Construction and validation of a risk prediction model for diabetes mellitus in patients with vitiligo / 中华皮肤科杂志

Objective:To analyze risk factors for diabetes mellitus in patients with vitiligo, and to construct and validate a prediction model.Methods:A total of 110 vitiligo patients with diabetes mellitus (comorbidity group) and 4 505 vitiligo patients without diabetes mellitus (control group) were collected from the medical record database in Xijing Hospital, the Fourth Military Medical University from January 2010 to October 2021, and matched for gender and age at a ratio of 1∶4 by using a propensity score method. After matching, the matched pairs were randomly divided into a training set and a test set at a ratio of 4∶1. Univariate and multivariate logistic regression analyses were used to assess demographic and clinical characteristics of patients in the training set, screen differential factors, and construct a prediction model. A five-fold cross-validation method was used for internal validation after construction of the prediction model. The discrimination (area under the curve [AUC]) , calibration (Hosmer-Lemeshow test) and accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) of the prediction model were evaluated in the test set.Results:A total of 107 cases in the comorbidity group and 428 cases in the control group were successfully matched. The training set included 430 cases, and the test set included 105 cases. Based on multivariate logistic regression results, a total of 6 factors were included in the prediction model, including course of vitiligo (odds ratio [ OR] = 1.04, 95% confidence interval [ CI]: 1.02 - 1.07, P<0.001) , high-sugar/high-fat/high-salt diet ( OR = 3.19, 95% CI: 1.38 - 7.38, P = 0.007) , family history of diabetes ( OR = 23.23, 95% CI: 9.72 - 55.50, P<0.001) , metabolic comorbidities ( OR = 12.53, 95% CI: 5.60 - 28.07, P<0.001) , autoimmune comorbidities ( OR = 5.89, 95% CI: 2.52 - 13.76, P<0.001) , and acral vitiligo ( OR = 3.84, 95% CI: 1.45 - 10.19, P = 0.007) . Five-fold cross-validation results showed a good predictive performance of the prediction model, with the AUC being 0.902 (95% CI: 0.864 - 0.940) in the training set and 0.895 (95% CI: 0.815 - 0.974) in the test set. The prediction model also showed favourable discrimination (AUC =0.814, 95% CI: 0.715 - 0.913) , calibration (Hosmer-Lemeshow test, P = 0.068) , and accuracy (sensitivity = 0.810, 95% CI: 0.574 - 0.937; specificity = 0.786, 95% CI: 0.680 - 0.865; positive predictive value = 0.486, 95% CI: 0.317 - 0.657; negative predictive value = 0.943, 95% CI: 0.853 - 0.982) in the test set. Conclusion:A risk prediction model was constructed for diabetes mellitus in patients with vitiligo based on 6 factors (course of vitiligo, high-sugar/high-fat/high-salt diet, family history of diabetes, metabolic comorbidities, autoimmune comorbidities, and acral vitiligo) , which showed favourable discrimination, calibration and accuracy, and might provide a reference for screening the high-risk diabetic population in vitiligo patients.

Activating transcription factor 6-C/EBP homologous protein pathway mediates advanced glycated albumin-induced macrophage apoptosis / 生理学报

The purpose of this study was to investigate whether activating transcription factor 6 (ATF6), a sensor to endoplasmic reticulum stress (ERS), would mediate advanced glycated albumin (AGE-alb)-induced macrophage apoptosis and to elucidate the possible molecular mechanisms. RAW264.7 macrophages were cultured in vitro and treated with AGE-alb (2, 4 and 6 g/L), normal control albumin or tunicamycin (TM, 4 mg/L) for 24 h. ATF6 small interfering RNA (siRNA) was transfected to RAW264.7 cells by Lipofectamine 2000. Cell viability and apoptosis were determined by MTT method and Annexin V-FITC/propidium iodide apoptosis detection kit, respectively. The activities of lactate dehydrogenase (LDH) in medium and caspase-3 in cells were measured by corresponding detection kits. ATF6 nuclear translocation was detected by Western blot and immunofluorescence cytochemistry. Protein and mRNA levels of C/EBP homologous protein (CHOP, a key-signaling component of ERS-induced apoptosis) were detected by Western blot and real-time fluorescence quantitative PCR, respectively. The results showed that similar to TM, AGE-alb increased the expression of CHOP at both the protein and mRNA levels in a concentration dependent manner. ATF6, as a factor that positively regulates CHOP expression, was activated by AGE-alb in a concentration dependent manner. siRNA-mediated knockdown of ATF6 significantly inhibited AGE-alb-induced macrophage injury, as indicated by the increased cell viability and the decreased LDH release, apoptosis and caspase-3 activation. Additionally, ATF6 siRNA attenuated AGE-alb-induced CHOP upregulation at both the protein and mRNA levels. These results suggest that ATF6 and its downstream molecule CHOP are involved in AGE-alb-induced macrophage apoptosis.

