Western blot was performed to analyze the expression of α-hemolysin.Antibiotic susceptibility test of incomplete hemolytic strains was performed using broth microdilution method.Resistant gene mecA and virulence genes pvl, tst were detected by PCR.Results The steady and hereditary incomplete hemolysis was observed in 50 strains of incomplete hemolytic Staphylococcus aureus on the sheep blood agar plates from different suppliers .Taking mRNA expression of hla, hlb, hlc, hld in standard strain as 1, the relative mRNA expressions of hemolysin genes in incomplete hemolytic strains were 0.02, 7.51, 0.06 and 0.12 respectively, there were statistical differences between standard strain and incomplete hemolytic strains (t =8.46, -56.40, 8.12 and 7.61, all P <0.05).And the expression of α-hemolysin was decreased in incomplete hemolytic strains .All the strains were identified as methicillin resistant Staphylococcus aureus (MRSA).Three strains exhibited different minimum inhibitory concentrations of teicoplanin and linezolid after subcultured , but the differences had no impact on the final results of antibiotic susceptibility test .mecA, pvl and tst genes were positive in incomplete hemolytic strains . Conclusion Staphylococcus aureus with incomplete hemolytic phenotype is methicillin resistant with higher expression of β-hemolysin and lower expressions of α-hemolysin, γ-hemolysin and δ-hemolysin.It carries plv and tst virulence genes and is of high virulence .