Objective To investigate the effect of diet-induced obesity on ischemia brain injury in mice.Methods A total of 60 male C57/Bl6 mice were treated with high-fat (high-fat group, n=30) or normal diet (control group, n=30) for three months, and each group was further divided into sham group and model group, with 15 mice in each subgroup. The model group was established the middle cerebral artery occlusion model. The nerve injury was evaluated with Neurologic Severity Score (NSS), the infarct volume was evaluated by 2,3,5- chlorinated three phenyl tetrazolium chloride (TTC) staining, the expression of sirtuin (Sirt1), Wnt and apoptosis inducing factor (AIF) were detected with Western blotting seven days after modeling.Results Seven days after modeling, the NSS was higher in the high-fat group than in the control group (t=10.053, P<; 0.05), and no significant difference was found in the infarct volume between two groups (t=6.872, P>; 0.05). The expression of Sirt1 (t=8.462, P<; 0.05) and AIF (t=8.471, P<; 0.05) was higher, and the expression of Wnt (t=17.752, P<; 0.01) was lower in the high-fat group than in the control group.Conclusion Obesity could affect the recovery of mice with MCAO, which may related with impaired Wnt signaling.

Objective: To explore the effect of high mobility group box-1 protein (HMGB1) on the balance of Th17/Treg in patients with immune thrombocytopenia (ITP). Methods: A total of 30 patients who were first diagnosed as ITP in the Fifth People's Hospital of Datong from July 2017 to April 2018 were selected as the case group, and another 30 healthy volunteers in the corresponding period were taken as the control group. The proportion of Th17 and Treg cells was detected by using flow cytometry, and the concentration of HMGB1, interleukin (IL)-17 and transforming growth factor β (TGF-β) in plasma was tested by using enzyme-linked immunosorbent assay (ELISA). Isolated peripheral blood mononuclear cells (PBMC) were cultured in vitro. After the treatment with recombinant human HMGB1 (rhHMGB1), real-time polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression changes in Treg cell transcription factor intracellular forkhead helix transcription factor 3 (Foxp3) and Th17 cell transcription factor retinoid related orphan receptor γt (RORγt). The differences of indicators in Treg cell transcription factor peripheral blood between the case group and the control group were compared, and the balance correlation between HMGB1 and Th17/Treg was analyzed. Results: Compared with the healthy control group, the proportion of Th17 cells and the expression level of HMGB1 and IL-17 in peripheral blood of ITP patients were increased (all P < 0.01), while the proportion of Treg cells and the level of TGF-β were decreased (all P < 0.01). The proportion of Th17 cells and the expression level of IL-17 and HMGB1 in peripheral blood of ITP patients were positively correlated with the concentration of HMGB1 (all P < 0.01); the proportion of Treg cells and the level of TGF-β were negatively correlated with the expression level of HMGB1 (all P < 0.01). In vitro experiments, the expression of intracellular RORγt mRNA was increased compared with the negative control group (1.50±0.24 vs. 0.93±0.22, t = 9.612, P < 0.01), and the expression of Foxp3 mRNA was decreased compared with the negative control group after the stimulation of PBMC by rhHMGB1 (0.72±0.19 vs. 1.08±0.18, t = 7.387, P < 0.01). Conclusion The high level of HMGB1 in the peripheral blood of ITP patients induces Th17/Treg imbalance and aggravates inflammatory reactions, which may be an important cause of ITP.

Purpose:To study the efficacy and safety of docetaxel administrated weekly plus cisplatin in the treatment for patients with advanced non-small-cell lung cancer (NSCLC). Methods:Thirty-six patients with stage ⅢB,stage Ⅳ not treated previously by chemotherapy,or recurrenct after operation NSCLC received intravenous infusions of docetaxel at 35mg/m 2 three consecutive weeks,followed by a week of rest;and intravenous infusions of cisplatin at 75 mg/m 2 every four weeks. Results:There were 12 partial responses for an objective response rate of 33 %. The median survival was 11.5 months (range 4-27 months),and the 1-year survival was 50%. Hematologic toxicities,which were mild,included grade Ⅲ/Ⅳ neutropenia in 22%. The common nonhematologic toxicities included grade 2-3 nausea and vomiting (39%) and grade 2-3 asthenia (36%). Conclusions:Consecutive weekly administrations of docetaxel for 3 weeks plus cisplatin produce minimal myelosuppression and shows activity in the treatment of patients without previous chemtherapy with advanced NSCLC.

