Dual Specificity Phosphatase 12 Regulates Hepatic Lipid Metabolism Through Inhibition of the Lipogenesis and Apoptosis Signal-Regulating Kinase 1 Pathways.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Due to the growing economic burden of NAFLD on public health, it has become an emergent target for clinical intervention. DUSP12 is a member of the dual specificity phosphatase (DUSP) family, which plays important roles in brown adipocyte differentiation, microbial infection, and cardiac hypertrophy. However, the role of DUSP12 in NAFLD has yet to be clarified. Here, we reveal that DUSP12 protects against hepatic steatosis and inflammation in L02 cells after palmitic acid/oleic acid treatment. We demonstrate that hepatocyte specific DUSP12-deficient mice exhibit high-fat diet (HFD)-induced and high-fat high-cholesterol diet-induced hyperinsulinemia and liver steatosis and decreased insulin sensitivity. Consistently, DUSP12 overexpression in hepatocyte could reduce HFD-induced hepatic steatosis, insulin resistance, and inflammation. At the molecular level, steatosis in the absence of DUSP12 was characterized by elevated apoptosis signal-regulating kinase 1 (ASK1), which mediates the mitogen-activated protein kinase (MAPK) pathway and hepatic metabolism. DUSP12 physically binds to ASK1, promotes its dephosphorylation, and inhibits its action on ASK1-related proteins, JUN N-terminal kinase, and p38 MAPK in order to inhibit lipogenesis under high-fat conditions. Conclusion: DUSP12 acts as a positive regulator in hepatic steatosis and offers potential therapeutic opportunities for NAFLD.

[Incidence of metabolic syndrome in systemic lupus erythematosus and its influence by glucocorticoids].

OBJECTIVE: To investigate the incidence and correlative factors of metabolic syndrome (MS) in patients with systemic lupus erythematosus (SLE). METHODS: A total of 116 SLE patients and 115 controls were enrolled into the study. The incidence of MS, SLE disease activity index (SLEDAI) of patients with SLE combined with MS (MS-SLE) and patients without MS (n-MS-SLE), lupus characteristics, cumulative glucocorticoids, administration dose of glucocorticoids and hydroxychloroquine were compared between SLE group and the control group. RESULTS: The incidence of MS of SLE group was obviously higher than that of the control (34.48% vs 14.78%, P < 0.05). The ratios of patients with lower HDL-C, higher TG and higher blood pressure in SLE group (50.86%, 56.03%, 46.55%) were higher than those in the controls (34.78%, 16.52%, 20.00%, all P < 0.05). MS-SLE group had significantly higher mean waist circumference, BMI, systolic blood pressure and diastolic blood pressure and lower HDL-C than n-MS-SLE group (all P < 0.05). No significant difference was found regarding duration of disease, renal involvement, ESR, C-reactive protein,high-sensitivity C-reactive protein, SLEDAI, cumulative and current glucocorticoids use in MS-SLE group and n-MS-SLE group. The ratio of patients taking hydroxychloroquine in n-MS-SLE group was higher than that of MS-SLE group (46.05% vs 15.00%, P < 0.05). CONCLUSIONS: Patients with SLE has a higher incidence rate of MS. Hydroxychloroquine may reduce their MS incidence.

Pharmacotherapy for Behçet's Disease and the Risk of Malignancy.

