Proceedings of 2018 Asia Pacific Medicine and Bio-Immunology Association (APAMBI) A randomized double-blind controlled clinical trial to evaluate the efficacy of recombinant human tumor necrosis factor-α receptor Ⅱ fusion protein in juvenile idiopathic arthritis Study on the expression level of myeloid source suppressor cells in juvenile idiopathic arthritis and the mechanism of the effect on the differentiation of TH17 cells

Objective: Research the Recombinant Human Tumor Necrosis Factor-α Receptor type- Ⅱ fusion protein antibody (Etanercept) for Treatment of juvenile idiopathic arthritis (JIA). A randomized double-blind controlled clinical trial was conducted, to provide evidence to better use of this drug in clinical application. Methods: Randomized double-blind principle was applied to divide the 124 JIA cases into control and treatment group. Slow-acting antirheumatic, nonsteroidal drugs or adrenocortical hormone were applied in these cases as basic drugs. There are no significant differences (P > 0.05) of clinical classification and basic treatment between the two groups. 62 cases of treatment group achieved subcutaneous Etanercept, 0.8mg/kg per week with a six mouth’s period of treatment. The group included 17 oligoarticular cases (27.4 2%), 15 polyarticular cases (24.19%) and 30 SO-JIA cases (48.38%). The ACR Ped - 30, 50,70 were used to assess the clinical efficacy. The occurrence of adverse reactions is monitored and recorded at the same time. Results: The remission rate of different cases in treatment group was different at each time point (P < 0.05). The clinical remission rate of SO-JIA cases was lower compared with the two other types (P <0.05). The SO-JIA cases achieved 44% ACR Pedi50 remission after 3 months’ treatment, and after 6 months’ treatment they received 40.7% ACR Pedi50 remission and 29.6%ACR Pedi70 remission. The oligoarticular cases and polyarticular cases didn’t have obvious difference in ACR Pedi30, 50, 70 remission rates at different time. 80% of these cases had ACR Pedi50 remission after 6 months’ treatment and above 50% had ACR Pedi70 remission. These were significantly different (P <0.05) compared with the control group. In the SO-JIA treatment group, Etanercept was effective in 3 SOJIA-MAS cases that conventional treatment didn’t help, and this did not conform to the report in the literature. 2 So - JIA cases merged with muscular stiffness after 1-week treatment. 5 So-JIA cases had upper respiratory tract infection, diarrhoea and other infection for several times during the treatment, one of them had chickenpox infection. They all got remission after drug withdrawal and symptomatic treatment. The adverse reactions of SO-JIA subgroups were 23.3%, while the other 2 types had no adverse reaction. Conclusion: Etanercept has a good therapeutic effect for JIA cases that mainly have articular lesions such as the oligoarticular type and polyarticular type. The adverse reactions of short term (within 6 months) are rare, the long-term security and stability of joint recovery are subject to a large sample, multi-center long-term follow-up observational study. Etanercept can make So-JIA patient’s clinical remission, but infection and other adverse events should be strictly guarded against. We can consider Etanercept for the SO-JIA patients that the conventional treatment is of no effect or SO-JIA patients merge with MAS. But some of patients applied with Etanercept may get worse, there are no reliable predictor for this by now. The Long-term efficacy and adverse reaction require further observation. Th17-polarising conditions, indicated by significantly increased number of Th17 cells ,elevation of IL-17A production ,and upregulation of the STAT3 and RORγt. Mechanistic studies show that IL-1β represents a major mediator of MDSCs-facilitated Th17 differentiation . Conclusion: Our studies show that MDSCs have the capacity to pro inflammatory in autoimmune arthritis and can drive Th17 cell differentiation depend on IL-1β, may be a critical pathogenic factor in autoimmune arthritis. in mice (P<0.01). In addition, CAP could inhibit cell viability and promote cell apoptosis in a dose-dependent manner. Gene-chip analysis indicated that 84 genes were significantly up-regulated, whereas 24 genes were significantly down-regulated. The expressions of miR-29b and miR-15a increased over 1.5-fold, whereas the expression of miR-21 was down-expressed over 60% as determined by RQ-PCR analysis. Conclusions: CAP has a significant anti-myeloma effects, and its underlying mechanism might be inhibiting cell viability, promoting cell apoptosis and regulating related miRNAs genes expression. effectively improved the killing efficiency of T cells against KIF20A positive pancreatic adenocarcinoma cells. Results: Microscopic observations showed that DC-T cells loaded with Bi20A bispecific antibodies could spontaneously search for tumor cells and actively accumulate to KIF20A positive pancreatic cancer cells under the ADCC effect. At the same time, they showed good tumor killing activity. The 12-hour tumor cell killing activity is nearly 100 % (target ratio 30:1). Conclusion: The T cell effect mediated by bispecific antibody can effectively kill tumor cells and has good spontaneous targeting ability. Good clinical application prospect. Objective: To evaluate the safety of DCVAC/LuCa combined with pemetrexed/carboplatin in patients with stage Ⅳ non-small cell lung cancer (NSCLC). Methods: A total of 20 newly diagnosed stage Ⅳ , non-squamous, wild-type epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) negative or unknown NSCLC patients were randomized into test group (n=10) and control group (n=10). Test group received pemetrexed/ carboplatin chemotherapy (4-6 cycles), combined with DCVAC/LuCa treatment in the