IntroductionAmong various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China.MethodsClinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed.ResultsIn the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P = 0.007).ConclusionsThere were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.

ZC3H13 is a canonical CCCH zinc finger protein, which harbors a somatic frame‐shift mutation in colorectal cancer (CRC). However, its expression and biological function were still uncertain. In the current study, we found that ZC3H13 was served as a tumor suppressor in CRC cells, which decreased the expression of Snail, Cyclin D1, and Cyclin E1, and increased the expression of Occludin and Zo‐1 through inactivating Ras–ERK signaling pathway. Furthermore, reduction of ZC3H13 associated with advanced TNM stage (p = 0.02), positive regional lymph node metastasis ( p = 0.01). Taken together, the current study indicated that ZC3H13 may be an upstream regulator of Ras–ERK signaling pathway and suppressed invasion and proliferation of CRC.

The fast-developing field of nanotechnology provides unprecedented opportunities for the increasing demands of biomedicine, especially for cancer diagnostics and treatment. Here, novel multifunctional zero-dimensional-two-dimensional (0D-2D) RGD-QD-MoS nanosheets (NSs) with excellent fluorescence, photothermal conversion, and cancer-targeting properties were successfully prepared by functionalizing single-layer MoS NSs with fluorescent quantum dots (QDs) and arginine-glycine-aspartic (RGD) containing peptides. By using RGD-QD-MoS NSs as a multifunctional theranostic agent, targeted fluorescent imaging and photothermal therapy (PTT) of human cervical carcinoma (HeLa) cells were achieved. Moreover, HeLa tumors in mouse models can be fluorescently imaged and completely eradicated by photothermal irradiation using a low power NIR laser, due to the effective accumulation of RGD-QD-MoS NSs at the tumor sites through the RGD-integrin targeting and the enhanced penetration and retention (EPR) effect. Without exhibiting any appreciable toxicity to treated cells or animals, RGD-QD-MoS NSs have been demonstrated as promising multifunctional theranostic agents for cancer imaging and therapy.

BackgroundSelf-locking stand-alone cages (MC+) and cage-with-pate fixation system are 2 different surgical methods used in anterior cervical discectomy and fusion (ACDF), but few systematic comparative studies comparing the 2 methods in treating multilevel cervical spondylotic myelopathy (MCSM) have been published.Material/MethodsSixty-two patients with MCSM who underwent multilevel ACDF were enrolled and completed at least a 3-year postoperative follow-up. The operative time, intra-operative blood loss, and clinical and radiological results were compared between the MC+ self-locking cages group and the cage-with-plate fixation group. Clinical parameters, including VAS for neck pain, Japanese Orthopedic Association (JOA) score, and neck disabled index (NDI), were evaluated. Surgical results according to Odom’s criteria and postoperative dysphagia status, C5 nerve root palsy, and loosening of the instrumentation were recorded. Postoperative radiological results, including fusion rates, fusion segmental Cobb’s angle (FSC), cervical lordosis, fusion segmental height (FSH), cage subsidence, and adjacent segment degeneration, were assessed.ResultsThe VAS score, JOA score, and NDI score were significantly improved in both groups. However, the patients in the cage-with-plate group were more likely to have neck pain at the last follow-up. The cervical lordosis, FSC, and FSH showed significant correction immediately after surgery. The loss of the cervical lordosis and FSH were higher in the MC+ group.ConclusionsWe found that use of MC+ cages is safe and effective in treating MCSM, but for patients who require strong postoperative stabilization and maintaining the cervical alignment better, the cage-with-plate fixation may best.

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Background The roles of TMEM206, a new transmembrane protein, in cancer, including colorectal cancer (CRC), are unknown. Related family members, including TMEM16A, TMEM132A, and TMEM176B, have been shown to be involved in various biological behaviors. In addition, TMEM88 has been reported to promote non‐small‐cell lung cancer. In this study, we examined the roles of TMEM206 in CRC. Method Real‐time reverse transcription polymerase chain reaction was used to measure TMEM206 messenger RNA (mRNA) levels in clinical specimens and transfected cell lines. Immunohistochemistry was used to determine the relationship between TMEM206 expression levels and clinical data. Plasmids and small interfering RNA were used to upregulate and silence TMEM206, respectively. Protein expression levels and signaling pathway modulation were validated through western blot analysis. Colony formation, MTT, cell migration and invasion assays, and flow cytometry analyses were used to test the potential roles of TMEM206 in CRC. Co‐immunoprecipitation was used to evaluate the interaction between TMEM206 and AKT. Results Investigation of the clinical significance of TMEM206 expression in CRC tissues revealed that TMEM206 mRNA and protein levels were higher in CRC tissues than in paired normal adjacent tissues (p < 0.05). TMEM206 overexpression was positively associated with T stage of cancer and UICC stage ( p < 0.05) and negatively related to differentiation of CRC ( p = 0.015). Upregulation or silencing of TMEM206 promoted or inhibited the proliferation of CRC cells and positively or negatively regulated the levels of phospho‐AKT and downstream signaling pathway components (phospho‐glycogen synthase kinase 3β and cyclin D1), respectively. Moreover, silencing of TMEM206 in cell lines arrested CRC cells in the G1 stage of the cell‐cycle. In addition, upregulating or silencing TMEM206 increased or decreased cell invasion and migration in vitro and positively or negatively altered levels of the phospho‐extracellular signal‐regulated kinase (ERK) and phospho‐focal adhesion kinase 397, respectively. Co‐immunoprecipitation demonstrated that AKT and TMEM206 proteins interacted. Furthermore, TMEM206 promoted the development and progression of CRC by enhancing the interactions between the AKT and ERK signaling pathways. Conclusion TMEM206 controlled the progression of CRC by accelerating CRC cell proliferation and promoting CRC cell migration and invasion. The target of TMEM206 may be AKT, which is known to be involved in modulating the biological behaviors of various cancers.