Signal transducer and activator of transcription 3(STAT3)is an intracellular signaling factor that plays a critical role in various cellular processes,including the growth,differentiation,apoptosis,and immune response of cells.Aberrant activation of T helper cell 17(Th17)is closely associated with the morbidity and progress of various autoimmune diseases.STAT3 participates in the pathogenesis of Sj?gren syndrome by inducing excessive proliferation and abnormal differentiation of Th17 cells and affecting lymphocyte infiltration into exocrine glands.Therefore,targeting the STAT3 signaling pathway represents a potential novel therapeutic approach for the treatment of Sj?gren syndrome.This review summarizes the research of STAT3 in the pathogenesis and progression of Sj?gren syndrome through regulating Th17 cells,focusing on current inhibitors targeting the STAT3 signaling pathway as potential therapeutic targets for Sj?gren syndrome.

Objective:To investigate the effect of a degradable high-purity magnesium screw in fixing the greater trochanter bone flap of a lateral circumflex femoral artery transverse branch in the treatment of ischemic necrosis of femoral head in young and middle-aged adults.Methods:From February 2017 to February 2019, 12 cases (15 hips) of young and middle-aged patients with avascular necrosis of femoral head were treated in the Department of Orthopaedic of Affiliated Zhongshan Hospital of Dalian University. The age of patients was 30-53 years old. According to Association Research Circulation Osseous (ARCO), 2 hips were graded in stage II b, 4 in ARCO II c, 1 in ARCO III a, 5 in ARCO III b, 2 in ARCO III c and 1 in ARCO IV. The greater trochanter bone flap with a lateral circumferential vascular branch was used to fill the necrotic area, and fixed by a biodegradable high purity magnesium screw in the bone flap transfer. At 3, 6 and 12 months postoperation, the patient came to the hospital outpatient clinic for follow-up, and then were reviewed once a year. Imaging efficacy was evaluated by comparing preoperative and postoperative imaging. The Harris score and Visual Anoalogue Scale (VAS) score were tested at 12 and 24 months after surgery. The Harris score and VAS score before and after surgery were compared by Friedman test, and P<0.05 was considered statistically significant. Results:All 12 patients (15 hips) were entered in the 24-36 months of follow-up. At 12 and 24 months after surgery, Harris score was found at 87 (86, 92) and 90 (87, 92) respertively, which were both higher than that before surgery [59 (52, 74)] with a significant statistical difference ( Z=-3.743, Z=-4.473, P<0.05). However, there was no significant difference in Harris scores between 12 and 24 months after the surgery ( Z=-0.730, P>0.05). At the 12 and 24 months after surgery, VAS score was found at 3 (2, 3) and 2 (1, 3) respertively, which were both lower than that before surgery [6 (5, 6) ] with a significant statistical difference ( Z=-3.560, Z=-4.656, P<0.05). There was no statistical difference in VAS scores between 12 and 24 months after surgery ( Z=-1.095, P>0.05). X-ray and CT scan showed that the bone flaps healed well and the areas of osteonecrosis were repaired. Thirteen femoral heads were in good shape, and 2 femoral heads had further collapse of hips. No patients underwent joint replacement surgery at the time of last follow-up. Conclusion:Fixation of the greater trochanter flap of lateral circumflex femoral artery transverse branch with a degradable high-purity magnesium screw can ensure the healing of the flap at the implantation site and avoid the displacement and shedding of the flap. It is a new therapeutic option to treat the avascular necrosis of femoral head of young and middle-aged people.

The internal organs and meridians were associated with Yin and Yang, five elements, six qi, and time and space, based on the holistic view of heaven, earth and human, according to Huangdi Neijing. The syndrome differentiation system of six meridians and Zang Fu meridians were established by Shanghan Zabing Lun, on the basis of the three Yin, three Yang, six meridians, and five Zang system in Huangdi Neijing. We put forward the concept of the six meridians syndrome differentiation system of circular motion, considering that the six meridians syndrome differentiation system actually implies the theory of circular motion. The syndrome differentiation system was constructed with the circular model of one qi circulating around the road, rising left and falling right, corresponding up and down, and maintaining conservation in the middle as the core, integrating Yin and Yang, five elements, six qi, Zang Fu and meridians, qi, blood and body fluid, and the integration of heaven, earth and human, focusing on "disease location and disease nature", taking classical prescriptions as the main treatments, and cooperating with external treatments such as acupuncture and moxibustion. We organically combined the circular motion with the syndrome differentiation of the six meridians, systematically interpreted the physiological bases, pathological changes, progressive patterns, and the treatments, based on syndrome differentiation, by inheriting the classical thinking mode of Hetu, Luoshu,Zhouyi, Huangdi Neijing, ShennongHerbal Classic, and Shanghan Zabing Lun.