third cycle, followed pemetrexed monotherapy in combination with DCVAC/LuCa; control group received pemetrexed/carboplatin chemotherapy (4-6 cycles), followed pemetrexed alone. Results: The efficiency of the patients in two groups were evaluated and adverse effects (AEs) were collected and analysed. There was a significant positive correlation between DCVAC/LuCa transfusion dose and progression-free survival (PFS) (r0.773, P0.009). The common AEs in both groups were chemotherapy related leukopenia, hemoglobin decrease etc. All AEs were grade 1 or 2 according to common terminology criteria for adverse events (CTCAE) V4.03, and there were no grade 4 toxicities or treatment-related deaths. One patient in test group got non-infectious fever and body ache and returned to normal without treatment. Conclusion: In patients with stage Ⅳ NSCLC, DCVAC/LuCa therapy is well tolerated with the favourable safety. Objective: The study was conducted to observe the serum and urine levels of Lipoxin A4 (LXA4) and Nuclear Factor-kappa B(NF-κB) in pediatric Henoch-Sch ӧ nlein purpura (HSP), and their association with HSP. Methods: 99 HSP cases and 27 healthy controls (Controls) were recruited in this study. The cases were further divided into 3 groups based on the clinical features: Group 1 (37 HSP without gastrointestinal (GI) involvement and nephritis), Group 2 (30 HSP with GI involvement but without nephritis) and Group 3 (32 HSP with nephritis (HSPN)). LXA4 and NF-κB levels in each individual’s serum and urine specimens were estimated by enzyme-linked immunosorbent assay (ELISA). Results: Serum and urine LXA4 levels in Group1 and Group2 were significantly higher than Controls (P all<0.05). And LXA4 levels in Group3 were significantly lower compared with Group1 and Group2 (P all<0.05). Differently, NF-κB levels in serum and urine in Group1, Group2 and Group3 were all markedly higher compared with Controls (P all<0.05), NF-κB levels in Group3 were significantly higher than Group1 and Group2 (P all<0.05). Serum levels of LXA4 and NF-κB in HSP were significantly higher compared with urine (P both<0.01). Additionally, serum and urine LXA4 levels in HSP were negatively associated with 24-hour proteinuria and urinary mAlb (P all<0.01), NF-κB levels were positively associated with 24-hour proteinuria, urinary mAlb and D-dimer (P all<0.05). Above all, there was a negative correlation between LXA4 and NF-κB in HSP (P <0.05). Conclusions: This study supports that low LXA4 and high NF-κB levels could be potential risk markers for HSPN. And urine examination could be used in clinical practice extensively. Purposes: To investigate the serum levels and clinical significance of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in children with hyperuricemia (HUA). Methods: We included 71 children with HUA and 71 healthy children as controls. Children with HUA were divided into Group I and Group II according to whether they had a history of acute gout-like attacks (including sudden mono arthritis of rapid onset with intense pain and swelling) or not. Group I was examined twice (A, in the acute phase; B, in the remission phase). Serum IL-1β and IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Serum IL-1β and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P<0.05, respectively). Serum IL-1β and IL-6 were significantly higher in Group IA in comparison with Group IB, Group II and controls (p<0.05, respectively) as well as in Group IB and Group II compared to controls (p<0.05, respectively). In Group IB, the serum IL-1β and IL-6 concentration were higher than Group II, but there were no statistical differences (p>0.05). In addition, in children with HUA, serum IL-1β and IL-6 levels were positively associated with white blood cell count (WBC), neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate (ESR), C Reactive Protein, Blood Urea Nitrogen and serum creatinine levels (all p<0.05), but were not associated with triglycerides, total cholesterol, LDL-C or HDL-C levels (all p>0.05). Conclusion: Elevated levels of serum IL-1β and IL-6 were found in children with HUA and correlated with disease activity. Purpose: To investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria. Methods: A total of 261 HSP children-with or without nephritis-and 84 healthy control children were enrolled in this study. Of these, 126 HSP nephritis (HSPN) children were subdivided into three groups according to total urine protein in 24 hours (TUP): Group A, mild proteinuria group with TUP <25 mg/kg; Group B, moderate proteinuria group with TUP ≥25 mg/kg and <50mg/kg; Group C, severe proteinuria group with TUP≥50mg/kg. Urinary MCP-1 levels were determined by ELISA. Levels of serum creatinine (Cr), blood urea nitrogen (BUN), urinary α1-micro globulin (α1-MG), micro-albumin (mAlb), immunoglobulin G (IgG), transferrin (TRF) and TUP were performed to determine their associations with MCP-1. Results: Urinary MCP-1 was significantly higher in HSPN group in comparison with HSP group and controls (P<0.05), but no significant difference was found between the HSP group and the healthy group (P>0.05). The levels of urinary MCP-1 increased in parallel to the enhancement of total urine protein in 24 hours in HSPN patients. There were statistically significant differences among these three groups of HSPN children (p<0.05). Urinary MCP-1 correlated positively with urinary α1-MG, mAlb, IgG, TRF and TUP in HSPN, whereas no correlation was observed with serum Cr and BUN. Conclusions: MCP-1 was elevated in children with HSPN and correlated with proteinuria. Urinary MCP-1 could be used as a suitable, non-invasive biomarker to provide valuable information not only for the diagnosis of HSPN, but also for evaluation of severity of renal damage. Objective: This study aimed to compare the frequency of dual energy CT(DECT) urate crystal deposition in children with hyperuricemia (HUA). Results: deposits children with asymptomatic HUA(P<0.05). We found 54 areas of urate deposition in Joint Group, DECT urate crystal deposition was more frequently observed in the first metatarsophalangeal (MTP) joint (25.9%), ankle joint (14.8%), and calcaneus (13.0%). 