Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.

OBJECTIVE: To investigate the influence of posterior osteotomy on spinopelvic parameters in lumbar degenerative kyphosis (LDK) patients. METHODS: The clinical data of 21 patients with lumbar degenerative kyphosis who underwent osteotomy from January 2012 to December 2015 were retrospectively analyzed. There were 5 males and 16 females, aged from 55 to 76 years with an average of (66.24±5.13) years. All patients had taken preoperative and postoperative full length spinal X-ray, analyzing the spinopelvic parameters as thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). RESULTS: All operations were successful, the average operative time was 190 min (160 to 220 min) and intraoperative blood loss was 1 000 ml (800 to 1900 ml). Parameters of the patients between preoperative and period 1-year follow-up were as follows : preoperative TK increased from (31.67±21.13) ° to (34.67±11.60) °, LL corrected from (4.76±3.17) ° to (37.41±6.28) °, PT reduced from (33.94±5.01) ° to (20.12±5.36) °, and SS improved from (18.47±2.60) ° to (31.71±4.30) °, SVA restored from (13.24±3.60) cm to (2.82±1.33) cm. There were significant differences of spinopelvic parameters between preoperation and postoperation (<0.05). CONCLUSION Posterior osteotomy can effectively reconstruct the sagittal balance of spinopelvis in patients with lumbar degenerative kyphosis. The recovery of lumbar lordosis and sacral slope is closely related to the reconstruction of sagittal balance.

Objective To explore the efficacy of renal transplantation plus hematopoietic stem cell transplantation on inducing immune tolerance and summarize its long-term follow-up outcomes . Methods From 2009 to 2018 ,a total of 11 cases of living related donor kidney transplantation plus hematopoietic stem cell transplantation were performed .Two of them were HLA-matched and the remainder were mismatched for one HLA haplotype . The donor hematopoietic stem cells were mobilized using granulocyte colony-stimulating factor at 5 days pre-transplantation and collected at 1 day pre-operation .The recipients received total lymphoid irradiation for 3 days pre-transplantation and received anti-thymocyte globulin induction during transplantation .The donor hematopoietic stem cells were infused at 2 ,4 and 6 postoperative day .Postoperative regulatory T cells ,chimerism ,B cell activating factor and mixed lymphocyte culture and other parameters were detected and long-term follow-up outcomes tracked .Results The immune tolerance-inducible recipients had a significant increase in activated Treg .One HLA-matched recipient achieved 30％-50％ of chimerism and lost after 6 months .However ,other recipients did not achieve mixed chimerism .The BAFF of recipient spiked sharply after transplantation .Mixed lymphocyte culture indicated that a donor-specific low response was induced .The recipients were followed up for 717 to 3612 days .The first recipient lost renal function and another ten recipients had stable renal function . None of the recipients had myelosuppression or graft-versus-host disease .Allograft biopsy confirmed only one case of mild acute rejection . The dose of immunosuppressive agents was lowered in 5 patients .Conclusions Hematopoietic stem cell transplantation for inducing tolerance is safe during renal transplantation . And chimerism is essential for inducing immune tolerance .