Models of acute and chronic liver injury in mice were established using carbon tetrachloride (CCl4) and ethanol to explore the protective effects of Ganoderma lucidum spore glycopeptide on liver injury.Different dosage of Ganoderma lucidum spore glycopeptide (65,130,260 mg/kg) were given by gavage.The liver index and the levels of serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined.The contents of liver interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and inducible nitric oxide synthase (iNOS) were tested by enzyme-linked immunosorbent assay (ELISA).The pathological injury of liver tissue was observed by HE staining.The results showed that Ganoderma lucidum spore glycopeptide could significantly reduce the liver index and the contents of serum AST and ALT in mice of acute and chronic liver injury.In mice of chronic liver injury induced by CCl4, Ganoderma lucidum spore glycopeptide could significantly decrease the contents of liver IL-6, TNF-α and iNOS, and alleviate the pathological damage of liver tissue.Results suggested that Ganoderma lucidum spore glycopeptide might reduce acute and chronic liver injury with anti-inflammatory effects in mice.

Objective To evaluate the clinical efficacy of acupoint injection with BCG-polysaccharide nucleic acid (BCG-PSN) in treating bronchial asthma. Method Seventy-two patients with bronchial asthma were randomized into an acupoint injection group and a muscular injection group, 36 cases in each group. The acupoint injection group was intervened by acupoint injection with BCG-PSN to Zusanli (ST36) and Dingchuan (EX-B1) alternately, 1 mL for two points in total each time; the muscular injection group was intervened by muscular injection at the same dose and frequency, twice a week, for successive 3 months. The pulmonary function and asthma control test (ACT) were estimated before and after intervention and during March of the next year. Result After intervention, the FEV1 values were (80.97±2.31)% and (80.78±2.56)% respectively in the acupoint injection group and muscular injection group, and PEF values were (6.50±0.21)L/s and (6.48±0.25)L/s, and the between-group differences were statistically insignificant (P>0.05). The ACT score was (23.02±1.03) in the acupoint injection group, significantly better than (22.40±2.04) in the muscular injection group (P<0.05). The follow-up study showed that the ACT score in the acupoint injection group was superior to that in the muscular injection group (P<0.05). Conclusion Acupoint injection and muscular injection with BCG-PSN can equally improve the pulmonary function in bronchial asthma, while the acupoint injection can produce a more significant effect than muscular injection in improving ACT.

This study was designed to investigate inhibitory effects and possible mechanisms of snake venom tripeptide (pENW) on platelet adhesion in order to promote the development of a novel anti-platelet therapy. To study the inhibitory effects of pENW on platelet adhesion, washed platelets pre-incubated with pENW (116.5-466.2 μmol x L(-1)) were used to test the ability of platelet adhesion to fibrinogen. Effect of pENW on fibrin clot retraction was also tested. Effect of pENW on platelets viability was tested by MTT assay. Effect of pENW on reactive-oxygen species (ROS) levels of platelet was studied by flow cytometry assay. Calcium mobilization in Fura-2/AM-loaded platelets was monitored with a spectrofluorimeter. Cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), thromboxane A2 (determined as its metabolite thromboxane B2) were measured using enzyme immunoassay kits. Akt, ERK and p38 phosphorylation were tested by Western blot. The results showed that pENW inhibited platelet adhesion and fibrin clot retraction in a concentration-dependent manner without cytotoxicity. Intracellular cGMP and cAMP in both resting and thrombin-activated platelets were increased by pENW. In addition, pENW attenuated intracellular Ca2+ mobilization and TXA2 production in platelets stimulated by thrombin. As shown by Western blot assay, Akt, ERK and p38 phosphorylation in thrombin-induced platelet were attenuated by pENW. However, inhibitory effects of pENW had nothing to do with ROS. Thus, pENW exhibited a significant inhibition on platelet adhesion to fibrinogen, which means pENW could block the first step of thrombosis as while as retard the more stable clot formation. The mechanisms of pENW on inhibition platelet adhesion might be related to instant regulations, such as protein kinases.

Objective To establish a stable animal model for sequentially dynamic and direct monitoring of the skin wound infection. Methods The mice with full-thickness skin incisions were replicated. After immediate subcutaneous suture,the mice were randomly divided into four groups,ie,Group A was inoculated with 50 μl sterile PBS solution),Groups B,C and D were inoculated with 50 μl suspension containing 1 × 106,1 × 108 and 1 × 1010 colony forming unit (CFU)/ml bioluminescent methicillin-resistant staphylococcus aureus (MRSA) respectively.Then,the diet behavior of each group was observed and the mean weight and mortality of each group were also recorded at different time points.The bioluminescent intensity of fluoresce in the wounds was recorded at different time points by using the charge-coupled device (CCD) based imaging system.Local wound tissues were incised at 24 hours after inoculation for HE staining so as to observe wound inflammatory reaction in each group.Wound healing time of each group was also recorded. Results ( 1 ) Average weight:Groups A and B showed unobvious changes in weight; Group C lightened until day 3 after inoculation and then recovered gradually to the preinoculation level at day 14; Group D lightened gradually until death.(2)Mortality:Groups A and B had no death; Group C had 10％ deaths at day 14; Group D had 100％ deaths.(3) Bioluminescent intensity of wounds:Groups A and B showed a gradual weakened luminescence since the day of inoculation and had almost complete disappearance at days 5 and 7 respectively; there was no sign of obvious increase or decrease in Group C from the day of inoculation till day 14 ; Group D had a gradual increase since the day of inoculation and the luminous area expanded until the death.(4) HE staining at 24 hours after inoculation:all the four groups showed inflammatory cell infiltration,especially in Groups C and D.(5) Wound healing time:wound healed at days 5 and 7 after inoculation in Groups A and B; the wounds showed no healing even at day 14 in the Group C,but the wounds length and area did not show obvious enlargement or diminishment ; the wounds extended gradually until the death in the Group D,since the day of inoculation. Conclusions The inoculation of 50 μl suspension with 1 × 108 CFU/ml bioluminescent MRSA to full-thickness skin incision rats allows direct,real-time dynamic and continuous detection of the occurrence and development of the wound infections.The infection model is easy to make and has stability and high repeatability.