24 urate deposits were found in Asymptomatic Group, DECT urate crystal deposition was more frequently observed in calcaneus (28.0%), the first MTP joint (16.0%), and the first metatarsal (16.0%). Conclusions: Urate deposition can occur in children with HUA, and these deposits occur more frequently in Joint Group. Ophthalmology. After diagnosis, 7 cases (26.9%) were performed with local therapy, 13 cases (50%) were applied with single hormone therapy, 6 cases (23.1%) were performed with hormone-immunosuppressive therapy, 9 cases (9/19, 47.4%) were recurrent in case of hormone reduction or withdrawal. Conclusion: RAU is the most common first symptom of Behcet’s disease, which gradually involves multiple organ damage. The first visit of these pediatric patients is often performed at other departments, and all doctors should pay attention to the disease. and IL-6 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results: Serum IL-1β and IL-6 levels were increased in children with HUA and were overall statistically different from the control group (P<0.05, respectively). Serum IL-1β and IL-6 were significantly higher in Group IA in comparison with Group IB, Group II and controls (p<0.05, respectively) as well as in Group IB and Group II compared to controls (p<0.05, respectively). In Group IB, the serum IL-1β and IL-6 concentration were higher than Group II, but there were no statistical differences (p>0.05). In addition, in children with HUA, serum IL-1β and IL-6 levels were positively associated with white blood cell count (WBC), neutrophil count, monocyte count, uric acid levels, erythrocyte sedimentation rate (ESR), C Reactive Protein, Blood Urea Nitrogen and serum creatinine levels (all p<0.05), but were not associated with triglycerides, total cholesterol, LDL-C or HDL-C levels (all p>0.05). Conclusion: Elevated levels of serum IL-1β and IL-6 were found in children with HUA and correlated with disease activity. Objective: To examine epidemiological, clinical, and renal involvement in Chinese children with Henoch Schonlein purpura (HSP). Methods: Retrospective study of children discharged with a diagnosis of HSP from the Ningbo Women and Children’s Hospital, between January 2013 and December 2015. Epidemiological, clinical, treatment, and outcome were collected by reviewing medical charts. Results: 936 children entered the study, M: F = 1.2:1; mean age 6.90±2.63 years. A majority of the cases were from rural areas in 81.9%. At onset, purpura was present in all cases, gastrointestinal involvement in 37%, arthritis/arthralgias in 31%, renal involvement in 40.4%, scrotal edema in 0.4%. Their mean age at presentation of HSPN was 7.13±2.78 years, which was significantly higher than the age of those without nephritis (P=0.031). Age at presentation, gastrointestinal involvement and joint involvement were the risk factors of renal involvement. Conclusion: This study suggests that in children with HSP, patients with older than 10 years, clinically gastrointestinal, and joint involvement, may be predictive of renal involvement. Background: To evaluate the serum and synovial fluid expression of osteopontin (OPN) and its possible role in the pathogenesis of Juvenile idiopathic arthritis (JIA). Methods: Fifty patients with juvenile idiopathic arthritis (JIA) were studied. Among them, 10 patients underwent synovial fluid (SF) aspiration before steroid injections. Serum samples monitored by all enrolled patients including 50 age-matched children with inguinal hernia surgery (control group). Serum and SF were measured by enzyme-linked immunosorbent assay (ELISA) for OPN. Results: Serum OPN expression was increased in active JIA compared to inactive JIA and control group, with no significant differences among the different JIA subtypes. Levels of serum in OPN were significantly correlated with hemoglobin and platelet. Conclusion: The level of OPN rises sharply in JIA active stage and JIA with joint damage. OPN may play an important role in JIA pathogenesis and the process of JIA with joint damage. Objective: To observe the related factors of juvenile idiopathic arthritis (JIA) complicated with hyperuricemia. Method: A retrospective study of the 60 JIA patients enrolled with follow-up visit for more than 1 year and performed a single factor analysis of the clinical data, lab data and special drug use of JIA with hyperuricemia (Group A), and without hyperuricemia (Group B). Results: Comparison between the two groups: the differences in age, active sacroiliitis, BMI, systolic pressure, serum creatinine, salicylazosulfapyridine application showed a statistical significance (P<0.05); the opposite results in sex, disease course, high disease activity, diastolic pressure, serum albumin, alanine aminotransferase, aspartate transaminase, triglyceride, total cholesterol, low-density application (P>0.05). Conclusion: JIA patients were obese, high systolic pressure and after salicylazosulfapyridine treatment will be more likely to accompany with hyperuricemia. Objective: This study aimed to describe HLA matched donor) without pre-treatment conditioning. The percentage of donor chimerism was 7.5% on day +14, and the patient died of respiratory failure caused by the pulmonary and intracranial infections on day +26. In this cohort, 51 patients (40.4%) were alive and 55 patients (43.75%) died from severe infections. Conclusion: We hope our study can reinforce awareness and