Costimulatory signals have become a hot field in immunological researches. As co-inhibitory molecules, programmed death-1 ( PD-1) and its ligands (PD-1/PD-L) have been demonstrated to play an important role in autoimmune disease, organ transplant rejection, microorganism infection, tumor immune escapes etc. . In recent years,some studies about PD-1/PD-L pathway in ophthalmology have been curried out and reported. Some changes were found in PD-1/PD-L pathway, such as ocular immunologic diseases, ocular infectious diseases, ocular tumors, immune privilege in ocular tissues and so on. Through the research on PD-1/PD-L pathway,we can further understand the pathogenesis of some ocular diseases and find new methods for their prevention and treatments. This article reviewed the recent advances in PD-1/PD-L pathway in ophthalmological physiopathology.

BACKGROUND:Core decompression may provide insufficient support for the subchondral bone in the treatment of early avascular necrosis of the femoral head and increase the risk of fracture and colapse. Quadratus femoris implantation cannot only provide good biological support, but also promote the revascularization at necrotic regions, thus repairing the necrosis of femoral head. OBJECTIVE: To compare the clinical effects of core decompression with bone paste implantation and core decompression with quadratus femoris implantation on early and middle-stage avascular necrosis of the femoral head. METHODS:Eighty-three patients with early avascular necrosis of the femoral head (92 hips) admitted at the Department of Orthopedics, the First Affiliated Hospital of Zhengzhou University, China, from January 2009 to January 2012 were enroled and divided into groups of core decompression with bone paste implantation (46 cases, 49 hips) and core decompression with quadratus femoris implantation (37 cases, 43 hips) that were respectively injected with bone meal and autogenous bone and osteoinductive materials. RESULTS AND CONCLUSION: Al involved patients were folowed up. After 1 year of treatment, Harris scores in the two groups were both increased (P < 0.05). But the Harris score of core decompression with bone paste implantation group was lower than that of core decompression with quadratus femoris implantation group (P < 0.05). After 3 years of treatment, X-ray scores in the core decompression with quadratus femoris implantation group were significantly higher than those in the core decompression with bone paste implantation group (P < 0.05). These findings indicate that compared with core decompression with bone paste implantation, core decompression with quadratus femoris implantation is better to prevent femoral head colapse, improve hip function and delay the process of osteonecrosis of the femoral head.

Background Some aboard studies showed that polyatomic pathway play an important role in the microsvasculopathy of type 2 diabetes,and sorbitol dehydrogenase (SDH) gene is involved in the pathogenesis of diabetic retinopathy(DR).There is no relevant research at home up to now.Objective This study was to investigate the correlation of sorbitol dehydrogenase (SDH) G-888C gene polymorphism with diabetic retinopathy (DR) in type 2 diabetes mellitus.Methods The SDH genotypes were determined by polymerase chain reactionreaction fragment length polymorphism (PCR-RFLP) in 187 patients with diabetes and 123 normal contrels.Patients were divided into two groups depending on the presence or absence of DR(DR:n=118;NDR:n=69).The frequencies of SDH genotype and allele were assayed and compared among these groups.This study was approved by Ethic Committee of Guangdong General Hospital.Written informed consent was obtained from each individual prior to any relevant medical procedure.Results The disease course in the DR group was significantly longer than that in NDR group(t=2.070,P=0.042),and other clinical features in both groups were non-significant (all P>0.05).The genotype frequencies in the DR group,NDR group and normal control group were 24.6%,8.7% and 8.1%,respectively,and frequencies of the G allele were 42.4%,25.4% and 29.7%,showing statistically significant differences among these three groups.The GG genotype and G allele frequencies were significantly higher in the DR group than those in the NDR group and normal control group (GG:P=0.007,P=0.001;G:P=0.001,P=0.004).There were no significant differences in the frequencies of the GG genotype and G allele between the NDB group and normal control group ( P>0. 05) as well as the proliferative DR group and non-proliferative DR group (P>0.05).Conclusion SDH G-888C gene polymorphism is associated with the development of diabetic retinopathy in southern Chinese.