ObjectiveTo develop a new sutureless technique (photochemical tissue bonding,PTB ) for repair of corneal perforation. Methods A total of 60 rabbits were used for creating corneal perforation models.The corneal perforation on the left eye was repaired by sutures and the injury on the right eye was fixed with the use of amniotic membrane with PTB.The outcomes of the two mentioned repair methods were compared by observing the leakage of aqueous and the morphology of the anterior chamber at different instants,measuring the intraocular pressure (IOP) and observing the formation of neo-vessels and scars of cornea in the use of histological analysis. Results There was no leakage of aqueous and no difference for morphology evaluation in both treatments.PTB could adhere AM on the cornea to restore the corneal perforation.The peak IOP in the PTB treatment group at days 0,7 and 14 postoperative [ (531.2 ±49.5) mm Hg,(542.6 ±74.8) mm Hg and (603.9 ±69.1) mm Hg,respectively] was significantly higher than that in the suture group at the same instants [ (41.3 ±12.7) mm Hg,(142.6 ±25.4) mm Hg and (333.3 ± 66.7) mm Hg,respectively] (P ＜0.O1 ).Compared with suture repair,the treatment with PTB resulted in a better outcome of wound healing with less neo-vessels and less scars of cornea. Conclusion PTB treatment for repair of corneal perforation is superior to suture repair.

Objective To study the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on the expression of vascular endotllelial growth factor (VEGF) in human dermal fibroblast. Methods In vitro human dermal fibroblasts in good status were incubated with GM-CSF (GM-CSF group) or non-GM-CSF (control group) culture medium for different periods of time. The mRNA, protein expression of VEGF in derma fibroblast were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively, and the secretion of VEGF in supernatant was measured by enzyme linked immunosorbant assay (ELISA). Results The expression of VEGF mRNA from dermal fibroblasts was increased significantly after l or more hours of incubation with GM-CSF comparing with the control (P＜0.05). 6 hours of stimulation by GM-CSF caused maximal expression of VEGF mRNA. The expression of VEGF protein in dermal fibroblasts was increased from 12 hours and was peaked at 24 hour after stimulation by GM-CSF. VEGF protein from the supernatant of the dermal fibroblasts was also raised persistently from 12 hour after stimulation by GM-CSF and was improved remarkably compared with the control. Conclusions GM-CSF can up-regulate directly the expression of VEGF in human derma fibroblast, which may be one of the mechanisms that GM-CSF accelerates neovascularization in wound healing.

ObjectiveTo observe production of vascular endothelial growth factor (VEGF) induced by granulocyte/macrophage colony-stimulating factor (GMCSF)via ERK nerve growth factor (NF)-κB singling pathway in human fibroblasts during wound healing and explore relating mechanism.MethodsHuman fibroblasts from the injured skin were used for this study and treated with GMCSF.RT-PCR was used for analyzing the protein and mRNA levels of VEGF and Western blotting was employed to determine the phosphorylation of ERK. The fibroblasts were pre-treated with ERK specific inhibitor PD98059 and further treated with GMCSF, then the fibroblasts and the supernatant were collected for detection of protein level of VEGF by means of Western blot. ERK signal pathway was inhibited to detect the activation of NF-κB by means of immunofluorescence staining. Furthermore, the nuclear and cytoplasmic extraction kit was used to separate the cytoplasm and nucleus and Western blot employed for observation of the NF-κB activation. ResultsThe mRNA level and protein level of VEGF were increased significantly with treatment with higher concentration of GMCSF in a dose-dependent manner. VEGF mRNA level was increased two hours after administration with GMCSF and reached peak at 4-6 hours. GMCSF could remarkably activate the ERK phosphorylation. Compared with GMCSF, the ERK specific inhibitor PD98059inhibited significantly the effect of GMCSF in inducing VEGF expression (P ＜ 0.05). Western blot and immunofluorescence staining analyses showed that the activation of NF-ΚB was inhibited with reduced production of VEGF after GMCSF treatment.Conclusion GMCSF up-regulates production of VEGF through activating NF-κB via ERK signal pathway in the human fibroblasts.