Background: Psoriasis vulgaris is a chronic inflammatory skin disease which occur at any age. It can be clinically classified into two age-onset subtypes: early-onset psoriasis (EOP;＜40 years) and late-onset psoriasis (LOP; ≥40 years). More evidence showed EOP and LOP have different genetic architecture, notably the risk allele human leukocyte antigen (HLA)-C*06:02 located within the major histocompatibility complex (MHC) region, which was reported to be the outstanding variant associated with EOP. However, genetic structure of EOP and LOP have not been fully elucidated. Objective: To investigated HLA genetic heterogeneity between EOP and LOP in China. Methods: We first calculated the MHC-based heritability of EOP and LOP respectively.Then, we conducted a large-scale, stratified analysis including 7,097 EOP, 1,337 LOP patients, and 9,906 healthy controls by using MHC target sequencing data from a previousstudy. Results: We observed that HLA alleles collectively explained a larger heritability of EOP (27.4%) than LOP (11.3%).Further association analysis identified three independent loci (HLA-C*01:02, p=6.70×10−8 ; HLA-A amino acid position 9, p=3.27×10−17 ; and HLA-A amino acid position 161, p=5.75×10−10 ) that confer specific susceptibility to EOP. Our data also confirmed HLA-C*06:02 as an independent psoriasis-associated variant, contributing a higher degree of risk to EOP than LOP. Moreover, case-case analysis confirmed that HLA-C*06:02-positive psoriasis patients have earlier onset. Conclusion Our analysis indicating that different genetic background underlie the EOP and LOP. We believe these findings will serve to predict psoriasis risk in the future and facilitate clinical decision.

Objective: To investigation HER2 status in gastric adenocarcinoma of Chinese and contributing factors to the HER2 expression. Methods: HER2 status of 40 842 gastric adenocarcinomas and clinical data were retrospectively collected from 23 hospitals dated from 2013 to 2016. The association between HER2 positivity and clinicopathologic features was analyzed. Results: Of the 40 842 patients the median age was 62 years, the male female ratio was 2.6∶1.0. The rate of HER2 positivity was 8.8% (3 577/40 842). HER2 expression was related to the tissue type, tumor location, Lauren classification and tumor differentiation (P values: 0.009, 0.001, <0.01 and <0.01, respectively). Different HER2 expression status was observed between primary and recurrent tumors in 7.6% (48/635) cases. The rates of HER2 positivity ranged from 2% to 10% among different institutions. The rates of HER2 FISH amplification were dramatically different among the 23 hospitals (0-100%) with an average rate of 10% (810/8 156) in patients with HER2 IHC 2+ . Conclusions HER2 expression is associated with clinicopathologic characteristics. HER2 re-assessment of tumor tissue and use of in situ hybridization techniques increase HER2 positivity. The current retrospective study should reflect the HER2 status in gastric adenocarcinoma of Chinese patients.

OBJECTIVE: To evaluate the recovery of patients with end-stage renal disease (ESRD) receiving kidney transplant from cardiac death donors, and to assess graft survival in China from this type of donor. METHODS: A total of 48 cases of patients with ESRD have received the kidneys from cardiac death donors in our hospital between February 2010 and March 2012. We retrospectively analyzed data on the preoperative and postoperative serum creatinine concentrations, on the survival of recipients and allografts with a view to investigating prognoses after this type of kidney transplant. RESULTS: Primary non-function (PNF) did not occur in any of the 48 recipients. Delayed graft function (DGF) occurred in 18 of 48 (37.5%) of kidneys from cardiac death donors, but the occurrence of DGF did not adversely influence patient's survival (P=0.098) or graft survival (P=0.447). Seven of 48 (14.6%) recipients lost their graft. Over a median follow-up period of 8 months (range 0.5-23 months), 39 of 41(95.1%) recipients' graft function had fully recovered. The actuarial graft and patient's survival rates at 1, 3, 6 and 12 months after transplantation were 95.7%, 93.0%, 90.0%, 87.5%, and 100%, 94.9%, 90%, 87.5%, respectively. CONCLUSION As the legislation of donation after brain death (DBD) has not been ratified in China, the use of kidneys from cardiac death donors might be an effective way to increase the number of kidneys available for transplantation here. Our experience indicates good short- and mid-term outcomes with transplants from cardiac death donors.
Adult ; Brain Death ; Cadaver ; Death, Sudden, Cardiac ; Delayed Graft Function ; epidemiology ; Female ; Graft Survival ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Tissue Donors ; statistics & numerical data

The positive human leukocyte antigen (HLA) antibody present in kidney transplant recipients affects both surgery and rejection, and also affects the long-term survival of the transplanted kidney. During the third kidney transplant, bilateral axillary fossa and iliac vessel were destroyed. It was very difficult for selection or separation of surgical vessels because the adhesions and scar formation was easy to damage blood vessels and intestinal tubes. A case with strong positive HLA antibody undergoing the third kidney transplant in our hospital was successfully solved the problems, such as less transplant space and vascular scar adhesion. Rituximab, rabbit anti-human thymocyte immunoglobulin, and methylprednisolone treated-antibodies were used in the operation. The immune function test was used to develop individualized treatment after the operation. The postoperative creatinine and urine volume tended to be stable, and the 16-month follow-up renal function was good.
Antibodies ; Humans ; Kidney ; Kidney Diseases ; surgery ; Kidney Transplantation ; Nephrectomy ; Rituximab

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.