Background: Behçet's disease (BD) is associated with an increased risk of cancer. Few reports have been published on the relationship between drug exposure and the risk of cancer in patients with BD. Herein, we explored the relationship between pharmacologic interventions for BD and the risk of cancer. Methods: we carried out a retrospective nested case-control study in a cohort of BD patients from attending our institution. Among 1,148 patients, 22 cancer patients were individually 1:2 matched to 44 cancer-free controls. The following biochemical indicators were evaluated: routine blood analysis, liver and kidney function tests, inflammatory indexes, blood gas analysis, blood electrolyte and previous pharmacologic interventions to manage BD including systemic glucocorticoids, methotrexate, cyclosporine-A, azathioprine, cyclophosphamide (CYC), and thalidomide, which are considered the primary medicines used for the management of BD. Results: Among the 22 BD patients with cancers, myelodysplastic syndrome (MDS) (22.72%) was the most common type. Furthermore, CYC administration was significantly higher in BD patients with cancer compared with the cancer-free matched control group. Further, we observed that complement 4 (C4) (odds ratio [OR] = 0.0001, 95% confidence interval [CI]: 0.001-0.065) and hemoglobin (Hb) (OR = 0.891, 95% CI: 0.795-0.998) levels were independent protective factors for predicting cancer risk in BD patients on multivariate analyses. Conclusion: Our study revealed that CYC was associated with a high risk of cancer in BD patients. Furthermore, C4 and Hb are independent protective factors for oncogenesis in BD patients. These findings may provide references and suggestions for clinicians to select appropriate treatments and for the early recognition of high-risk patients to reduce cancer incidence in BD patients.

Study on the Mechanism of Acori Graminei Rhizoma in the Treatment of Alzheimer's Disease Based on Network Pharmacology and Molecular Docking.

Alzheimer's disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer's disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of "drug-active ingredient-ingredient target." A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer's disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer's signal pathway, thus reducing the production of Aß, inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor.

Diagnosing relapsing polychondritis remains a common challenge: experience from a Chinese retrospective cohort.

OBJECTIVE: The diagnosis of relapsing polychondritis (RP) is often mistaken or delayed. In this retrospective cohort, we aimed to unveil the causes responsible for such phenomenon, to determine the associated factors, and to compare diagnosis in clinical settings with the current diagnostic criteria. METHOD: Eighty-seven RP patients followed-up by rheumatologists from January 1, 2008, to October 31, 2018, were retrospectively analyzed. RESULTS: A total of 50 male and 37 female patients were included with a mean age of 45.9 ± 14.5 years. Ninety-three percent were initially admitted by non-rheumatologic specialists .Twenty-eight percent were correctly diagnosed, while 72% were misdiagnosed at the first visits, all by non-rheumatologic specialists. Patients admitted by non-rheumatologic specialists had increased odds of misdiagnosis (odds ratio [OR] = 1.3, 95% confidence interval [95% CI] 1.1-1.7, P = 0.000). Fifty-seven (65.5%) patients did not meet with Michet or Damiani criteria, with 16 (18.4%) patients diagnosed as partial RP and 41( 47.1%) patients diagnosed as limited RP. CONCLUSIONS: Incorrect and delayed diagnosis of RP is common in our cohort, and insufficient awareness of the disease in non-rheumatologic specialists at least partially contributes to this. It is imperative to revise the current criteria for early diagnosis.Key Points• Diagnosing relapsing polychondritis (RP) in early stage remains challenging after all these years, especially among non-rheumatologic specialists, indicating the importance of teaching non-rheumatologic specialists to improve their understanding of this rare disease.• Many RP patients did not fully meet with the current criteria, suggesting that revision of the current criteria is imperative for early diagnosis of this rare disease.

[Seroepidemiological survey of Toxoplasma gondii infection among employees in a pork food processing enterprise].

OBJECTIVE: To understand the situation of seroepidemiology of Toxoplasma gondii infection among employees in a pork food processing enterprise in Dongtai City. METHODS: Totally 200 employees from a pork food processing enterprise in Dongtai City were selected as the research objects. The venous blood of the selected population was extracted and the IgG antibody against T. gondii in serum was detected by ELISA, and the results were analyzed. RESULTS: Among the 200 employees, 36 cases were positive in IgG antibody detection, the positive rate was 18.0%. The positive rate of IgG antibody among workers with different length of service was significantly different (χ2 = 9.813, P < 0.05). With the increase of working age, the positive rate of IgG antibody gradually increased. The positive rate of IgG antibody to T. gondii was significantly higher in the population who had frequent contact with animals. CONCLUSIONS: The positive rate of IgG antibody against T. gondii in employees in pork food processing enterprises is high. Therefore, the detection of antibodies against T. gondii and health education should be strengthened in this population.