education of medical stuff about PIDs, improve the diagnostic and therapeutic techniques, and which could improve the quality of life among patients with PIDs in the near future. Clinical manifestation : A two-month-old female presented with a chief complaint of diarrhoea and fever. The infant had enlarged alar lymph nodes in inoculate side after inoculation with BCG vaccine. She had 1-month history of recurrent fever, chronic diarrhoea, pneumonia, urinary tract infection, decreased appetite and weight loss. There was no family history of immunodeficiency or death in early infancy. Physical examination : On physical exam the patient was failure to thrive, associated with oral candidiasis, lymphadenopathy, moist rales of lung, perianal dermatitis and umbilical hernia Laboratory examination: A complete blood count revealed a haemoglobin level of 92g/L,a total white blood cell counts of 11×10 9 /L,a differential white blood cell counts of 70% neutrophils, 17% lymphocytes, and a platelet count of 317×10 9 /L.C-reactive protein was 123mg/L. The serum immunoglobulin test results showed in Table 1. The absolute lymphocyte count showed in Table 2. The lymphocyte analysis showed T - B - NK + phenotype. The sputum culture was positive for Stenotrophomonas maltophilia. The chest CT revealed interstitial pneumonia. : delins X) and the mother was carrier (Figure 2). Treatment and outcome: ADA-SCID was diagnosed when the patient was 3 months of age. She was treated with multiple antibiotics, tuberculostearic drug, anti-fungal prophylaxis and immunoglobulin replacement therapy. Then she developed purulent meningitis. After changing anti-infective treatment, she received an unrelated cord blood transplant (6/10 HLA matched donor). The prevention of GVHD included CsA, MMF and tacrolimus. The percentage of donor chimerism was 7.5% on day +14, and the patient died of respiratory failure caused by the pulmonary and intracranial infections on day +26. Objective: To study the clinical effects of Bushen Formula on chronic hepatitis B patients (CHB) treated by entecavir and the immunoregulatory mechanism of Bushen Formula. Methods: Cohort study of efficacy of Bushen Formula proceeded. 100 6 months and group was lower than that in control group(P<0.05); the change of HBsAg level in the treatment group was significantly more than that in the control group(P<0.05); the expression levels of HBV DNA and HBeAg in both groups were found statistically insignificant(P>0.05). The frequencies of Th1 and DC cells in CHB patients were significantly lower than those in healthy controls(P<0.05); the frequencies of Treg and PD-L1 + Treg cells in CHB patients were higher than those in the healthy controls(P<0.05). The frequency of Th1 cell in the treatment group was significantly increased after treatment(P<0.05), while there was no significant change in the control group(P<0.05). Conclusion: The clinical curative effects of Bushen formula combined with entecavir in CHB patients treated by entecavir were better than entecavir alone including the decrease of Chinese medicine symptom complex score and serum HBsAg. The immunoregulatory mechanism of Bushen Formula was related to the upregulation of the peripheral frequencies of Th1 and DC in CHB patients. Background: The ex vivo activation and expansion of antigen specific cytotoxic T lymphocytes (CTLs) has important meaning for antigen-recognition, antigen-epitope discovery and cytotoxicity research. Moreover, adoptive transfer of the expanded antigen specific CTLs holds promises to cure the cancer. However, all these advantages are hindered by lacking a robust way to specifically expand out CTLs. Methods: We used a hybrid of B lymphoblastic cell line and T lymphoblastic cell line (T2 cells) as a substitute of dendritic cells (DCs), together with irradiated autologous PBMC as feeder cells and rhIL-2, to activate and expand Her-2/neu specific CD8 + T cells from Her-2/ neu and HLA-A2 double positive advanced breast cancer patients in vitro. The expansion index was counted by [ 3 H]thymidine uptake, the specificity of the expanded Her-2/neu specific CD8 + T cells was verified by Her-2/neu conjugated HLA-A*0201 Dextramer, and the cytotoxicity of expanded CTLs to breast cancer cell lines was analysed by 51 Cr-release assay. Results: These Her-2/neu loaded T2 cells could stimulate CD8 + T cells to secret IFN-γ equally as DCs. With the addition of irradiated autologous PBMC as feeder cells and rhIL-2, they further expanded out Her-2/neu specific CD8 + T cells to 10 7 in 8 weeks, nearly as a clinically used amount. Furthermore, these Her-2/neu specific CD8 + T cells had good sensitivity of recognition and killing Her-2/neu expressed breast cancer cell line SK.BR.3, but not the controls. Conclusions: Her-2/neu loaded T2 cells could activate and expand out Her-2/neu specific CTLs equally as DCs. T2 cells might potentially substitute DCs to expand specific CTLs in vitro. This has important meaning in T cell immune function research, and also gives us another insight on how to rapidly obtain sufficient CTLs for adoptive cancer immunotherapy. Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral infectious disease with a high case-fatality rate. We have preliminary findings on the existence of abnormal percentage of low-density neutrophils (LDNs) and normal density neutrophils (NDNs) in the circulating blood of SFTS patients. we further explored the percentage, origins and functional roles of LDNs in SFTS. Methods: The LDNs and NDNs from circulating of SFTS or normal volunteers were purified separately. The percentage, origins and the phagocytic capability of SFTS viral (SFTSV) of LDNs were investigated by flow cytometry and real time PCR. The capacity of LDNs to secret of proinflammatory cytokines, anti-inflammatory cytokines and to damage endothelial cells were assessed by ELISA and flow cytometry. Results: We observed that the proportion of LDNs increased dramatically compared with the healthy donors and became the dominant circulating neutrophil population in SFTS patients. Interestingly, the NDNs from the normal donors could switch to active LDNs under the SFTS environment. Moreover, SFTSV load in LDNs from the severe SFTS patients was significantly higher than that from the moderated SFTS patients. In addition, the LDNs secreted much higher levels of pro-inflamtory cytokines than NDNs in SFTS and induced endothelial cell injury. Conclusion: The NDNs retained the developmental plasticity and could convert to LDNs, which contributed to the main sources of increased percentage of LDNs in SFTS. The LDNs exhibit pro-inflammation functions in SFTSV infection and may play pivotal roles in SFTS progress. Objective: Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the imbalance mechanisms are still not well determined. Notch signalling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Methods: We used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR and Immunoblotting. Results: Our results showed that DAPT effectively inhibited the mRNA and protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, after blocking the Notch signalling pathway by DAPT, we found that the proportion of Th2 cells decreased, and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. Conclusions: Our results suggest that blocking Notch signalling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients. SNP rs1799964 (OR=4.037, 95% CI 2.403-6.784) was associated with drug-resistance of TB. However, the polymorphisms of TNF-α were not related to conversion of sputum culture. Conclusion: SNPs in TNF-α promoter are associated with susceptibility and drug-resistance of pulmonary TB in Chinese Uygurs. These TNF-α polymorphisms may be considered as risk factors for active pulmonary TB. tumor-draining lymph nodes and the effective CD4 + T and CD8 + T cells in the tumor microenvironment. In addition, oHSV2 could significantly prolong the survival of tumor-bearing mice. Therefore, we concluded that oHSV2 is an effective therapeutic cancer candidate that induces an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, may be a safe and effective therapeutic agent for cancer treatment. Aim: This study aimed at identifying the in vivo and vitro effects of microRNA-29b-3p (miR-29b-3p) in Schistosoma japonicum (S. japonicum) -induced hepatic fibrosis by targeting COL1A1 and COL3A1. Methods: Thirty male Balb/c mice were divided on random into the blank group and the model group. The mice in the model group were percutaneously infected with cercariae of S. japonicum. NIH-3T3 mouse embryonic fibroblasts were obtained and designated into 6 groups: the blank, negative control (NC), miR-29b-3p mimic, TGF-β1 (10 ng/ml), TGF-β1 + NC, and TGF-β1 + miR-29b-3p mimic groups. To identify the relationships of mir-29b-3p with COL1A1 and COL3A1 dual luciferase reporter gene was conducted. The qRT-PCR was conducted to determine the expression of miR-29b-3p, COL1A1 mRNA and COL3A1 mRNA in hepatic tissues and NIH-3T3 fibroblasts. Western blotting and immunofluorescence staining were performed for observation of protein expressions of TIMP-1, HSP47, α-SMA, MMP-9, COL1A1 and COL3A1. For observing the viability and apoptosis of NIH-3T3 fibroblasts were CCK-8 assay and flow cytometry were conducted. Results: The relative expression of miR-29b-3p was significantly down-regulated in hepatic tissues of mice of the model group. MiR-29b-3p could directly target COL1A1 and COL3A1 genes. In comparison to the blank, NC, TGF-β1 and TGF-β1 + NC groups, NIH-3T3 fibroblasts exhibited miR-29b-3p and MMP-9 up-regulation in the miR-29b-3p mimic group, while the expressions of TIMP-1, HSP47, α-SMA, COL1A1 and COL3A1 were obviously down-regulated. Furthermore, in comparison to the blank, NC, TGF-β1 and TGF-β1 + NC groups, NIH-3T3 fibroblasts in miR-29b-3p mimic group depictedlower cell viability and a higher apoptosis rate. Conclusion: Together these data provide a strong evidence that miR-29b-3p could relieve S. japonicum -induced hepatic fibrosis by down-regulation of COL1A1 and COL3A1. Objective: Identifying the effect of on the expression of PD-L1 of NSCLC by transfection and siRNA methods and exploring the associated mechanisms. Methods: qRT-PCR and Western blot evaluate Con group ( P <0.05). iRNA knockdown of c-MYC caused a reduction in the level of PD-L1 mRNA and protein compared to the Con group ( P <0.05). Conclusion: BIN1 could reverse the PD-L1-mediated immune escape via inhibiting c-MYC pathway in NSCLC. results between the groups with respect to rs1518110, rs1518111, rs1554286, rs1800890 and rs6667202 (all P>0.05). Conclusion: In summary, IL-10 rs3024498 polymorphism might contribute to SLE susceptibility and several clinical phenotypes. cancer tissues. Moreover, ETAR expression was found in both HSCs and HSECs. Finally, the statistical analysis revealed that the number of positive ETAR cells was correlated with the clinical index platelets (PLT), alanine transaminase (ALT) and diameter of portal vein. Conclusion: Endothelin receptors express differently in liver cirrhosis and liver cancer tissues and play a role in hepatic diseases by affecting HSCs and HSECs. to enhance the activity of cytokine-induced killer (CIK) cells for immunotherapy. vs 27.31%±2.69%, 8.74%±2.41%, 38.65%±21.30%, all p<0.05; 20:1: 91.97%±4.21% vs 34.27%±0.85%, 11.54%±2.78%, 48.32%±11.72%, all p<0.05; 40:1: 91.84%±9.28% vs 50.67%±1.30%, 23.73%±11.07%, 52.89%±12.26%, all p<0.05). Cell phenotypes were not significantly different between the CIK cells with and without IL-24 treatment (p>0.05). Apoptotic and