ObjectiveTo investigate the efficacy of interactive thumbtack needle embedding plus rehabilitation instruction in treating knee osteoarthritis.Method Seventy outpatients with knee osteoarthritis were randomly allocated to acupuncture-rehabilitation and control groups, 35 cases each. The control group received rehabilitation instruction alone and the treatment group, interactive thumbtack needle embedding in addition. The function of the affected knee was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and manual muscle test (MMT) in the two groups of patients before and after two courses of treatment. The therapeutic effect was evaluated using Nimodipine method accordingto 2002Guidelines on Clinical Study of New Chinese Herbal Medicine(trial).ResultAfter two courses of treatment, there were a statistically significant pre-/post-treatment differences in the WOMAC total score, pain score, stiffness score and function score in both groups (P<0.01). There were also statistically significant post-treatment differences between the two groups (P<0.05). There were statistically significant pre-/post-treatment differences in quadriceps femoris and hamstring muscles MMT in both groups of patients (P<0.01) but there were no statistically significant differences in the same items between the two groups (P>0.05). There was a statistically significant difference in therapeutic effect between the two groups (P<0.05).ConclusionInteractive thumbtack needle embedding plus rehabilitation instruction has a definite therapeutic effect on knee osteoarthritis.

Objective To evaluate the effectiveness of uterine arterial embolization (UAE) in the management of uterine fibroids (UF) and adenomyoma. Methods The UAE was carried out in 22 cases of UF and 2 cases of adenomyoma, including bilateral UAE in 23 cases and unilateral UAE in 1 case, by using polyvinyl alcohol (PVA) particles as embolic materials. Results The success rate of UAE in the study was 95 8% (23/24). No serious complications occurred. The uterine and UF volume decreased remarkably in size 6 months after the treatment ( t =2 391 and 3 990, respectively; P =0 022 and 0.000, respectively). In the patient who underwent unilateral UAE, the UF gradually increased in size and a hysterectomy was required. The 2 patients with adenomyoma experienced relief with this treatment but had a recurrence 4 months after the surgery. Conclusions UAE is a safe and effective method in the management of UF but its long-term effects remains a question to be answered through further observations . The efficacy of treatment of this method for adenomyoma is not apparent.

Objective: To investigate the application value of hs-CRP and BNP detection in COPD patients with pulmonary heart disease. Methods: From January 2016 to January 2018, 80 patients with COPD in the Fifth People's Hospital of Datong were selected.Forty-two COPD patients complicated with pulmonary heart disease were selected as COPD and cor pulmonale group, 38 COPD patients without pulmonary heart disease were selected as COPD group, and 30 healthy volunteers were selected as control group.The differences of hs-CRP and BNP levels were compared, and the diagnostic value of hs-CRP and BNP for COPD combined with pulmonary heart disease was analyzed. Results: There were statistically significant differences in hs-CRP[(72.5±20.4) mg/L vs.(37.5±9.8) mg/L vs.(3.7±1.2)mg/L], BNP[(362.8±86.9) ng/L vs.(125.9±34.8) ng/L vs.(28.5±9.9)ng/L] among the COPD and cor pulmonale group, COPD group and control group (F=9.245, 14.668, all P<0.05). The hs-CRP and BNP levels in the COPD and cor pulmonale group were significantly higher than those in the other two groups(t=19.294, 11.576, 21.385, 9.258, 9.258, all P<0.05), which of the COPD group were significantly higher than those of the control group (t=8.912, 12.567, all P<0.05). The best boundary value of BNP in diagnosis of COPD with cor pulmonale was 261.8ng/L, and its diagnostic sensitivity and specificity were 96.2% and 85.4%, respectively, the area under the line was 0.834, which were all higher than those of hs-CRP.With the increase of cardiac function, the levels of hs-CRP[(38.5±10.3) mg/L vs.(51.4±14.8) mg/L vs.(75.1±21.5) mg/L vs.(93.7±31.8)mg/L], BNP[(142.8±56.5) ng/L vs.(285.9±94.8) ng/L vs.(352.5±118.2) ng/L vs.(478.5±130.3)ng/L] increased, the differences were statistically significant (F=13.577, 16.776, all P<0.05). There were significant correlation between hs-CRP, BNP levels and COPD patients complicated with cor pulmonale (r=0.675, 0.766, all P<0.05). Conclusion hs-CRP and BNP have high diagnostic potency for COPD patients combined with cor pulmonale, and are positively correlated with cardiac function classification.