Objective To investigate the impacts of pyruvate kinase M2 isoform (PKM2) silencing on the radiosensitivity of lung adenocarcinoma cell line (A549 cells) and the radiation synergy of xenografts, and to explore their mechanisms. Methods Plasmid pshRNA?PKM2 for interference with PKM2 expression was transfected into A549 cells, and empty vector?transfected cells and untransfected cells were set as con?trols. The silencing efficiency of pshRNA?PKM2 and the expression level of microtubule?associated protein 1 light chain 3(LC3) were measured by Western blot assay. The radiosensitizing effects in A549 cells and xen?ografts after PKM2 silencing were determined by colony?forming assay and xenografts growth curves. Autoph?agy formation in A549 cells and xenografts was analyzed by transmission electron microscopy, and the ex?pression level of PKM2 in xenografts was measured by immunohistochemistry. Comparison between groups was made by Student′s t?test, and the body weights of nude mice and xenograft volumes were subjected to a?nalysis of variance for continuous variables. Results Stable A549 cell lines transfected with pshRNA?PKM2 were successfully produced. Transfection with pshRNA?PKM2 significantly down?regulated PKM2 expression in A549 cells and xenografts (P= 0?? 001;P= 0?? 000). The sensitizer enhancement ratios for A549 cells and xenografts were 1?? 47 and 2?? 00, respectively. Interference with PKM2 expression enhanced radiation?in duced autophagy formation and significantly increased the ratio of LC 3 ? II / I ( P= 0.000 1 ) . Conclusions Silencing of PKM2 expression may enhance the radiosensitivity of A549 cells and xenografts by regulation of autophagy, which holds promise for becoming an effective radiosensitizing target for non?small cell lung canc?er, but still needs to be confirmed by further studies.

Objective:To investigate the effects and underlying mechanisms of XRCC3 on esophageal squamous-cell carcinoma (ESCC) radiotherapy response. Methods:Expression levels of XRCC3 were detected by reverse transcription PCR, Western blot, and immunohistochemistry. We knocked down XRCC3 with lentiviral infection in ESCC cells. Cell apoptosis was examined by flow cytom-etry. DNA damage and telomere dysfunction-induced foci were determined by immunofluorescence. Results:The expression levels of XRCC3 in ESCC cells and tissues were higher than those in normal esophageal epithelial cells and corresponding adjacent noncancer-ous esophageal tissues. Knockdown of XRCC3 in ESCC cells substantially increased the therapeutic efficacy of radiation. We demon-strated that the radiation resistance of XRCC3 was attributed to the XRCC3-maintaining telomere stability, which reduced ESCC cell death through radiation-induced apoptosis. Conclusion: Our data suggested that XRCC3 protects ESCC cells from ionizing radia-tion-induced DNA damage and death by enhancing telomere stability. Thus, XRCC3 can be used as a promising therapeutic target for ESCCs.

Objective To investigate the clinical and pathological characteristics of IgA nephropathy (IgAN) with macrohematuria (MH).Method 1512 consecutive patients with biopsyproven IgAN diagnosed from January 2006 to December 2011 were enrolled,and divided into MH group and control group respectively,according to whether there existed episodes of MH before renal biopsy.The clinical and pathological characteristics were compared between two groups.Patients in MH group were then divided into three groups according to the interval from the last episode of MH to renal biopsy to clarify the concomitant clinicopathological changes associated with occurrence of MH.Results The rate of MH in history was 22.1％.MH group patients had significantly lower serum creatinine,slighter proteinuria,lower prevalence of hypertension and heavier microhematuria than control group (all P ＜ 0.001).The prebiopsy durations were similar in two groups (P=0.627).In MH group,chronic pathological indicators,including global/segmental sclerosis,tubule atrophy/interstitial fibrosis were all slighter (all P＜ 0.001),whereas activity indicators,including necrosis lesions,crescents and mesangial proliferation were all more severe compared with control group (all P ＜ 0.05).Those who underwent renal biopsy within 30 days of the last episode of MH had more severe proteinuria and microhematuria,higher prevalence of necrosis lesions,more severe crescents formation,and endothelial proliferation (all P ＜ 0.05).Conclusions IgAN patients with MH in history have relatively milder clinical and chronic pathological manifestations,however more active pathological changes especially in those who suffer episode of MH recently.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, as it extends survival and increases quality of life in these patients. However, chronic allograft injury continues to be a major problem, and leads to eventual graft loss. Early detection of allograft injury is essential for guiding appropriate intervention to delay or prevent irreversible damage. Several advanced MRI techniques can offer some important information regarding functional changes such as perfusion, diffusion, structural complexity, as well as oxygenation and fibrosis. This review highlights the potential of multiparametric MRI for noninvasive and comprehensive assessment of renal allograft injury.
Allografts ; Diffusion ; Fibrosis ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Magnetic Resonance Imaging ; Oxygen ; Perfusion ; Quality of Life ; Transplants