necrotic cells were obviously increased in after IL-24 treatment under transmission electron microscope. Conclusion: IL-24 can obviously enhance the cytotoxic activity of CIK cell. and Will also be NK cells and immune response, the relationship of NK cells is discussed and anti-aging, autism, epilepsy, aplastic anaemia, diabetes, lupus erythematosus (sle), and the NK cell immunotherapy was prospects forecasted too in this paper. We to and on were in from different and cytometry were to allogeneic T In the same strain, BMDCs of neonates were significantly less matured than BMDCs from 3w or 8w (p<0.01). At baseline, BMDCs secreted no IL-6, IL-12 and TNF-α. LPS stimulation resulted in increased production of TNF-α in both C57BL/6 and BALB/c mice (p<0.01) of each age group. However, TNF-α secreted by C57BL/6 was much higher than BALB/c of same age (p<0.01). In the same strain, the level of TNF-α in neonates was significantly lower than other age groups (p<0.01). The secretion of IL-6 and IL-12 was similar to TNF-α. However, BMDCs from BALB/c neonatal mice produced lower level of IL-12 before and after LPS stimulation. allogeneic apoptosis p<0.01). Conclusions: We found that the function of BMDCs from different strains and ages of mice is different. BMDCs from neonates were less mature and less sensitive to LPS stimulation. These results suggested that strain and age of mice could shape the immune responses via their effects on DCs. The intestinal microbiota plays a central role in certain physiological functions that contribute to the maintenance of symbiotic relationship with human hosts, such as metabolism, nutrition, entero protection and immunoregulation function, etc. Nevertheless, recent studies have revealed that the alerted gut microbiome in patients with chronic kidney disease (CKD) results in exacerbating the progression of CKD and CKD-related complications, which is distinct from the role of symbiotic microbiota. This paper is intended to provide an overview of the connections between intestinal flora and CKD. In addition, the main mechanisms and the potential intervention strategy are also carried on the review and discussed. we also analysed the evolutionary branch and intercommunication in CI and CHD group. Conclusion: There was a confusion and low similarity in intestinal guts of CI and CHD, and intestinal guts may be a potential marker of above disease. Objective: To understand the detection rate and gene phenotypic characteristics of high-risk children in Guangzhou. Methods: 2ml (EDTA anticoagulant) of blood were collected from 6171 cases with high-risk thalassemia children. The gene mutation type of children was determined by PCR and reverse point hybridization. Results: 1303β-thalassemia cases were detected in 6171 cases (1303/6171,21.11%). 17 kinds of gene mutation detection and 35 genotypes were detected. The most common 7 kinds of β-thalassemia gene mutations were CD41-42, IVS-2-654, -28, CD17, CD71-72, beta E, and CD43,which accounting for 38.83%, 27.24%, 9.82%, 9.06%, 2.23%, 2.15%, 1.15%,respectively.These 7 kinds of gene mutations contributed to 90.48% of all mutated genes. 1218 cases of heterozygote accounting for 93.48%, 32 cases of homozygous (2.46%) and 53 cases (4.06%) double heterozygote were detected. Conclusion: The type of beta thalassemia gene mutations in children was diversity in Guangzhou region. The main type of β-thalassemia is heterozygous. It is a great significance to reduce the birth of serious thalassemia children through strengthen the premarital and pregnancy thalassaemia screening and prenatal diagnosis. Compared with the SLE group, the increase of WBC had statistical significance (P < 0.05) in SLE with varicella while the levels of IgG, IgA, C3 and C4 in serum decreased with statistical significance (P < 0.05). Conclusion: Varicella-zoster virus can induce the changes of immune system-related indexes in systemic lupus erythematosus patients. Objectives: Macrophage activation syndrome (MAS) is a severe, potentially fatal complication of rheumatoid disease, especially in the systemic onset juvenile idiopathic arthritis (SoJIA). We investigated the clinical characteristics of 31 Chinese MAS cases with SoJIA and detected the perforin A91V gene in part cases. Methods: Clinical characteristics of 31 SoJIA with MAS cases in the last nine years in our institute were retrospectively analysed. Gene-specific polymerase chain reaction (PCR) primers were used to analyse the perforin A91Vgene polymorphism. Results: 31 SoJIA cases were associated with MAS. No specific medication was identified as trigger. 83% cases had infections prior to MAS. Clinical manifestations of MAS included persistent fever (100 %), hepatosplenomegaly (93.55%), lymphadenopathy (64.52%), and liver dysfunction (83.87%). Laboratory features included pancytopenia (41.9%), increased serum ferritin (87.10%), triglycerides (74.19%) and lactic dehydrogenase (87.10%). Hemophagocytosis were found in 27 cases (87.10%). The levels of NKcell in MAS patients was statistically below than the SoJIA and control group. The perforin A91V variant gene was detected in twenty cases, but no mutation was found. Glucocorticoid, intravenous immunoglobulin, immunoimpressive therapy were effective. After treatment, 28cases (90.32%) were in remission, while 3 out of 31 cases died with a mortality of 9.68%. Conclusions: MAS is a life-threatening complication of SoJIA. Most cases were preceded by infection. Unremitted fever, progressive hepatosplenomegaly, lymphadenopathy, cytopenias, elevated serum liver enzymes, significantly increased serum ferritin are the main feature. Prompt recognition and treatment is the key to improve prognosis. The perforin gene mutations in our patients need more research. The numbers of the cases need expend.

