Purpose: Osteocyte network structure correlates with bone material quality. This network is profoundly altered in diabetic mice; however, the underlying mechanisms are unknown. The gap junction protein connexin 43 (Cx43) is necessary for normal osteocyte function and osteocyte network formation. Here, we evaluated Cx43 expression in patients with diabetes, the effect of high glucose on Cx43 expression, and the function of Cx43 gap junctions and hemichannels in osteocyte-like MLO-Y4 (MLO-Y4) cells. Patients and Methods: Human cortical bone samples were obtained from patients with or without type II diabetes mellitus (T2DM) who underwent arthroplasty surgery to treat osteoporosis-induced femoral neck fracture. Cx43 expression was quantified in human cortical bone samples from both groups of patients and MLO-Y4 cells. The functions of Cx43 gap junctions and hemichannels in MLO-Y4 cells were evaluated using dye transfer and dye uptake assays, respectively. Furthermore, we evaluated levels of membrane Cx43 (mCx43), the functional form, and p38MAPK/ERK1/2 signaling, which is involved in mCx43 internalization, to characterize the mechanism of decreased Cx43 expression and gap junctions and hemichannels function. Results: Osteocyte Cx43 expression was decreased in femoral neck cortical bone samples of patients with T2DM patients compared with the non-diabetic control group. In addition, Cx43 expression was decreased in MLO-Y4 cells treated with high glucose. The functions of Cx43 gap junctions and hemichannels were inhibited in MLO-Y4 cells treated with high glucose. mCx43 expression was decreased in response to activation of p38-MAPK/ERK signaling. Inhibition of the p38-MAPK/ERK pathway partially reversed the decreases in Cx43 hemichannels and gap-junctions function. Conclusion: High glucose dampened Cx43 gap junction and hemichannel function in MLO-Y4 cells by activating the p38MAPK/ERK pathway leading to subsequent mCx43 internalization.

Background Acute kidney injury (AKI) is a common and critical complication of sepsis, and is associated with unacceptable morbidity and mortality. Current diagnostic criteria for AKI was insensitive for early detection. Novel biomarkers including cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), klotho and fibroblast growth factor-23 (FGF-23) can predict AKI earlier and allow immediate interventions. We aimed to determine the diagnostic performance of these biomarkers for detecting AKI in sepsis patients. Methods This prospective observational study was conducted between May 2018 and November 2020, enrolling 162 sepsis patients eventually. The AKI was defined in accordance with 2012 KDIGO criteria and we divided patients into non-AKI (n = 102) and AKI (n = 60) groups. Serum levels of several AKI biomarkers were detected by ELISA. The relationship between biomarker levels on admission of AKI was analyzed and discrimination performances comparison were performed. Results AKI incidence was up to 37.0% (60/162) during hospitalization. Compared with non-AKI group, both serum cystatin C, KIM-1, NGAL and FGF-23 were significantly elevated at admission in septic AKI patients. The areas under the receiver operating curves demonstrated that serum cystatin C had modest discriminative powers for predicting AKI after sepsis, and cystatin C combined with serum creatinine in the prediction of septic AKI increased the diagnostic sensitivity prominently. Conclusion Serum cystatin C, KIM-1, NGAL and FGF-23 levels were both increased in septic AKI patients. Our study provided reliable evidence that cystatin C solely and combined with serum creatinine may accurately and sensitively predict septic AKI of patients on admission.

Background TAFRO syndrome is a clinical subtype of idiopathic multicentric Castleman disease (iMCD) that is characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis (or renal dysfunction), and organomegaly. TAFRO syndrome has only recently been described, and many clinicians are unaware of this disease, leading to delays in diagnosis and treatment. We present two patients with TAFRO syndrome in whom renal biopsies were performed. Case presentation Both patients had subacute onset and exhibited renal insufficiency, edema, anemia, thrombocytopenia, polyserositis and lymphadenopathy over the disease course. However, there were many differences in their clinical manifestations. Case 1 was a 30-year-old woman admitted due to intermittent vaginal bleeding for 3 weeks. Laboratory tests on admission showed severe renal insufficiency (creatinine: 624 μmol/L), severe anemia (Hb: 41 g/L), and moderate thrombocytopenia (61 × 109/L). Case 2 was a 42-year-old man. Acute epigastric pain was his initial complaint, and computed tomography (CT) revealed retroperitoneal exudation around the pancreas. He was diagnosed with acute pancreatitis, and after treatment with a proton pump inhibitor (PPI) and somatostatin, his abdominal pain still recurred. During treatment, renal failure gradually increased, with oliguria, fever, anemia, thrombocytopenia, edema and massive ascites. Lymph node histologies were consistent with the hyaline-vascular (HV) type and mixed type, respectively, and renal histopathologies were consistent with thrombotic microangiopathy (TMA)-like renal lesions and membranoproliferative glomerulonephritis (MPGN), respectively. Their general conditions improved after glucocorticoid therapy, but their renal functions did not recover completely. On the basis of glucocorticoids, second-line treatments with tocilizumab and rituximab, respectively, were applied. Conclusions The diagnosis of TAFRO syndrome is based mainly on clinical manifestations and lymph node biopsies. A reliable early diagnosis and appropriate rapid treatment are essential to improve patient outcomes. Clinicians should deepen their understanding of this disease and similar conditions. Once the disease is suspected, lymph node biopsies should be performed as soon as possible. In addition, renal biopsies should be actively performed in patients with renal involvement.

The aim of this study was to explore the impact of depression mood disorder on the incidence of adverse drug reactions of anticancer drugs in cancer patients. The Hamilton Depression Scale 17 was used to evaluate the depression mood disorder level in 73 cancer patients before chemotherapy. Pharmacists monitored adverse drug reactions during the chemotherapy period. The relationship between depression mood disorder level and the incidence of adverse drug reactions was analysed. The frequency and extent of total adverse drug reactions were not related to depression mood disorder level. The frequency and extent of subjectively experienced adverse drug reactions such as anorexia, nausea and fatigue were related to depression mood disorder level. In conclusion, psychological support and intervention should be provided to cancer patients in order to improve patient adherence and cancer chemotherapy effectiveness, and to decrease the incidence of adverse drug reactions.