To explore serum levels of miR‐21 and miR‐155 in patients with T2DM complicated CHD and their relationship with lipid metabolism .Methods : A total of 134 T2DM patients treated in our hospital from 2016 to 2017 , were divided into T2DM + CHD group (n＝60) and pure T2DM group (n＝74).Blood glucose and blood lipid levels and serum miR‐21 and miR‐155 levels were measured and were compared between two groups .Results :There were no significant difference in general data , blood pressure , body mass index (BMI) , glycosylated hemo‐globin A1c (HbA1c) , plasma glucose and total cholesterol (TC) between two groups , P＞0. 05 all.Compared with pure T2DM group , there were significant rise in levels of triglyceride (TG) [ (1. 89 ± 0.92) mmol／L vs.(2. 75 ± 1.61) mmol／L] , LDL‐C [ (2.83 ± 0.79) mmol／L vs.(3. 52 ± 1.24) mmol／L] and serum miR‐21 [ (0. 93 ± 0. 15) vs.(1. 86 ± 0.24 )] , and significant reductions in levels of HDL‐C [ (1.35 ± 0. 34 ) mmol／L vs.(0. 94 ± 0.31 ) mmol／L] and serum miR‐155 [ (0. 95 ± 0.19) vs.(0. 27 ± 0. 10)] in T2DM + CHD group , P＝0.001 all.Multiva‐riate Logistic regression analysis indicated that TG , LDL‐C and miR‐21 were independent risk factors for T2DM +CHD (OR＝2. 800～4. 986 , P＜0.05 all) , while HDL‐C and miR‐155 were its independent protective factors (OR＝0.314 , 0.327 , P＜ 0.05 both).Pearson correlation analysis indicated that serum miR‐21 level was significant positively correlated with TG and LDL‐C levels ( r＝0. 415 , 0.506 , P＜0.05 or ＜0. 01) , and serum miR‐155 level was significant inversely correlated with TG and LDL‐C levels ( r＝ －0. 397 ,－0. 526 , P＜0.05 or ＜0. 01 ).Con‐clusion : Serum miR‐21 level was significant positively correlated with TG and LDL‐C levels , but serum miR‐155 level was significant inversely correlated with TG and LDL‐C levels ,

OBJECTIVE: To investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance. METHODS: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry (FCM). The expression level of IL-10,TGF-β, CD40 and CD40L was detected by AimPlex Flow High Throughput Screening Technology. RESULTS: The of Breg cells in ITP patients was significantly lower than that in normal controls (P<0.05)，the expression levels of IL-10,TGF-β and CD40L in ITP patients were also significantly lower than those in normal controls (P<0.05). The contents of Th1 cells in ITP patients were significantly higher than that in normal controls (P<0.05), whereas the contents of Th2, Th17 and Treg cells in ITP patients were significantly lower than those in normal controls (P<0.05). CONCLUSION The Breg cells may play an important role in the pathogenesis of ITP.
B-Lymphocytes, Regulatory ; Humans ; T-Lymphocytes, Regulatory ; Th17 Cells ; Thrombocytopenia

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 10/L to 1.08 ± 0.62 × 10/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 μ g/L (P<0.05), 3 months with 33.56 ± 15.28 μ g/L (P<0.05), and 6 months with 36.78 ± 11.92 μ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 μ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, μ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, μ g/L, P<0.05). CONCLUSION QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.

Background: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). Methods: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. Results: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ² = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ² = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. Conclusion Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

BACKGROUND: Percutaneous kyphoplasty is an effective treatment method for senile degenerative thoracic osteoporotic vertebral compression fractures. However, its clinical long-term effect is controversial among scholars both inside and outside China. The poly(methyl methacrylate) (PMMA) bone cement commonly used in percutaneous kyphoplasty has good plasticity and formability, but its biocompatibility is not yet clear. Injectable artificial bone is a novel filling material to induce bone formation, but its long-term efficacy remains to be verified. OBJECTIVE: To compare the efficacy of OSTEOPAL?Plus PMMA bone cement and GeneX? injectable artificial bone graft in the treatment of senile degenerative thoracic osteoporotic vertebral compression fractures at 24 months postoperatively. METHODS: This is a prospective, single-center, open-label, randomized controlled clinical trial. A total of 378 patients with senile degenerative thoracic osteoporotic vertebral compression fractures will be recruited from the Department of Orthopedics, Affiliated Hospital of Qinghai University, China. The patients will be randomized into two groups and undergo percutaneous kyphoplasty. The PMMA group (n=189) will be treated with OSTEOPAL?Plus PMMA bone cement. The artificial bone group (n=189) will be treated with GeneX? injectable artificial bone. Follow-ups will be conducted at 1 week and at 3, 6, 12, and 24 months. The primary outcome measure will be the vertebral body height restoration rate at 24 months postoperatively to evaluate the repair effect of the damaged thoracic vertebra. The secondary outcome measures will be the vertebral body height restoration rate at 1 week and 3, 6, and 12 months postoperatively; the incidence of bone cement leakage at 1 week and 3, 6, 12, and 24 months postoperatively; the visual analog scale score, Oswestry Disability Index, compression rate of the anterior vertebral height, and thoracic morphology revealed by computed tomography preoperatively and at 1 week and 3, 6, 12, and 24 months postoperatively; and the incidence of adverse reactions at 1 week and 3, 6, 12, and 24 months postoperatively. DISCUSSION: Our results will verify whether OSTEOPAL?Plus PMMA bone cement and GeneX? injectable artificial bone graft are effective and safe for treating senile degenerative thoracic osteoporotic vertebral compression fractures in the short-term and at the 2-year follow-up. This study was approved by the Medical Ethics Committee of Affiliated Hospital of Qinghai University of China in November 2017 (approval number: 2017-11). The study protocol will be conducted in accordance with the Declaration of Helsinki, formulated by the World Medical Association. Written informed consent will be obtained from all participants who will be fully informed of study protocol and process. This trial was designed in December 2017. The recruitment of subjects and data collection will begin in July 2018. Outcome measures will be analyzed in September 2020. This trial will be completed in October 2020. The results of the trial will be reported in a scientific conference or disseminated in a peer-reviewed journal. This trial had been registered in the Chinese Clinical Trial Registry (registration No:ChiCTR1800015411). The version of this study protocol is 1.0.