【Objective】 To explore the effect and mechanism of Fasudil in the treatment of experimental autoimmune myocarditis (EAM) in mice so as to provide a theoretical basis for the clinical use of Fasudil in treating myocarditis. 【Methods】 Balb/c male mice were used as the research objects, and the EAM mice model was constructed using MyHC-α614-629 polypeptide. Mononuclear cells were isolated and cultured to detect the number of mononuclear cells in mouse spleen. Inflammation infiltration, fibrosis and IL-6 expression in mouse myocardial tissue were detected by HE staining, Masson staining and immunohistochemistry, respectively. The protein expressions of Notch1 and IL-6 were detected by Western blotting. qRT-PCR was used to detect the expressions of pro-inflammatory factors (IL-1α, IL-1β and IL-6) as well as key genes of TLRs and NOTCH signaling pathway. 【Results】 EAM mice showed increased HW, decreased BW, increased HW/e-BW, and increased inflammatory infiltration and fibrosis in myocardial tissue. The above-mentioned symptoms or pathological features were improved in EAM mice treated with Fasudil. The analysis showed that the pro-inflammatory factors IL-1α, IL-1β and IL-6 in the myocardial tissue of EAM mice were significantly increased, but only the expression of IL-6 was statistically different after Fasudil treatment compared with the control group. In addition, TLRs signaling pathway might also play an important role in the EAM mice treated with Fasudil. The expressions of IL-6 and Notch1 were consistent, and the expressions of the key genes of NOTCH signaling pathway (Notch1, Hes1 and Jag2) were down-regulated after Fasudil treatment. 【Conclusion】 Fasudil exerts a protective effect on down-regulation of IL-6 expression by inhibiting the NOTCH signaling pathway in EAM mice.

Objective: To study the clinical effect of fasudil plus cattle encephalon glycoside and ignotin injection in treating diabetic deafness and tinnitus. Methods: From January 2016 to December 2016, 60 patients with diabetic deafness and tinnitus in the Fifth People's Hospital of Datong were selected and randomly divided into two groups according to the digital table, with 30 cases in each group.The treatment group received fasudil injection plus cattle encephalon glycoside and ignotin injection (iv gtt), and the control group received cattle encephalon glycoside and ignotin injection.The effective rate after treatment for 10 days and 20 days were compared between the two groups. Results: Compared with the control group, the effective rate of hearing in the treatment group was not higher at 10 days after treatment (26.7% vs.16.7%, χ²=0.884, P=0.347), while it was higher in the treatment group at 20 days after treatment (53.3% vs.26.7%, χ²=4.444, P=0.035). The effective rate of tinnitus in the treatment group at 10 days after treatment was not higher compared with the control group (30.0% vs.20.0%, χ²=1.491, P=0.222), while it was higher in the treatment group at 20 days after treatment (56.7% vs.30.0%, χ²=4.344, P=0.037). As far as hearing threshold: there were no statistically significant differences between the control group and the observation group before treatment and 10 days after treatment(all P>0.05). The hearing threshold of the observation group was significantly better than that of the control group at 20 days after treatment (t=-2.511, P=0.02). Conclusion The combination therapy of fasudil injection plus cattle encephalon glycoside and ignotin injection has better efficacy for diabetic deafness and tinnitus.