. The time gradient results show that the T cells loaded with Bi20A bispecific antibodies have a significantly higher ability to kill tumor cells than unloaded T cells. At the same time, the results also showed that the cells cultured by DC-T mixed culture showed a significant CTL effect after the Bi20A bispecific antibody was loaded, and the targeting effect was stronger.  Rheumatology and Immunology, Ningbo Women and Children's Hospital, 339 Liuting Street, Ningbo, Zhejiang 315000, China 2 Medicine School, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang 315000, China Purpose: To investigate the urinary monocyte chemoattractant protein-1 (MCP-1) levels and clinical significance in Henoch-Schonlein purpura (HSP) children with and without nephritis and determine the association of MCP-1 with proteinuria.

Methods:
A total of 261 HSP children-with or without nephritisand 84 healthy control children were enrolled in this study. Of these, 126 HSP nephritis (HSPN) children were subdivided into three groups according to total urine protein in 24 hours (TUP): Group A, mild proteinuria group with TUP <25 mg/kg; Group B, moderate proteinuria group with TUP ≥25 mg/kg and <50mg/kg; Group C, severe proteinuria group with TUP≥50mg/kg. Urinary MCP-1 levels were determined by ELISA. Levels of serum creatinine (Cr), blood urea nitrogen (BUN), urinary α1-micro globulin (α1-MG), micro-albumin (mAlb), immunoglobulin G (IgG), transferrin (TRF) and TUP were performed to determine their associations with MCP-1.
Results: Urinary MCP-1 was significantly higher in HSPN group in comparison with HSP group and controls (P<0.05), but no significant difference was found between the HSP group and the healthy group (P>0.05). The levels of urinary MCP-1 increased in parallel to the enhancement of total urine protein in 24 hours in HSPN patients. There were statistically significant differences among these three groups of HSPN children (p<0.05). Urinary MCP-1 correlated positively with urinary α1-MG, mAlb, IgG, TRF and TUP in HSPN, whereas no correlation was observed with serum Cr and BUN.
Conclusions: MCP-1 was elevated in children with HSPN and correlated with proteinuria. Urinary MCP-1 could be used as a suitable, non-invasive biomarker to provide valuable information not only for the diagnosis of HSPN, but also for evaluation of severity of renal damage.

Women and Children's Medical Center, Guangzhou Medical University, China
Objective: This study aimed to describe the frequency and clinical spectrum of 126 patients with primary immunodeficiency diseases (PIDs) in Guangzhou Women and Children's Medical Center from China over the last 10 years.

Method:
We retrospectively analysed the records of all the patients identified to have specific PID from January 2006 to December 2015. The diagnosed patients were classified according to guidelines of International Union of Immunological Society (IUIS) into nine different subgroups.

Results:
In total, 126 children (88.9% males) from 125 unrelated families met the criteria and were included. PIDs spectra were as follows:51 patients were diagnosed as "Predominant antibody deficiencies(40.5%), "43(34.1%) with "Combined immunodeficiencies," 15 (11.9%) with "Congenital defects of phagocyte number, function, or both,"13(10.3%) with "Combined immunodeficiencies with associated or syndromic features", 2(1.6%) with "diseases of immune dysregulation" and 2(1.6%) with "Autoinflammatory disorders". Patients from Guangdong and Guangxi provinces accounted for 49.2% (n = 62). The patients aged from first day of life to 14 years old. The median age of onset at presentation was 2.5months (range 1 day -96 months) and the median time to the diagnosis was 12 months (range 2 -168 months). Genetic analysis was performed in 97 patients (77%). 57 different mutations were identified from 9 pathogenic genes in 64 unrelated patients. 4 novel mutations were detected. 26 carriers were identified from 21 families. Pneumonia was the most common infections (n=90,71.4%). 61 patients had infections in two to four organs (48.4%). Autoimmune haemolytic anaemia was the most common manifestation of autoimmunity. None of the patients in this study developed malignancy. 56 patients (44.4%) received intravenous broad-spectrum antibiotics and 72 patients (57.1%) received intravenous immunoglobulin (IVIG). Only one patient with ADA-SCID received an unrelated cord blood transplant (6/10 HLA matched donor) without pre-treatment conditioning. The percentage of donor chimerism was 7.5% on day +14, and the patient died of respiratory failure caused by the pulmonary and intracranial infections on day +26. In this cohort, 51 patients (40.4%) were alive and 55 patients (43.75%) died from severe infections.