This paper introduced the key points in fabricating anterior esthetic restorations with all ceramic materials, including pre-operative smile design, standard tooth preparation, provisional restoration fabrication, all ceramic materials selection, all ceramic restoration bonding, ceramic crack and fracture prevention. And then, the authors summarized and reviewed the clinical common problems in anterior esthetic restorations.
Ceramics ; Dental Porcelain ; Esthetics ; Humans

BACKGROUNDInvasive fungal infections such as candidiasis and mold infections cause significant morbidity and mortality in seriously ill patients. Micafungin is an echinocandin antifungal agent with potent activity against most species of Candida and Aspergillus. We did this meta-analysis to clarify whether micafungin offers superior efficacy and safety compared with other antifungal agent for treating infections associated with invasive candidiasis.

METHODSWe did a meta-analysis of randomized controlled trials to examine whether micafungin has superior efficacy and safety compared with other antifungal agents recommended by the treatment guidelines for fungal infection. Seven trials involving 2913 patients were included in this analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated.

RESULTSMicafungin was associated with significantly better treatment success compared with the comparator antifungal agents (modified intention to treat, 2851 patients; random-effects model, OR 1.20, 95%CI 1.00 - 1.45, P = 0.0487). In addition, micafungin was more effective than the comparators for antifungal prophylaxis of neutropenic patients undergoing hematopoietic stem cell transplantation (OR 1.47, 95%CI 1.08 - 2.00, P = 0.01). Although there was no significant difference between the compared regimens in terms of the incidence of adverse drug effects (OR 0.94, 95%CI 0.77 - 1.11), fewer patients treated with micafungin withdrew from the studies because of adverse events (OR 0.64, 95%CI 0.44 - 0.94).

CONCLUSIONSMicafungin has a good safety and tolerability profile, with an efficacy at least comparable to the other antifungal agents. Micafungin offers advantages over other agents for antifungal prophylaxis. Micafungin offers an appropriate alternative for antifungal prophylaxis rather than the treatment of invasive candida infections.

Antifungal Agents ; adverse effects ; therapeutic use ; Candidiasis, Invasive ; drug therapy ; Echinocandins ; adverse effects ; therapeutic use ; Humans ; Lipopeptides ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVETo evaluate the clinical significance of IgH and TCR gamma gene rearrangement in plasma free DNA in patients with non-Hodgkin Lymphoma (NHL).

METHODSPlasma free DNA in 74 patients with NHL were extracted and identified by Globin gene. IgH (FR3A/VLJH), TCR gamma (TVG/TJX) clonal rearrangements were amplified by PCR and compared with results of mononuclear cell DNA and pathological biopsy sample DNA.

RESULTSPlasma free DNAs were successfully obtained from 58 cases (35 B-NHL and 23 T-NHL) of newly diagnostic, refractory and relapsed NHL out of total 74 patients (78.4%), but not found in the rest 16 patients in remission. Of 35 B-NHL cases, 31 showed IgH rearrangement (88.6%), and none with TCR gamma rearrangement; of 23 T-NHL cases, 8 showed TCR gamma rearrangement (34.8%), and 2 with IgH gene rearrangement synchronously. In comparison with the results of IgH and TCR gamma gene rearrangement in biopsy samples in 30 B-NHL cases, 26 cases in plasma free DNA (86.7%) and 24 in biopsy samples (80%) were positive (P > 0.05). In 20 T-NHL patients, 7 cases in plasma cell-free DNA (35%) and 6 cases in biopsy samples (30%) were positive (P >0.05).

CONCLUSIONSTumor-derived DNA could be detected in plasma from underlying cancer patients. For NHL patients, detecting IgH and TCR gamma gene rearrangement in plasma free DNA has the same clinical significance as in biopsy samples.

Adolescent ; Adult ; Aged ; Child ; DNA ; blood ; Female ; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Lymphoma, Non-Hodgkin ; blood ; genetics ; Male ; Middle Aged ; Young Adult