OBJECTIVE: To explore the therapeutic effect of Fasudil-modified splenic mononuclear cells (MNCs) in experimental autoimmune encephalomyelitis (EAE) and the possible mechanisms.
 METHODS: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to establish active immunity EAE model. Splenic MNCs were isolated on the 9th day after immunization and treated with or without Fasudil for 72 h in vitro. These cells were collected for analysis of the variance of T cell subtypes, the level of cytokines and the activity of Rho kinase (ROCK). MNCs (5×107 cells) were resuspended in 500 µL of phosphate buffer solution (PBS) and transferred into EAE model (intraperitoneal injection), which was divided into a PBS-MNCs group and a Fasudil-MNCs group. Changes of body weight and clinical symptom scores were observed.
 RESULTS: Splenic encephalitogenic MNCs from EAE mice on the 9th day after immunization could establish passive transfer EAE model. But Fasudil-treated MNCs did not trigger EAE development. Compared with the PBS-MNCs group, the loss of body weight was less in the Fasudil-MNCs group. The in vitro experiment indicated that Fasudil could suppress the activity of ROCK on MNCs (P<0.01), decrease the percentage of CD4+ T cells with the expression of interferon-γ (IFN-γ) and interleukin-17 (IL-17) (IFN-γ: P<0.01; IL-17: P<0.05), while increase the secretion of CD4+ T cells with the expression of transforming growth factor-β (TGF-β) and IL-10 (all P<0.001) . Furthermore, Fasudil could inhibit the release of IL-17 (P<0.001) and enhance the level of IL-10 (P<0.05).
 CONCLUSION Fasudil-modified cell therapy affects the occurrence and development of EAE by inhibiting the inflammatory reaction of helper T cell 1 (Th1) and Th17 while enhancing the immunoregulative effect of Th2.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; Animals ; Encephalomyelitis, Autoimmune, Experimental ; Female ; Interferon-gamma ; Interleukin-10 ; Interleukin-17 ; Mice ; Mice, Inbred C57BL ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; T-Lymphocytes ; Transforming Growth Factor beta ; rho-Associated Kinases

OBJECTIVE To investigate the improvement effect and mechanism of triptolide （TP） on sciatica rats. METHODS Sciatica rat model was prepared and then randomly divided into model group （normal saline）， indomethacin group （positive control， 7.5 mg/kg）， TP low-dose and high-dose groups （TP-L group and TP-H group， 50， 100 μg/kg TP）， and high-dose TP+ stimulator of interferon gene （STING） activator group （TP-H+DMXAA group， 100 μg/kg TP+25 mg/kg DMXAA）， with 12 rats in each group. Another 12 unligated rats were selected as sham operation group （normal saline）. After 14 days of intraperitoneal administration， the paw mechanical withdrawal threshold （PWT） and paw withdrawal thermal latency （PWL） were detected； the pathological changes， morphology of sciatic nerve and the number of microglia in sciatic nerve were observed. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， mRNA and protein expression levels of cyclic guanosine monophosphate- adenosine monophosphate synthase （cGAS） and STING in sciatic nerve were detected. RESULTS Compared with sham operation group， PWT and PWL of rats in model group were obviously reduced and shortened， the number of Nissl bodies was obviously decreased， while the number of microglia， sciatic neuropathology score， the levels of IL-1β and TNF-α， mRNA and protein expressions of cGAS and STING were obviously increased （P＜0.05）， and sciatic nerve injury was serious. Compared with model group， the changes of various indexes in indomethacin group， TP-L group and TP-H group were opposite to the above （P＜0.05）， and sciatic nerve injury was reduced. STING activator DMXAA weakened the inhibitory effect of TP on the activity of microglia and inflammatory response in sciatica rats （P＜0.05）. CONCLUSIONS TP may reduce the activity of microglia and inflammatory response by down-regulating the cGAS/STING signaling pathway， thus alleviating sciatica in rats.