Women and Children's Medical Center, Guangzhou Medical University, China
Clinical manifestation: A two-month-old female presented with a chief complaint of diarrhoea and fever. The infant had enlarged alar lymph nodes in inoculate side after inoculation with BCG vaccine. She had 1-month history of recurrent fever, chronic diarrhoea, pneumonia, urinary tract infection, decreased appetite and weight loss. There was no family history of immunodeficiency or death in early infancy.
Physical examination: On physical exam the patient was failure to thrive, associated with oral candidiasis, lymphadenopathy, moist rales of lung, perianal dermatitis and umbilical hernia Laboratory examination: A complete blood count revealed a haemoglobin level of 92g/L,a total white blood cell counts of 11×10 9 /L,a differential white blood cell counts of 70% neutrophils, 17% lymphocytes, and a platelet count of 317×10 9 /L.C-reactive protein was 123mg/L. The serum immunoglobulin test results showed in Table 1. The absolute lymphocyte count showed in Table 2. The lymphocyte analysis showed T -B -NK + phenotype. The sputum culture was positive for Stenotrophomonas maltophilia. The chest CT revealed interstitial pneumonia.
Genetic test: Molecular studies on her blood DNA revealed the patient to be a compound heterozygote for 2 different mutations in ADA gene. One of which was a singlenucleotide substitution (905C→T) predicted to lead to a single amino acid substitution (S302F), the father was carrier (Figure 1). The second of which was a singlenucleotide duplication (747 dup T) predicted to lead to a nonsense mutation (N250_R251 delins X) and the mother was carrier (Figure 2). Treatment and outcome: ADA-SCID was diagnosed when the patient was 3 months of age. She was treated with multiple antibiotics, tuberculostearic drug, anti-fungal prophylaxis and immunoglobulin replacement therapy. Then she developed purulent meningitis. After changing anti-infective treatment, she received an unrelated cord blood transplant (6/10 HLA matched donor). The prevention of GVHD included CsA, MMF and tacrolimus. The percentage of donor chimerism was 7.5% on day +14, and the patient died of respiratory failure caused by the pulmonary and intracranial infections on day +26.

Laboratory of Cellular Immunity Shuguang Hospital Affiliated to TCM, Shanghai, China
Objective: To study the clinical effects of Bushen Formula on chronic hepatitis B patients (CHB) treated by entecavir and the immunoregulatory mechanism of Bushen Formula.

Methods:
Cohort study of clinical efficacy of Bushen Formula was proceeded. 100 CHB patients treated by entecavir for 6 months or more were collected in outpatient of department of hepatopathy in Shuguang Hospital from February 2014 to December 2016. 100 CHB patients were categorized into the treatment group (52 patients) and the control group (48 patients). The patients in the treatment group received Bushen Formula combined with entecavir, and the patients in the control group continued with entecavir alone. The observation period was 24 weeks. The serum levels of ALT, AST, HBV DNA, HBsAg, HBeAg and the Chinese medicine symptom complex score were calculated. 34 CHB patients treated by entecavir for 6 months or more were collected from April 2015 to December 2016, and they were randomly categorized into the treatment group (15 patients) and the control group (19 patients). The observation period was 24 weeks. In addition, 9 healthy controls were enrolled. Serum ALT, AST, HBV DNA, HBsAg and HBeAg levels were tested. The peripheral frequencies of Th1, Treg, DC and the expression of PD-1/PD-L1 on T cells and DC were detected by flow cytometry.

Results:
The results of cohort study of clinical efficacy of Bushen Formula after treatment showed that the Chinese medicine symptom complex score in both groups was decreased, and the score in treatment   Oncolytic viruses are promising treatments for many kinds of solid tumors. Oncolytic herpes simplex virus type 2 (oHSV2) is an oncolytic agent that encodes granulocyte-macrophage colony-stimulating factor and is genetically engineered to selectively replicate in and kill tumor cells, while sparing normal cells. In vitro, oHSV2 could infect most of the human and murine tumor cell lines and was highly oncolytic. Initial oHSV2 infection, cell necrosis, and subsequent oHSV2 propagation within the tumor cell led to a cascade of host responses, reflective of natural anti-viral immune responses. Although anti-viral immune responses limited oHSV2, induced the anti-tumor immunity. There was a study showed that oHSV2 treatment not only slowed down the growth of tumors without causing weight loss but also induced an elevation of NK cells and mild decrease of Tregs in spleen. Another study also found oHSV2 was able to reduce the ratio of spleen MDSC and Tregs in the experimental mouse, simultaneously increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4 + T and CD8 + T cells in the tumor microenvironment. In addition, oHSV2 could significantly prolong the survival of tumor-bearing mice. Therefore, we concluded that oHSV2 is an effective therapeutic cancer candidate that induces an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, may be a safe and effective therapeutic agent for cancer treatment.