Allicin attenuates macrophage-derived foam cell apoptosis by inhibiting caspase-12 / 中国病理生理杂志

AIM:To investigate the inhibitory effect of allicin on apoptosis and caspase-12 activation of macro-phage-derived foam cells,and to elucidate the underlying molecular mechanisms. METHODS:RAW264.7 macrophages were pretreated with allicin (12.5,25 and 50 mg/L) or 4-phenylbutyric acid(PBA,4 mmol/L) for 1 h and then treated with oxidized low-density lipoprotein(ox-LDL,100 mg/L) or tunicamycin(TM,4 mg/L) for 24 h. The cell viability and apoptosis were examined by MTT assay and flow cytometry with Annexin V-FITC/PI staining,respectively. The activities of caspase-3 in the cells and lactic dehydrogenase (LDH) in the medium were measured. The protein levels of caspase-12 were determined by Western blot. The intracellular lipid accumulation was measured with oil red O staining and the content of intracellular total cholesterol was determined by enzymatic colorimetry. RESULTS:Similar to the endoplasmic reticulum stress (ERS) inhibitor PBA, allicin inhibited ox-LDL-induced injury of RAW264.7 macrophages in a concentration-de-pendent manner,as determined by the increased cell viability and the decreased LDH leakage,apoptosis and caspase-3 ac-tivity. The decrease in cell viability and increases in LDH leakage and apoptosis induced by TM (an ERS inducer) were also suppressed by allicin. Moreover, similar to PBA, allicin remarkably inhibited ox-LDL- or TM-induced activation of caspase-12. Furthermore, allicin remarkably attenuated ox-LDL-induced lipid accumulation in the RAW264.7 cells and foam cells formation in a concentration-dependent manner. CONCLUSION:Allicin may inhibit macrophage-derived foam cell apoptosis induced by ox-LDL,and the mechanism is partially related to suppressing the activation of caspase-12.

The pilot study on the expression of PHF8, H3K9me2, BDNF and LTP in the hippocampus of rats exposed to aluminum / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>In this research, we have observed changes of PHF8、H3K9me2、BDNF, and their regulatory roles in changing the amplitude value of LTP in hippocampus due to aluminum exposure so that we can discuss the impact on the learning and memory that caused by chronic aluminum exposure.</p><p><b>METHODS</b>Forty healthy SPF grade SD male rats were randomly divided into four groups by weight, including control group and low, medium, high dose aluminum exposed group, each group had 10 rats. The exposed rats drank water containing different doses of aluminum chloride (AlCl3) (2、12、72 mg/kg Al(3+)) for 90 d. We measured LTP in hippocampus by electrophysiological grapier and detected the expression of PHF8、H3K9me2、BDNF by western-blot.</p><p><b>RESULTS</b>Electrophysiological measurements shows that compared with that of control group, the average of fEPSPs was decreased at different time points in all exposed groups (P<0.01) . The results of western-bolt test demonstrated that the expression of PHF8 in the exposed groups were significantly lower than those of control group (P<0.01) . And the expression the of H3K9me2 of medium and high dose groups were significantly higher than control group (P<0.05) . While the expression of BDNF of medium and high dose groups were decreased compared with the control group (P<0.05) .</p><p><b>CONCLUSION</b>Chronic aluminum exposure can reduce the LTP via the route of PHF8-H3K9me2-BDNF in the hippocampus of rats, which then may impair the ability of learning and memory.</p>

The study on the relationship between hippocampus neuronal apoptosis and hippocampus synaptic plasticity in rats exposed to aluminum / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of aluminum exposure on neuronal apoptosis of rats hippocampus and the correlation of and synaptic plasticity.</p><p><b>METHODS</b>There were 40 SPF grade SD rats which were randomly divided into four groups: the control group, the low dose group, the medium dose group and the high dose group, 10 rats in each group. The rats were daily gavaged with aluminum lactate for 30 days. The hippocampal fEPSPs in rat was measured by electrophysiological grapher and the neuronal apoptosis in hippocampus was detected by Flow cytometer. In addition, the relative expression of gene which includes caspase-3, 8, 9 was measured by Real-time PCR.</p><p><b>RESULTS</b>Compared to the control group, the average of fEPSPs which after HFS 10, 20, 30, 40, 50, 60 min was decreased at different time point in the low dose group, the medium dose group and the high dose group (P < 0.05). Compared with the control group, the rate of apoptosis was significantly increased in the medium dose group and the high dose group (P < 0.05). Compared to the control group, the relative expression of caspase-3 in the medium dose group and the high dose group was significantly increased in Real-time PCR (P < 0.05), and the relative expression of caspase-8 in the high dose group was significantly increased (P < 0.05).</p><p><b>CONCLUSION</b>Aluminum exposure may induced neuronal apoptosis in rats, and then affect hippocampal synaptic plasticity.</p>