High‐fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD‐fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+DX5– tissue‐resident NK (trNK) cells. Obesity‐induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD‐fed mice. OPN treatment enhances the expression of ER stress markers, including p‐PERK, p‐eIF2, ATF4, and CHOP in both murine liver tissues and HL‐7702, a human liver cell line. Pretreatment of HL‐7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate‐1 (IRS‐1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity‐induced hepatic ER stress, and IR through OPN production.

Rationale:Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a small subtype of T-cell acute lymphoblastic leukemia with a typical immune-phenotype: lack of T-lineage cell surface markers CD1a and CD8 expression, weak or absent CD5 expression, at least one of the myeloid or hematopoietic stem cell markers. It is characterized by high rate of induction failure and the effective unified treatment strategies are still indeterminate. We present 2 ETP-ALL cases.Patient concerns:A 42-year-old man presented with abnormal hemogram for 4 months, intermittent fever for 2 months and cough for 1 week. A 27-year-old woman was admitted to the hospital for a fever and headache for that had persisted for 1 week.Diagnosis:The peripheral blood examination, the bone marrow aspiration and flow cytometry for both patients revealed ETP-ALL.Interventions:Both cases accepted chemotherapy including cytarabine.Outcomes:In case one, the patient reached complete hematological remission with negative minimal residual detected by flow cytometry after the first circle of chemotherapy. In case 2, the patient received complete remission after the second circle of chemotherapy with high doses of cytarabine.Lessons:The application of the high-dose cytarabine in induction chemotherapy of ETP-ALL can bring better outcome. ETP-ALL with myeloid features may benefit from therapies used in myeloid malignancies.

Kawasaki disease (KD) is an acute, self-limited inflammatory illness during childhood that may lead to thrombosis in the coronary arteries (CA). The major aims of the present study were to estimate the serum levels of long non-coding RNAs (lncRNAs) and the metabolic profiles of patients with KD. A total of 40 specimens were obtained from pediatric patients (40 specimens before and 40 specimens after treatment) who were diagnosed with KD (n=40). The controls comprised healthy children without KD (n=40). The serum levels of lncRNAs steroid receptor RNA activator (SRA), human leukocyte antigen complex group 22 (HCG22) and myosin heavy chain-associated RNA transcript (MHRT) were determined using reverse transcription-quantitative PCR. Subsequently, the correlation between the expression levels of lncRNAs and biochemical parameters of patients was assessed. Receiver operating characteristic curves were constructed to determine the diagnostic value of the lncRNAs. The results indicated that the serum levels of lncRNAs SRA and HCG22 were higher in patients with acute KD compared with those in healthy controls. B-type natriuretic peptide (BNP) and C-reactive protein were positively correlated with HCG22 in patients with acute KD, while total cholesterol and low-density lipoprotein were negatively correlated with HCG22 in patients with acute KD. The lncRNA MHRT was significantly upregulated in convalescent KD compared with acute KD following intravenous immunoglobulin therapy. In patients with convalescent KD, creatine kinase was positively correlated with MHRT, while BNP and adenosine deaminase were negatively correlated with MHRT. In conclusion, to the best of our knowledge, the present study was the first to identify that the serum levels of lncRNAs SRA and HCG22 in patients with acute KD were higher compared with those in control subjects. MHRT levels in patients with convalescent KD were higher than those in the acute phase. LncRNAs SRA and HCG22 may have crucial roles in KD and are potential novel diagnostic biomarkers for KD. LncRNA MHRT may be considered a novel biomarker for predicting the clinical prognosis of patients with KD.

The prevalence of cardiovascular disease (CVD) is higher in patients with schizophrenia than in the general population. We aimed to investigate whether atypical antipsychotics (AAP) increase the levels of lipoprotein-associated phospholipase A2 (Lp-PLA2), thereby increasing the risk of CVD. The data were from inpatients aged 18-60 years with a diagnosis of schizophrenia according to ICD-10 at the Affiliated Brain Hospital of Nanjing Medical University who underwent physical examination between 1 October 2014 and 30 September 2016. A retrospective cohort study was used to analyse the correlation between AAP, Lp-PLA2 levels and the CVD risk (it was determined that Lp-PLA2 values >200 ng/mL were defined as high CVD risk) in patients treated with monotherapy, olanzapine, clozapine or quetiapine. Data were collected for 452 patients with eligible schizophrenia: 163 treated with clozapine, 186 treated with olanzapine, 47 treated with quetiapine and 56 receiving no medication. Compared with the no-medication patients, AAP administration in patients with olanzapine, clozapine or quetiapine had higher serum Lp-PLA2 levels when age, sex, BMI and fasting glucose level were matched. AAP were significantly associated with serum Lp-PLA2 level by Spearman's correlation coefficients. The results of logistic regression analysis showed that AAP administration was an independent factor of CVD risk when adjusted by potential confounding factors. This study is the first to confirm that AAP administration, especially clozapine and olanzapine, could increase Lp-PLA2 levels and CVD risk, independent of drug-induced weight gain in schizophrenia. The extent and the factors of increasing Lp-PLA2 level and CVD risk in olanzapine, clozapine and quetiapine are discrepant. The possible effects of AAP on Lp-PLA2 in schizophrenia patients are involved in pro-inflammatory cytokines and hormones.