Objective To observe the effect of breathing training on postpartum stress urinary incontinence (SUI) based on pelvic floor muscle exercise and biofeedback electrical stimulation. Methods From July to October, 2017, 64 SUI patients at the sixth week after childbirth were randomly divided into con-trol group (n=32) and observation group (n=32). The control group was treated with pelvic floor muscle exercise and biofeedback electrical stimulation. The observation group was supplemented with breathing training addition-ally. The pelvic floor muscle myoelectric value, urinary incontinence frequency, one hour urine pad test and the average thickness of the transversus abdominis were evaluated before and twelve weeks after treatment. Results Before treatment, there was no significant difference in the pelvic floor muscle myoelectric value, urinary incon-tinence frequency, one hour urine pad test and the average thickness of the transversus abdominis between two groups (P>0.05). Twelve weeks after treatment, the pelvic floor muscle myoelectric value significantly increased in both groups (t>12.564, P<0.001), and was higher in the observation group than in the control group (t=14.064, P<0.001); the urinary incontinence frequency and the positive rate of one hour urine pad test significantly de-creased in both groups (Z>9.615, P<0.001), and were lower in the observation group than in the control group (Z=-2.767, χ2=6.564, P<0.05); the average thickness of the transversus abdominis had no improvement in the control group (t=-1.510, P>0.05), and significantly increased in the observation group (t=-10.681, P<0.01), which was higher in the observation group than in the control group (t=7.541, P<0.001). Conclusion On the basis of pelvic floor muscle exercise and biofeedback electrical stimulation, supplementation with breathing training could reduce the symptoms of postpartum stress urinary incontinence, and improve the func-tion and the quality of life.

OBJECTIVETo analyze the imbalance of pro-inflammatory and anti-inflammatory cytokines in the patients of immune thrombocytopenia (ITP).

METHODSThirty-five patients with ITP were enrolled in ITP group, while 28 healthy persons were included in control group. The expressions of IL-8, IL-17A, IL-22, TNF-α, IFN-γ, IL-4, CD40, CD40L, TGF-β and IL-10 were detected by flow cytometry with aimPlex multiple immunoassay Flow.

RESULTSThe expressions of pro-inflammatory factors IL-8, IL-17A, IL-22, IFN-γ and TNF-α in ITP group all were significantly higher than that in the control group (P<0.05), however the expressions of anti-inflammatory factors IL-4, CD40L, TGF-β and IL-10 in ITP group all were significantly lower than that in the control group (P<0.05). The expression of CD40 was not significantly different between ITP group and control group (P>0.05). Expressions of TNF-α significantly related with platelet counts in both ITP group and control group (ITP group, r=0.64, P<0.05; control group, r=-0.41, P<0.05). However the expression of CD40, TGF-β, CD40L, IL-8, IL-17A, IL-22, IL-10, IL-1β, IFN-γ and IL-4 significantly did not relate with platelet counts in both ITP and control group.

CONCLUSIONSThe secretory imbalance between pro-inflammatory and anti-inflammatory cytokines exists in the patients of ITP. The decrease of Plt regulated may be regulated by the abnormal expression of TNF-α.